Top 100 Impactful Papers
Aging and Multimorbidity
2023
Loneliness is associated with frailty over time in older men living with and without HIV
Innovation in Aging
The study looked at how feeling lonely and being frail are connected over a period of 2 years among middle-aged and aging sexual minority men, whether they have HIV or not. They found that if a person felt lonely at the beginning, they were more likely to become frail two years later, but the opposite didn't show - being frail at the start didn't make someone more likely to feel lonely later. This suggests that loneliness might come before frailty, and checking for loneliness early and often could help prevent frailty in sexual minority men with and without HIV.
IMPACT
This research may influence healthcare strategies to enhance the overall well-being of this demographic, emphasizing the importance of addressing social factors in preventing health issues.
2021
Prefrail and frail women with and without HIV are more likely to experience falls
JAIDS
Middle-aged PWH appear to have unexpectedly high rate of falls which is similar to people without HIV who are decades older. We found that compared to robust women, prefrail and frail women with and without HIV were more likely to experience single or recurrent falls over a one year time period. Our study suggests that prefrailty is very common and may be potential intervention target to reduce the risk of falls in women aging with and without HIV.
IMPACT
This study identifies prefrailty as a highly prevalent and potentially modifiable intervention target to prevent falls in women with and without HIV.
2021
Women with HIV have a higher burden of aging-related non-AIDS comorbidities than women without HIV
Clinical Infectious Diseases
Persons with HIV are aging and increasingly at risk of chronic conditions such as heart and kidney disease. Women have historically been underrepresented in HIV research, including research on aging. We found that women with HIV have a higher burden of comorbidities than women without HIV, overall and in certain age groups. Comorbidity burden among women with HIV was associated with traditional but not HIV-related risk factors. These findings suggest that novel strategies for comorbidity screening and prevention are needed among women with HIV that incorporate traditional factors such as substance use and social determinants of health.
IMPACT
This publication has been broadly cited (52 to date) including in high impact journals such as CID, AIDS, JAMA network, etc. and has been impactful in bringing to light the importance of focusing on women with HIV at the intersection of aging and multimorbidity, including sex and gender specific mechanisms for disease burden (eg, menopause, exacerbated social determinants of health) as potential targets of multimorbidity risk assessment and intervention.
2018
Inflammation related immune response to cytomegalovirus (CMV)
J. Infect. Dis.
In this study circulating markers of inflammation were measured in 42 men in the MACS, along with the magnitude of T-cell responses to cytomegalovirus, to see if T-cell responses could explain the degree of inflammation in these men. Significant correlations were found between the T-cell responses and several markers of inflammation, and these correlations were different between men who were frail and men who were not frail. These data suggest that a good deal of the residual inflammation that is present in people living with virologically suppressed HIV, and which is associated with increased risk of chronic and aging-related comorbidities, may be due to CMV infection, and that treatment of CMV may improve long-term health of such people.
IMPACT
The cause of residual inflammation and immune activation in people living with virologically suppressed HIV infection is one of the major unanswered questions in the care and long-term health of people living with HIV. This study is one of the first to evaluate CMV infection, which is present in the vast majority of people living with HIV, as a possible cause. The publication of this paper had an immediate impact on the field and was one of the most cited papers in J. Infect. Disease in the first year after its publication.
2016
Frailty among women with HIV is related to many non-HIV factors
J Frailty Aging
We showed that among women with and without HIV during midlife (average age 39 years), women with HIV presented with more frailty. There were many factors associated with frailty including HIV status and severity, older age, lower income, current or former smoking, and poorer liver and kidney function. This points to many ways that we can improve the health of women with HIV who are not very well controlled and have aging-related problems as well.
IMPACT
67 citations. JFA has an IF of 3.9. In 2023 we published a similar analysis in JFA among women 13 years later and found different factors related to frailty, showing that understanding the life course of women with HIV is important to identify modifiable risk factors for improving the health of aging women with and without HIV.
2016
Physical and metabolic frailty, and not depression, predicted death within 8 years when women with HIV were average 39 years old
BMJ Open
Women with HIV at middle age were more likely to die within 8 years if they were frail or had biological frailty. Depression was not related to death.
IMPACT
21 citations. BMJ Open has an IF of 2.9. We addressed the controversy over which of 3 commonly used scales in HIV research predict death longitudinally. These scales included the Fried Frailty Phenotype, VACS Index, and CES-D and they were simultaneously evaluated in one model to predict death. Notably, frailty and the VACS Index, not depression, were related to subsequent mortality among women with HIV, which challenged previous literature.
2014
Earlier frailty in men living with HIV
J Gerontol A Biol Sci Med Sci
People are more likely to become frail as they age, but assessment of frailty is difficult and had not been rigorously done in people living with HIV. Using a validated definition of frailty, we found that frailty was more common in men living with HIV, including those who were virologically suppressed, between the ages of 50 and 64 years, and was associated with certain other health conditions. These findings emphasize the importance of evaluating people living with HIV for aging-related health conditions at an earlier age.
IMPACT
This study showed that a validated frailty phenotype widely used in the geriatric literature could also be measured in men living with HIV, and that HIV and comorbidities were associated with frailty as defined by this phenotype, which had not been demonstrated before.
Cancer
2023
Genetic risk of HPV entry and precancer
Cancer Epidemiol Biomarkers Prev
Our study is hypothesis generating and supports the mechanisms of human papillomavirus (HPV) entry by binding with cell receptors. This is one of the first studies to report variants in genes encoding the receptors that were associated with increased odds of cervical pre-cancer in African-American women living with HIV. The findings from this study is important in understanding which genes are involved in the HPV cell entry pathway and how it affects precancer and cancer progression.
IMPACT
This study has the potential to inform how to prevent HPV from entering a cell and transferring its genetic material to the host DNA and has been featured as one of the highlighted articles in the Cancer Epidemiology, Biomarkers & Prevention journal September 1, 2023 (volume 32 #9) issue.
2022
Lung cancer screening criteria inadequate in HIV
J AIDS
Certain people are at increased risk of lung cancer, especially those who have smoked. Healthcare providers use specific criteria to determine who should have lung cancer screening. These criteria were developed in studies of people who did not have HIV infection. This paper shows that people living with HIV may require different criteria to best screen for lung cancer.
IMPACT
This paper was cited by in the "Update to Lung Cancer Screening Guidelines" published in Thoracic Surgery Clinics.
2021
This study determined that guidelines recommending HIV(-) women to discontinue cervical cancer screening at the age of 65 years are not appropriate for most HIV(+) women; albeit the subset of HIV(+) women who do meet the required criteria have risks of cervical precancer/cancer similar to HIV(-) women, and may choose to discontinue
AM J Obstet Gynecol
Most HIV(+) women should continue to have cervical cancer screening past the 65 year old age threshold to end screening in the general population; i.e., based on personalized clinic estimates of patient longevity.
IMPACT
Nearly immediate uptake by US government expert clinical task force re screening and management for HPV-related cancers.
Cardiovascular
2022
HIV viremia predicts progression of coronary atherosclerosis
Atherosclerosis
Narrowings in the heart arteries can be seen on CT scans with a contrast injection. Men with HIV who had detectable HIV virus in the blood were more than twice as likely to develop new or worsening narrowings in the heart arteries than men with HIV without viremia. The amount of narrowing over time was most significant in men with HIV viral load > 500 copies/ml.
IMPACT
It is important to limit detectable HIV viremia to help prevent narrowings in the heart arteries.
2021
Larger heart size in men with HIV than men without HIV
Journal of the American Heart Association
People with HIV may be at increased risk for developing heart failure. Using ultrasound of the heart (echocardiography) we found that men with HIV had slightly larger hearts and pressure in the heart than men without HIV, but here was no difference in the heart pump function.
IMPACT
These early changes in the heart might be markers of increased risk for heart failure in the future for men with HIV.
2021
Differences in heart structure between people with and without HIV on cardiac MRI scans
Eur Heart J Cardiovasc Imaging
Cardiac MRI allows for detailed assessment of the heart structure and function. We found that people with HIV had more diffuse scarring in the heart muscle and a larger atrium (one of the heart chambers) than people without HIV.
IMPACT
Diffuse heart muscle scarring and larger left atrium in the heart might be early markers of increased risk for heart failure in people living with HIV.
2016
No specific antiviral medications used to treat persons with HIV appeared to be associated with a greater risk of blockage in the blood vessels that supply the heart (coronary arteries)
AIDS
Living with HIV is associated with a greater risk of having blockage in the blood vessels that supply the heart (coronary arteries) compared to people without HIV; the reasons for this are unclear. In order to figure out whether HIV itself versus the medications used to treat HIV (antiviral therapy, ART) were more to blame for this effect , we compared the amount and type of heart blood vessel blockage seen among hundreds of men with HIV receiving different types of ART. Over 80% of these men had a suppressed HIV viral load (low or undetectable blood level of HIV). All of the men had specialized scans of their heart that measure the amount and type of blockage (plaque) in the blood vessels that supply the heart (coronary arteries). No specific ART medication or combination of medications were associated with a greater risk or amount of blockage in the heart blood vessels.
IMPACT
These findings support our belief that having a suppressed viral load is more important for heart health among PWH than which specific ART medications are used to suppress HIV.
2015
Even with persistent suppression of HIV, PLWH still have increased cardiovascular risk
Clin Infect Dis
When this paper was written, effective HIV treatment had become available, but it was not known whether treated PLWH continued to have increased risk of heart and blood vessel risk or whether this risk applied if patients took medications. We found that HIV infection was associated with disease in the neck arteries (carotid arteries) that continued to worsen over time. The study concluded that HIV might cause heart and blood vessel disease even in patients living with HIV even if the virus was so suppressed that it could not detected in blood.
IMPACT
The paper was cited in the medical literature over 100 times, as evidence that increased heart and blood vessel disease was observed even among persistently virologically suppressed men/women living with HIV.
2014
Inflammation in the blood is associated with heart artery disease
The Journal of Infectious Diseases
Inflammation in the blood was higher in men with HIV than men without HIV, especially in men with low CD4 cell counts. Higher levels of inflammation in the blood were associated with plaque and narrowings in the heart arteries.
IMPACT
Inflammation is associated with heart artery disease and suggests that limiting inflammation with antiretroviral therapy might help to prevent heart artery diseases . Dr. Tony Fauci showed these results at an HIV meeting that I attended demonstrating the impact of these findings.
2011
Immune cell features of HIV-related cardiovascular disease in patients under antiretroviral treatment
Journal Infect Dis
The immune system is affected by HIV, and immune system cells also create disease in the blood vessels and heart. This study found that patients with HIV had chronic overactivity of their immune system, and that this continued even on effective HIV treatment. The study therefore provides some clues about cells of the immune system that we might try to modify with treatment in order to prevent heart and blood vessel diseases in PLWH.
IMPACT
This article was featured with an editorial and in 2019 was cited as one of the foundational studies in the scientific statement, "Characteristics, Prevention, and Management of Cardiovascular Disease in People Living With HIV: A Scientific Statement From the American Heart Association"
2008
HIV associated with increased cardiovascular risk in men and women
AIDS
This was among the first large studies that showed that PLWH might be prone to have heart and blood vessel diseases. We concluded that this was for two reasons -- first, because they had traditional disease risk factors like smoking, and also, because HIV disease markers like low CD4+ T-cell count also contributed to vascular disease. This study confirmed the basis for studying the risk of heart and blood vascular disease further in HIV, which we continue to do to this day in MWCCS.
IMPACT
Widely cited evidence for an association of HIV with cardiovascular disease, with consistent results between men (MACS) and women (WIHS).
2007
Increased risk for corornary heart disease in low income and overweight men and women living with HIV
Clinical Infectious Diseases
Among men and women living with HIV (PLWH) and receiving anti-retroviral drug treatment (ART), being overweight and having a low income level were associated with increased risk for coronary heart disease. This suggests a need to target PLWH with these characteristics for vascular risk factor screening.
IMPACT
Highly cited study (n = 102 as of April 2024) describing significant cardiovascular risk factors in PLWH.
Cognition
2023
Alzheimer disease biomarkers linked to worse cognition in women with and without HIV
JAMA Network Open
We found that increases in certain Alzheimer Disease markers in blood over one year were related to poorer cognitive function (or brain health) in women with and without HIV age 40 years and older. This was measured in relation to other HIV, social and aging-related disease factors.
IMPACT
The IF for JAMA Network Open is 13.4. These are the first ever published longitudinal data in HIV aging and blood-based Alzheimer Disease biomarkers with and without HIV. We are adding value to both the HIV Aging and the Alzheimer Disease literature among older adults with multiple morbidities.
2021
Effective HIV treatment lowers the risk of developing cognitive impairment
AIDS
Before effective HIV treatments became available, many people with HIV developed cognitive impairment which includes difficulty thinking, learning, and remembering. Although current HIV treatments have lowered the risk and severity of these difficulties, we found that some people with HIV can still experience them, especially if they are also living with other chronic infections like hepatitis B or C. These findings show that more studies are needed to help us understand how life-long infections with HIV and hepatitis affect the brain.
IMPACT
This study was cited by an International HIV-Cognition Working Group in their consensus recommendations for a new approach to classifying cognitive impairment in people living with HIV (Nature Reviews Neurology, 2023.
2021
Cognitive profiles vary in women with HIV
Frontiers of Neurology
Cognitive impairment remains frequent and ranges in severity among virally suppressed (VS) women with HIV (WWH). In 929 VS-WWH and 717 HIV-uninfected women from the Women's Interagency HIV Study, we identified five profiles in which women vary in their cognitive functioning. Variables that distinguished such profiles include: clinic site, age, education, race, illicit substance use, current and nadir CD4 count, duration of effective antiretrovirals, and protease inhibitor use.
IMPACT
This article is in a top journal. These findings are important in highlighting the cognitive heterogeneity of those with HIV.
2020
Atrophy in cortical regions linked to normal and pathological aging
Brain Imaging and Behavior
From the Multicenter AIDS Cohort Study (MACS), 302 men were examined for their the associations between brain volume and cognition from those considered "unhealthy" and the other considered "premature aging." Trajectories to cognitive impairment are the result, in part, of atrophy in cortical regions linked to normal and pathological aging. These findings suggest it is possible to predict unhealthy cognitive aging by seeing patterns of brain loss.
IMPACT
This article is in a top journal. It highlights the relationship between brain structure and cognition in men with HIV.
2020
Cognitive profiles vary in women with HIV
Frontiers of Psychology
We identified clusters of individuals with distinct patterns of change in declarative memory in HIV-positive (HIV+) and HIV-negative (HIV-) women. Among Black HIV+ women, four subgroups emerged: a subgroup with minimal decline, two with accelerated decline, and one with stable but low performance. In Black HIV- women, three subgroups emerged: one with minimal decline and two with accelerated decline. Individuals with accelerated decline were less educated and more likely to have a history of depression.
IMPACT
This article provides a novel statistical modeling technique that can be used in other clinical populations.
2018
HIV+ women men show cognitive disadvantages
Journal of Acquired Immunodeficiency Viruses
Cognitive changes were examined in women and men with and without HIV (The Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS)). HIV+ women also had a higher odds of cognitive impairment compared with HIV+ men. Sex differences were constant over time. Although sex differences are generally understudied, HIV+ women vs men show cognitive disadvantages.
IMPACT
This is a highly cited article in a top HIV journal. It has been cited in 5 HIV-related articles.
2018
cART does not alter the trajectory of cognitive decline in men who were impaired prior to effective therapy
AIDS
In the MACS, including data from 3,701 men with and without HIV, cognitive dysfunction is persistent in HIV-infected men and cART does not alter the trajectory of cognitive decline in men who were impaired prior to effective therapy. This suggests that current cognitive impairment in HIV+ men results from a legacy effect, and from factors other than the HIV itself.
IMPACT
This article is in a high impact journal and it highlights the role of ART on cognitive trajectories in men.
2018
Other medications besides antiretroviral therapy linked to cognitive problems in women with HIV
Journal of Acquired Immune Deficiency Syndromes
Cognitive impairment is a frequent in HIV. People with HIV infection may commonly use nonantiretroviral medications known to cause neurocognitive adverse effects (NC-AE). After a literature review, 79 medications (excluding statins) with NC-AE were identified and reported by Women's Interagency HIV Study participants over a 10-year period (i.e., ∼42,000 visits were studied). HIV infection was associated with NC-AE medication use. HIV infection was associated with NC-AE medication use. Providers should consider the impact of NC-AE medications when evaluating patients with HIV and concurrent neurocognitive symptoms.
IMPACT
This article was published in JAIDS, a leading journal. This study highlighted that other medications besides HIV-related drugs may be producing some of the neurocognitive deficits observed in women with HIV. This has implications for prescribing medications.
2017
Cognitive difficulties remain among HIV+ women despite persistent viral suppression
Neurology
This study examined whether persistent viral suppression affects cognition over time in uninfected (HIV-) women and 3 groups of HIV+ women: those with consistent viral suppression after continuous cART use (VS), those without consistent virologic suppression despite continuous cART use (NVS), and those without consistent virologic suppression after intermittent cART use (Int NVS). On global function, VS women demonstrated lower scores and were more likely to score in the impaired range than HIV- women. These differences persisted over time. VS women demonstrated lower learning and memory scores than HIV- women and lower attention/working memory and fluency scores than HIV- and NVS women. Cognitive difficulties remain among HIV+ women despite persistent viral suppression. In some instances, VS women are worse than NVS women.
IMPACT
This was published in Neurology, a top journal. This article is one of the first to document in women that cognitive problems persist despite viral suppression.
2017
Episodic memory and motor function are more vulnerable to advanced HIV and aging
Lancet HIV
Using longitudinal data from the Multicenter AIDS Cohort Study, a greater than expected effect of ageing on episodic memory and motor function with advanced stages of HIV infection was detected. This cognitive deficit may be caused by damage to the hippocampus and basal ganglia. Older individuals with HIV infection should be targeted for regular screening for HIV-associate neurocognitive disorder, particularly with tests that target episodic memory and motor domains.
IMPACT
This study is one of the more comprehensive ones that specifically examine the interaction of aging with HIV on cognition. It is highly cited.
2016
Cognitive profiles vary in men with HIV
AIDS
This study examined whether there were different cognitive profiles in those from the Multicenter AIDS Cohort Study (MACS). Three profiles were founds. For those in Profile 1, they performed below average on all cognitive domains. For those in Profile 2, they performed average on executive functioning, motor, and speed and below average on learning and memory. For those in Profile 3, they performed at or above average across all cognitive domains.
IMPACT
This article is in a high impact journal. It is an important article that highlights various patterns of cognition in men with HIV.
2016
HAND is not progressive in most people with HIV
Neurology
In the Multicenter AIDS Cohort Study (MACS), 33% met the criteria for HIV-Associated Neurocognitive Disorder (HAND). Over the 4-year study, 77% HIV+ individuals remained at their same cognitive level, 13% showed cognitive deterioration, and 10% showed cognitive improvement. Hypercholesterolemia was associated with HAND progression. HAND remains common in HIV+ individuals. However, for the majority of HIV+ individuals, HAND was not a progressive condition over 4 years.
IMPACT
This study was published in Neurology, a top journal. It has also been highly cited (+200).
2015
The effect of HIV on cognition in women is very small
Neurology
In the WIHS, we examined the association between HIV status and cognition. The effect of HIV status was smaller than that of years of education, age, race, income, and reading level. HIV biomarkers (CD4 count, history of AIDS-defining illness, viral load) were associated with cognitive dysfunction. The effect of HIV on cognition in women is very small except among women with low reading level or HIV-related comorbidities.
IMPACT
This article was published in Neurology, a top journal. This article really highlights that HIV itself exerts small direct effects on cognition, but instead, social determinants of health should be considered.
2009
HIV infection may not be the most important predictor of cognition
Neurology
In the MACS, predictors of cognition were examined. HIV serostatus was not significantly associated with poorer cognitive test performance. However, among the HIV-infected individuals, the presence of detectable HIV RNA in plasma was linked to lower memory performance. Medical factors associated with normal aging are significantly associated with performance on cognition.
IMPACT
This study is in Neurology, a top journal; it has also been highly cited.
2001
CNS infections decreased after the introduction of highly active antiretroviral therapy (HAART)
Neurology
This study examined the temporal trends in the incidence rates of HIV dementia and opportunistic CNS disease January 1990 to December 1998 in the Multicenter AIDS Cohort Study. The incidence rates for HIV dementia, cryptococcal meningitis, and lymphoma decreased following the introduction of highly active antiretroviral therapy (HAART). The proportion of new cases of HIV dementia with a CD4 count in a higher range (i.e., 201 to 350) since 1996 may be increasing.
IMPACT
This article is a seminal article in Neurology, a top journal. It has been highly cited (+550).
1996
Psychomotor slowing in HIV is a predictor of dementia, AIDS, and death
Journal of Neurovirology
In men at the Baltimore site of the Multicenter AIDS Cohort-Study (MACS), sustained decline in psychomotor performance in HIV infection was predictive of dementia, AIDS, and death. This brief cogntive battery may be useful for early detection of HIV+ individuals with a poorer prognosis.
IMPACT
This was an early seminal study during a time when there were few medications to treat HIV. This article has been highly cited.
COVID
2023
PLWH have lower antibodies and greater inflammation from the COVID-19 vaccines
The Journal of Infectious Diseases
It is known that people living with HIV respond with lower levels of antibodies following vaccination with other vaccines. We sought to test if this was true of the SARS-CoV-2 vaccines, and find other factors that are involved with the COVID-19 vaccines. We measured antibodies and their properties in men with HIV from the Pittsburgh Clinical Research Site of the MWCCS and found that vaccinated men with HIV indeed have slightly lower levels of antibodies against COVID-19. We also found that men with HIV have a higher activation of pro inflammatory aspects of antibodies, and that HIV virus and antibodies against an HIV protein decrease following vaccination. These results tell us that although men with HIV have less anti-COVID-19 antibodies, the ones they do have may be able to compensate by increasing inflammation. We still are investigating if this inflammation or affects on the HIV virus pose any benefit or risk to patients.
IMPACT
This paper is one of the first to describe the effect of a vaccine on the complement system, especially in patients with HIV. This knowledge has the potential to improve our understanding of how vaccines and immunotherapies behave in people living with HIV, and may shape future booster vaccinations in this particular group.
2021
Social disruptions during the COVID-19 pandemic linked to negative mental health outcomes
Journal of Acquired Immune Deficiency Syndromes
The COVID-19 pandemic caused major social disruptions. Looking at participant data from MWCCS, we found that people with higher levels of social disruption during the COVID-19 pandemic had a higher risk of depression, anxiety, and dissatisfaction with their social support compared to people with lower levels of social disruption. In the aftermath of the COVID-19 pandemic, we need effective structural and social interventions to address mental health needs among the most vulnerable populations.
IMPACT
One of the first studies to explore at the joint MWCCS cohort, this provided a blueprint for full-cohort research work and demonstrated significant mental health sequelae associated with the COVID-19 pandemic.
Diabetes and Adiposity
2022
Women with and without HIV with increasing BMI and leptin levels over 10 years, between age 40 and 50 years, are at risk for worse cognitive function
J Clin Endocrinol Metab
Many older women with and without HIV also have overweight and obesity, and that is related to poorer quality of life and general health. This paper showed that increases in blood markers related to obesity and obesity based on body weight and height are related to how women with and without HIV 'think', even after after 10 years. We should do something about obesity that may be good for better thinking as women with and without HIV get older.
IMPACT
This paper was published in JCEM, which has an IF of 6.13, has 5 citations, and it is a longitudinal, translational approach, bridging the gap between HIV and other scientific disciplines, in this case, Endocrinology, Obesity, Aging, and cognitive health.
2022
Abnormal glucose metabolism was associated with declines in gait speed and grip strength regardless of HIV serostatus
AIDS
People with HIV have more more rapid declines in grip strength and gait (walking) speed compared to people without HIV. In people without HIV, diabetes and elevated blood sugars have been associated with declines in grip strength and gait speed, but this hasn't been well studied in people with HIV. We found that abnormal glucose metabolism (diabetes or elevated blood sugar) was associated with declines in gait speed and grip strength regardless of HIV status. These findings suggest that better control of blood sugars should be studies as a potential way to prevent decline in grip strength or gait speed.
IMPACT
N/A
2018
HIV disease and diabetes interact to affect brain health and cognition
AIDS
The present study investigated the relationship between white matter hyperintensities (WMHs) among people with HIV. WMH are areas on MRI scans that indicate possible damage to brain tissues. MRI scans were done in 322 men in the Multicenter AIDS Cohort Study. There were no significant associations between WMHs and HIV disease. WMHs was predicted by age more than 60, non-white race, kidney function, and diabetes. The combination of HIV and diabetes was significant. Researchers found diabetes has a specific impact among those with HIV, but not uninfected men. This suggests the need for more aggressive treatment even in the prediabetes state, especially as WMHs affect cognitive functions.
IMPACT
This article is in a high impact journal. It has also been cited in 25 HIV-related articles also in high level journals.
2016
The presence of greater amounts of VAT and lower SAT may contribute to increased risk for coronary artery disease among HIV-infected persons
Open Forum Infectious Diseases
Computed tomography (CT) scanning looking for for coronary artery (blood vessels that supply there heart muscle) calcium (CAC) scoring was performed on participating men from the MACS, and, for men with normal kidney function, coronary CT angiography (CTA, use of dye injected through a vein to take pictures of blood flow through the coronary arteries) was also performed. Associations between bodily fat amount (visceral adipose tissue [VAT which is fat deep in the abdomen)], abdominal subcutaneous adipose tissue [aSAT, fat which is under the skin in the abdomen and not as deep as muscle], and thigh subcutaneous adipose tissue [tSAT, fat which is under the skin in the thigh and not as deep as muscle]) with coronary artery blockage presence and extent were assessed with statistical analysis. Results. Among men with HIV (n = 597) but not men without HIV (n = 343), having greater amount of VAT was associated with noncalcified (soft) plaque presence. Men with HIV had lower amounts of aSAT and tSAT and greater amount of VAT than men without HIV. Among men with HIV, having lower amount of aSAT was associated with greater extent of total plaque. Lower tSAT was associated with greater amount of CAC and and overall plaque in both men with HIV and men without HIV. Conclusions: The presence of greater amounts of VAT and lower SAT may contribute to increased risk for coronary artery disease among persons with HIV.
IMPACT
Unknown
2014
Measure of sugar control not accurate in men with HIV
Journal of Antimicrobial Chemotherapy
Hemoglobin A1c is a common test to diagnose diabetes and to see how well treatment is working. We found that, in men with HIV, hemoglobin A1c was lower than expected based on the blood sugar. We also found that the accuracy of this test got worse as the sugar increased. Certain HIV medications and red blood cell features were also related to how inaccurate hemoglobin A1c was. These findings suggest that this measurement may not be a good test in people with HIV.
IMPACT
This study was cited in the 2020 update of the Primary Care Guidelines of the HIV Medicine Association of the Infectious Disease Society of America, as well as a consensus conference from a leading international kidney organization (KDIGO).
2006
A novel pattern of lipoaccumulation involving a nearly circumferential distribution of lipohypertrophy extending from the mid-chest around to the back
JAMA
A unique pattern of fatty tissue in men with HIV on HAART involving a enlarged breast tissue extending the chest around to the back.
IMPACT
Photograph and unique patter of lipodystrophy cited in other publications.
2005
HIV medications linked to insulin resistance
AIDS
HIV protease inhibitors were shown to lead to diabetes in people with HIV soon after combination antiretroviral therapy became available. It was unclear whether other HIV medications were linked to sugar problems. We found that insulin resistance (a condition where the body has trouble processing sugar) was more common in men with HIV and was related to the HIV drug class, nucleoside reverse transcriptase inhibitors (NRTIs).
IMPACT
This study was cited in the HIV Medicine Association Primary Care Guidelines and a consensus statement from the American Heart Association.
2004
HIV seropositive men receiving HAART had diminished body size and higher frequency and severity of body habitus abnormalities, particularly lipoatrophy, compared with the 314 HIV seronegative men
CID
We undertook body measurements a of 530 HIV-positive and 314 HIV-negative men in the Multicenter AIDS Cohort Study at a regular visit that occurred between 1 April and 30 September 1999. We found body size and shape differences that were independent of age: the 384 HIV positive men receiving HAART had diminished body size and higher frequency and severity of body shape abnormalities, particularly fat loss, compared with the 314 HIV negative men.
IMPACT
Cited in many manuscripts describing HIV-associated body habits changes.
Early HIV Medicine
1997
CD38 expression on CD8+ T-cells can be used to predict clinical progression towards AIDS in people living with HIV
J Acquir Immune Defic Syndr Hum Retrovirol
CD8+ T-cells kill HIV-infected cells but after years of battle they can become exhausted and express higher levels of a protein called CD38. The amount of CD38 expressed on CD8+ T-cells predicts how fast a person living with untreated HIV will progress to AIDS and/or death. This finding has led to treatments to improve immune responses to both viral infections, like HIV, and to cancer.
IMPACT
Not only did this study provide a method of predicting the clinical progression to AIDS, but it led to a new understanding that exhaustion of the immune system plays an important role in the body’s ability to eradicate viruses or cancer and opened an entirely new field of research focused on reversing immune exhaustion.
1995
Quantifying intracellular viral RNA is of potential prognostic value in HIV infection
Journal of virology
How quickly HIV progresses can be very different in people with this infection. In this study, we studied ten men with HIV infection who progressed at very different rates. We found that the men with lower CD4 T cells and worsening infection had higher levels of genetic material of HIV called RNA in the blood compared to men with HIV infection but remained stable. This was important to show that measuring RNA levels in the blood (viral load) could be a way to monitor HIV infection.
IMPACT
Analysis of cell-associated unspliced and multiply spliced viral mRNA can determine the extent of the viral reservoir, whether it is being renewed, and the length of time cells containing replication-competent proviral DNA remain.
1995
Among men with HIV, median survival after the first CD4+ cell count or = 2 years
JID
This analysis investigated men with HIV who had very low CD4 cell (T helper) count (< 50 ) survived at a time period when effective therapy was not yet available. Median survival after the first CD4 or = 2 years. Longer survival was associated with receiving the antiviral medication acyclovir and using the anti-HIV medication zidovudine (AZT), having a higher red blood cell (hemoglobin > or = 12) , and working full-time employment. Other factors associated with longer survival included being African-American, no prior AIDS illness, weight loss of less than 4.5 kg (about 10 pounds), and zidovudine use (with or without concurrent acyclovir) after CD4 fell to < 50. . Survival once CD4 fell below 50 may be longer for persons with a good performance status and specific other traits.
IMPACT
Substantial number of citations in peer-reviewed publications.
1992
Among men with HIV, early treatment with zidovudine and PCP prophylaxis improves survival in addition to slowing the progression to AIDS
NEJM
Background: Zidovudine (AZT) has been shown to extend lifespan in persons with AIDS or HIV, and to delay the time to AIDS in the latter
IMPACT
Widely cited, including in guidelines of the time.
Early HIV Pathogenesis
1999
Changes in HIV related to immune decline in men with untreated HIV
J. Virology
HIV evolves over time due to viral mutations and immune selection. This study demonstrated three phases of this evolution: an early phase of linearly increasing viral diversity and divergence from the initially transmitted virus; an intermediate phase with stabilization or decline in diversity; and a late phase with slowdown or stabilization of divergence. The findings provided strong evidence that states of HIV evolution were closely related to immune health in people with typical progression of HIV disease.
IMPACT
This paper led to a better understanding of stages of HIV infection from seroconversion to the development of AIDS, and helped focus studies on the mechanisms underlying onset of these stages. It has been cited more than 1100 times.
1999
Shorter survival in advanced HIV infection is linked to T cell activation
The Journal of Infectious Diseases
It is important to understand what factors predict survival in people with advanced HIV infection. We studied various immune system measurements and virus burden to see what factors were related to survival in men who already had advanced HIV infection and CD4 T cell counts less than 50 cells/mm3. We measured higher levels of a protein called CD38 on the lymphocytes of men who had lower survival, and this indicates that those with a more active immune system (called immune activation) had lower survival.
IMPACT
This work demonstrated that immune activation is a major determinant of survival in advanced HIV-1 disease.
1998
These results identify the first site in the CCR5 promoter that may be a useful target for treatment of HIV-1 infection
The Lancet
This study found that CCR5 molecule on the surface of CD4 T cells is important in HIV-1 pathogenesis. Several naturally occurring variations of CCR5 are less protective. These results identify the first site in CCR5 promoter that may be a useful target for treatment of HIV-1 infection.
IMPACT
These results identify the first site in CCR5 promoter that may be a useful target for treatment of HIV-1 infection.
1996
This early study in the MACS indicated that there was an important association between MHC polymorphism and susceptibility to HIV and AIDS
Nature Medicine
These findings further support the theory about control of antigen processing by HLA genes and have implications for immunopathogenesis of HIV-1 and other infections.
IMPACT
This study had great impact on our understanding of how host immunity fails to control HIV infection and development of AIDS. It has been been cited 1,277 times to date.
1996
HIV infection drives cells of the immune system to an exhausted state making it easier for the virus to spread
AIDS
T-cells from people living with untreated HIV look like cells taken from people who are very old. This was the first study to show that HIV can age cells to the point where they can’t divide or properly fight HIV. This understanding that HIV infection ages T-cells provided a new pathway for researchers to target with new therapies.
IMPACT
The discovery that HIV can eventually escape T cell control by accelerating aging of T cells identified novel pathways to prevent cellular senescence as potential new therapeutic targets.
1996
Delta 32 allele of CCR5 gene critical in HIV–1 transmission and pathogenesis
Nature Medicine
It is important to understand why some people are more susceptible to HIV infection and progression than others. In this study, we found that two copies of certain genetic variant called the delta 32 CCR5 genotype was present in 3.6% of men without HIV, suggesting that this protected them from becoming infected with HIV. This showed that this genetic variant was important for HIV transmission.
IMPACT
This work showed that persons who are homozygous for the delta 32 allele in the CCR5 gene are highly resistant to sexual acquisition of HIV-1 infection.
1994
Selective elevation of HLA-DR+ CD38- CD8+ cells is a marker of subsequent stable HIV disease
JID
Types of white blood cells important in immune function are lymphocytes; there are many different types of lymphocytes. One of these, called CD38, became prominent among men who became HIV-infected within 6-12months. This type of cell, helps the immune systems of persons with HIV fight the virus. In some men, the levels of these cells remained elevated throughout the first year of infection. Having elevated levels of CD38 cells was associated with also having stable CD4 (T helper cell ) levels which are important for good immune function whereas the others did not. Long-term survivors with HIV ( having healthy levels of CD4 cells [ > 800 cells] for 9 years) also had elevated levels of CD38 cells). So, having elevated levels of CD38 cells was a marker of longer term stable HIV disease.
IMPACT
Very numerous citations.
1990
Major histocompatibility complex (MHC) genes (HLA in humans) regulate the immune response to HIV-1
The Lancet
These findings were one of the first to support the theory about control of antigen processing by HLA genes and have profound implications for immunopathogenesis of HIV-1 and other infections.
IMPACT
This pioneering study provided support for host T cell immunity in controlling HIV infection and AIDS.
1989
Cell-to-cell transmission is responsible for spreading HIV-1 within the body
The Journal of Virology
In this study, the authors wanted to know if the HIV virus could infect cells in the body by hijacking neighboring cells in addition to virus alone infecting cells. The authors found that this virus that was attached to cells can indeed infect cells, and they also found that this infection is not stopped by AZT, an antiretroviral therapy. This information helps scientists design different ART compounds that can be used to stop this additional cellular infection type.
IMPACT
This study indicated that additional ART compounds aside from AZT are necessary in controlling HIV replication.
1989
HIV-1 infection in homosexual men at high risk may occur at least 35 months before antibodies to HIV-1 can be detected
New England Journal of Medicine
Infection with the human immunodeficiency virus type 1 (HIV-1), as demonstrated by viral cultures, has been described in some patients before antibodies to HIV–1 can be detected, but the duration and frequency of such latent infections are uncertain. We selected prospectively a cohort of 133 seronegative homosexual men who continued to be involved in high-risk sexual activity, and we cultured 225 samples of their peripheral-blood lymphocytes, using mitogen stimulation to activate the integrated HIV-1 genome.
HIV-1 was isolated in blood samples from 31 of the 133 men (23 percent), 27 of whom have remained seronegative for up to 36 months after the positive culture. The other four men seroconverted 11 to 17 months after the isolation of HIV-1. In three of them, we studied cryopreserved lymphocytes obtained earlier, using the polymerase chain reaction to amplify small amounts of viral DNA, and we demonstrated that HIV-1 provirus had been present 23, 35, and 35 months before seroconversion.
We conclude that HIV-1 infection in homosexual men at high risk may occur at least 35 months before antibodies to HIV-1 can be detected. A prolonged period of latency in such infections may be more common than previously recognized; the degree of infectiousness during such periods is unknown. (N Engl J Med 1989; 320:1458–62.)
IMPACT
n/a
1988
Rare, asymptomatic persons with HIV have negative HIV serologic testing
Disease Markers
People are typically diagnosed with HIV infection using antibody tests called enzyme-linked immunosorbent assay (ELISA) and Western blot. We identified 4 men with HIV who were asymptomatic from the infection. Although initially they tested positive with the antibody tests, they tested negative later in the infection by antibody tests, but the virus was still detected in their blood. It is important to recognize that rare, asymptomatic persons seropositive for HIV-1 may not remain seropositive but remain infected with HIV.
IMPACT
This work demonstrated that PCR-based applications provide a specific and efficient alternative for direct detection of HIV-1 infection.
HIV Outcomes
2010
Liver disease and homicide/suicide/overdose most common causes of death in women with HIV
JAIDS
The importance of non-HIV associated illnesses as causes of death among women with HIV was not apparent when potent antiviral drugs first became available. The WIHS study was among the first to demonstrate how much liver disease and cardiovascular disease were impacting women with HIV. In addition, homicide, suicide and overdoses were identified as frequent causes of death among women with HIV.
IMPACT
The paper was highly cited as the impact of non-HIV morbidity and mortality became clear in the field.
2009
Lower CD4 cell count on HIV medications linked to AIDS and death
HIV Medicine
Background: The health consequences of not achieving higher CD4 cell counts despite receiving effective HAART are uncertain.
IMPACT
This paper has been cited multiple times as evidence of the clinical importance of CD4 achieved after viral suppression and, therefore, the importance of starting ART at higher CD4 cell counts.
2004
GB virus C, a Flaviviridae Pegivirus, has a protective effect in limiting disease progression in PLWH
The New England Journal of Medicine
PLWH and infected with a common virus (GB virus C) have prolonged survival compared to PLWH who are not infected with GB virus C, which could provide important knowledge on how to impede disease progression in PLWH.
IMPACT
Understanding the mechanisms of interaction between GBV virus C and HIV could provide insight into the progression of HIV disease.
1999
In the absence of ART treatment, plasma HIV RNA levels provide prognostic information about the risk of these three specific AIDS-defining illnesses, independently of the CD4 cell count; these data provide a useful reference as researchers investigate changing patterns in the incidence and predictors of opportunistic infections in the era of increasingly active antiretroviral therapies
AIDS
Objectives: To use follow-up on untreated HIV-positive men to assess the prognostic information provided by baseline data on plasma HIV RNA, CD4 cell count, age, and HIV-related symptom status, separately for three specific AIDS-defining illnesses: Pneumocystis carinii pneumonia (PCP), cytomegalovirus (CMV), and Mycobacterium avium complex (MAC).
Included were 734 men with HIV followed 1984-1985 through mid-1988 who did not have ART available : A total of 138 cases of opportunistic infections: pneumocystis pneumonia (PCP), cytomegalovirus (CMV) and mycobacterium avian complex (MAC) occurred . For PCP and CMV, having high HIV viral loads and lower T helper cell counts (CD4) ere associated with increased risk. For MAC, having oral thrush, fever, and high HIV viral load were the primary risk factors. Further analysis highlighted the importance of monitoring viral load levels in addition to CD4 cell counts when evaluating risk of developing PCP.
Conclusions: In the absence of ART , HIV viral load levels provide important information about the risk of these three specific AIDS-defining illnesses, independently of the CD4 cell count.
IMPACT
The independent predictive value of HIV RNA was novel and cited by many.
1998
Plasma viral load and CD4 T lymphocyte counts are significant prognostic markers of HIV-1 infection
Annals of Internal Medicine
Plasma viral load strongly predicts the rate of decrease in CD4 T lymphocyte count and progression to AIDS and death, but the prognosis of HIV-infected persons is more accurately defined by combined measurement of plasma HIV-1 RNA and CD4 T lymphocytes.
IMPACT
This 1997 MACS-wide study, with over 2,800 citations as of April 2024, confirmed and extended the 1996 Pittsburgh MACS study showing the importance of HIV viral load and CD4 T cell count together as prognostic markers in PLWH.
1990
Serum markers that reflect immune activation together with CD4 T cell counts are important factors in evaluating responses to ART
The New England Journal of Medicine
Activation of the immune system with associated increases in serum biomarkers is important to determining disease progression in PLWH,
IMPACT
This MACS study supported the importance of serum inflammatory biomarkers in assessing risk for disease progression in PLWH.
HIV Pathogenesis
2021
The gut microbiome impacts HIV susceptibility
Microbiome
The authors wanted to find out if the microbiome was associated with HIV infection in participants in the MACS. The team studied changes in the microbiome in patient samples from 1984-1985, and they found that specific changes in the microbiome were associated with increased HIV infection. These findings can help inform HIV prevention measures by targeting the microbiome.
IMPACT
This is one of the first studies to investigate the impact of the microbiome on HIV susceptibility.
2019
B cells are a target for cell to cell HIV transmission
Open Forum Infectious Diseases
It was previously known that HIV can infect cells in the body by interacting with other cells that contain the virus. This study looked at a specific type of cell, B cells, and their role in continuing HIV infection. They found that indeed B cells can directly pass the virus to CD4 T cells, and that this infection is not stopped by antiretroviral therapy. Thus, this is a target for improved ART drugs.
IMPACT
This study is one of the first to describe B cell trans infection of CD4 T cells directly.
2009
CCL3L1 gene expression phenotype does not contributes to HIV susceptibility
Nature medicine
People can be more or less susceptible to the effects of HIV infection depending on immune system factors. In this study, we looked at gene called CCL3L1 that can be present in different amounts in people. We found that the amount of CCL3L1 in people with HIV affected how HIV progressed.
IMPACT
The number of copies of the gene encoding C-C chemokine ligand 3-like 1 (CCL3L1)—a ligand for the HIV co-receptor CCR5— does not influence susceptibility to HIV infection and progression to AIDS.
2001
Change in a single amino acid in class I HLA-B*35 genotype accelerates the progression to AIDS
The New England Journal of Medicine
A genetically inherited, single amino acid in PLWH significantly controls their susceptibility to develop AIDS.
IMPACT
A single amino acid change in HLA molecules has a substantial effect on the rate of progression to AIDS. The different consequences of HLA-B*35-PY and HLA-B*35-Px.
HIV Treatment
2023
Integrase Inhibitors are Associated with Neuropsychiatric Symptoms in Women with HIV
Journal of Neuroimmune Pharmacology
Women with HIV (WWH) are more likely to discontinue/change antiretroviral therapy (ART) due to side effects including neuropsychiatric symptoms. Efavirenz and integrase strand transfer inhibitors (INSTIs) are particularly concerning. We focused on these ART agents and neuropsychiatric symptoms in previously developed subgroups of WWH that differed on key sociodemographic factors as well as longitudinal behavioral and clinical profiles. INSTIs, but not efavirenz, were associated with symptoms among key subgroups of WWH. Among those with HIV legacy effects, dolutegravir and elvitegravir were associated with greater stress/anxiety and avoidance symptoms; dolutegravir was also associated with greater re-experiencing symptoms. Elvitegravir related to greater re-experiencing and hyperarousal among women with well-controlled HIV with vascular comorbidities. Raltegravir was associated with less hyperarousal, but only among women aged ≤ 45 years. The adverse neuropsychiatric effects of INSTIs do not appear to be consistent across all WWH.
IMPACT
This article is in a high impact journal. Although it does not have any citations yet (it was just published in 2023), it does have novel information about the impact of legacy medications on mood and mental health.
2019
EFV not associated with cognitive loss or depression
AIDS
Although Efavirenz is associated with side effects involving the central nervous system, it remains largely unknown whether switching off EFV improves neuropsychological performance. We found that discontinuation of EFV is not associated with changes in neuropsychological performance or severity of depression in men. Furthermore, we did not observe differences among participants who were never on EFV, continuously on EFV, and on EFV and then switched off. These findings were reassuring for people who were concerned that efavirenz may worsen their mental health and cognition
IMPACT
There have been 7 citations of this publication. The article also helps to inform clinical providers who may be changing older regimens of PWH.
2015
Immune system activation not eliminated by antiretroviral therapy
AIDS
Most markers of immune activation were relatively normalized in men with HIV suppression, but some were not including C-reactive protein (CRP), interleukin-6, which are associated with aging, frailty, and cardiovascular disease, and several markers of activation of macrophages. This residual immune activation, particularly monocyte/macrophage activation, may represent a target for treatments to improve long-term health outcomes of HIV-infected individuals receiving HAART.
IMPACT
This study has been cited over 400 times and has been influential in focusing research efforts on understanding mechanisms that may contribute to persistent immune activation in people with HIV suppression, which may lead to better treatments to reduce this persistent immune activation that is associated with adverse outcomes in people living with HIV as they age.
2010
ABC use was not associated with plasma elevations in hsCRP, IL-6, and D-dimer; hence, mechanisms other than increased systemic inflammation may account for ABC's reported association with increased cardiovascular disease
AIDS
Objective: To assess associations between abacavir (ABC, an anti-HIV medication) use and inflammation.
IMPACT
Publication has been cited by by many to support the contention that adverse cardiovascular effects associated with abacavir use are not mediated through elevations in systemic inflammation.
2004
CD4+ and viral load treatment response predict HIV prognosis
Annals of Internal Medicine
This study was done to understand whether HIV-related lab markers (such as T cells and HIV viral load) measured before or after starting HIV treatment predict important clinical outcomes, including developing AIDS or death. Levels of T calls and viral load measured after starting HIV treatment predicted new AIDS-defining illness or death, but pretreatment levels of these markers did not. These findings show that patients with a good response to HIV treatment have a favorable prognosis even if they had poor T cell and HIV viral load levels before starting treatment.
IMPACT
This study provided data that influenced HIV treatment guidelines and was cited in the 2013 and 2015 CDC treatment guidelines.
2002
HAART can be deferred until CD4+ count is between 350 and 200/µL
Archives of Internal Medicine
This study was done to understand the best timing to start antiretroviral therapy in terms of stage of HIV disease (measured by CD4+ T cells and HIV viral load), in order to help guide clinical decision making. Women with CD4+ T cells below 200 or HIV viral load greater than 50, 000 before starting antiretroviral therapy had a higher risk of developing AIDS and death. These findings suggested that it was safe to wait to start antiretroviral therapy until the CD4+ cell count is between 350 and 200/µL, in order to balance the toxicity of available HIV treatments at the time.
IMPACT
This study provided key data guiding clinical decision-making on the timing of ART initiation.
2002
This analysis supports recommendations to defer therapy in HIV-1 infected individuals with CD4 cell counts > 350 x 10(6)/l and HIV RNA < 60 000 copies/ml and in persons with CD4 cell counts between 201 x 10(6) and 350 x 10(6)/l and 350 x 10(6) CD4 cells/l and 29% with CD4 cell counts between 201 x 10(6) and 350 x 10(6)/l may, with close monitoring, safely defer therapy.
AIDS
Objective: To determining how long highly ART initiation can be delayed in PWH.
IMPACT
Multiple sources at the time and guidelines bodies cited these data to inform guidelines regarding timing of initiation of ART.
2001
Stronger response to antiretroviral therapy in persons with no compared to prior treatment experience
LWW
When highly active treatments for HIV became available in 1995, it was important to understand how people were responding to these treatments. The authors found that after starting treatment for HIV infection, men who had never received antiretroviral drugs had better increases in CD4 lymphocyte count and were more likely to have undetectable viral loads than men who had prior HIV treatments. Additionally, the study found that men who carried a mutation gene called CCR5 had higher CD4 T cell counts.
IMPACT
A study on the effects of highly active antiretroviral therapy on HIV RNA and CD4 cell count found that those MACS patients who had not previously undergone any treatment had the best response, with the baseline CD4 cell count identified as a predictor of response; age had little effect on early CD4 cell recovery after starting treatment.
Kidney Function
2018
Kidney function decline over time among men with with HIV was associated with HAART use but no individual antiretroviral drug, traditional kidney disease risks; proteinuria was nearly seven times more common in ART-treated men than HIV-uninfected men and it reflected recent eGFR decline and predicted subsequent eGFR decline
AIDS
Among 917 HIV+ men MACS men on HAART, 159 HIV+ men men not on HAART, and 1305 HIV negative MACS men seen from October 2003 to September 2014, factors significantly associated with declines in kidney function over time were: 1) receiving HAART but not any specific antiviral drug), age greater than 50, high blood pressure, diabetes, current smoking. Protein in urine existed in 14.9% of visit-pairs among men on HAART , 5.8% among men with HIV not on HAART, , and 1.9% men without HIV, and was associated with greater risk of kidney function decline in the following years. Having protein in urine was associated with HAART use (compared to HIV negative men), being at least 50 years (vs. <40), diabetes, high blood pressure, t smoking, hepatitis C virus-infection and, among HIV+ men, lower CD4 cell count, Among men on HAART with protein in urine, having a detectable HIV viral load, having used certain antivirals (tenofovir, FTC, ritonavir, atazanavir, any protease inhibitor, or fluconazole) was associated with more than 3% annual eGFR decline.
IN conclusion, Kidney function decline over time was associated with HAART use (but no individual antiretroviral drug, and traditional risk factors for kidney disease risks. Having protein in urine was nearly seven times more common in HAART-treated men than HIV uninfected men, was more common in men with recent decline in kidney function declines, and predicted kidney function decline.
IMPACT
Unknown
2017
Greater coronary artery calcium burden is apparent among individuals with early kidney disease, regardless of HIV serostatus; increased urine protein: creatinine is associated with a greater extent of CAC, particularly among persons without HIV
Coronary Artery Disease
Decreased kidney function and greater urine protein are associated with increased coronary artery calcium (CAC)- blockage the arteries supplying the heart. We investigated whether the associations between kidney function and the amount of protein in urine differ among persons with and without HIV
Using data from the Multicenter AIDS Cohort Study (MACS), a US study of men who have sex with men, we analyzed data from men with and without HIV who had CT scans of heart that measure measure CAC. Statistical analysis evaluated whether or not associations between relationships between kidney function, urine protein, and amount of CAC differed between persons with and without HIV
Results: Lower kidney function was associated with more CAC and this relationship was similar among persons with and without HIV. Greater amounts of urine protein were associated with greater CAC, and this relationship was greater for persons without HIV.
Conclusion: Greater CAC existed among persons with early kidney disease, regardless of HIV serostatus. Increased urine protein was associated with a greater extent of CAC especially among HIV persons without HIV .
IMPACT
Unknown
2014
Iohexol-based GFR (iGFR) was higher than eGFR in this population of HIV-infected and -uninfected men who have sex with men; presence of chronic kidney disease (CKD) was predicted equally well by iGFR and eGFR, but associations of chronic HCV infection and history of clinically-defined AIDS with mildly decreased GFR were seen only with iGFR
PLoS One
Objective: Formulas used to estimate glomerular filtration (GFR, kidney function) have not been well studied in persons with HIV.; we evaluated the relationships between having HIV infection and other known l risk factors for kidney disease by directly measuring kidney function
Design: Measurement of iohexol-based GFR (iGFR) in men with HIV( HIV+) men (n = 455) taking antiretroviral therapy, and men without HIV (HIV(-)) men (n = 258) in the Multicenter AIDS Cohort Study. Iohexol is a substance injected into a vein in the arm; measuring levels of iohexol in the blood during the hours after injecting it provides a direct measure of kidney function since the body eliminates iohexol through the kidneys. This iGFR was compared the standard way of estimating kidney function by measuring a substance in the blood called creatinine, which the body produces, and using a formula, eGFR.
Results: Median iGFR was higher among HIV(+) than HIV(-) menand was higher than median eGFR. Mean iGFR was lower in men who were older, had chronic hepatitis C virus (HCV) infection, or had a history of AIDS. Low iGFR was associated with these factors and with black race. Other than age, factors associated with low iGFR were not observed with low eGFR. Chronic kidney disease was more common in HIV(+) than HIV(-) men; predictors of CKD were similar using iGFR and eGFR.
Conclusions: iGFR was higher than eGFR in this group HIV-infected and -uninfected men who have sex with men. CKD was predicted equally well by iGFR and eGFR, but associations of chronic HCV infection and having a history of clinically-defined AIDS with mildly decreased GFR were seen only with iGFR.
IMPACT
Unknown
Liver
2016
Hepatitis E virus causes acute and chronic infections in people living with HIV
Hepatology
The impact of hepatitis E virus on people living with HIV in the United States is unknown. We tested women and men living with HIV and found 2 women with acute hepatitis E and 1 woman with chronic hepatitis E that lasted for 4 years. People living with HIV in the United States can get hepatitis E but infections are rare.
IMPACT
Screening people living with HIV for hepatitis E virus (e.g., with antibody tests or by PCR) is not recommended in the United States, in part because of the data from this paper.
2010
Human leukocyte antigen (HLA) genes affect whether people living with HIV get chronic hepatitis C if they are exposed to the virus
Hepatology
The impact of human leukocyte antigen (HLA) genes on hepatitis C disease outcomes is not well understood. We found that two kinds of HLA - class I and class II - affected whether women got chronic hepatitis C. HLA genes affect hepatitis C disease outcomes in people living with HIV.
IMPACT
This study established HLA genotype is an important predictor of hepatitis C pathogenesis in people living with and without HIV. These findings were confirmed in subsequent candidate gene and genome-wide association studies.
Mental Health and Stigma
2023
Specific antiretrovirals linked to depressive symptoms in women with HIV
Common antiretroviral combinations are associated with somatic depressive symptoms in women with HIV
AIDS
We examined the association between common ART regimens and depressive symptoms in women with HIV (WWH). Specific ART combinations are associated with depressive symptoms related to how the body fees (i.e., tired, achy) in WWH with chronic depression.
IMPACT
This a new article so it has not been referenced yet. But it is in a top journal and we believe the findings are novel.
2023
Abuse, mental health, substance use disorders predict health outcomes in women with HIV
Psychosomatic Medicine
We examined patterns of trauma, mental health disorders (MHD), substance use disorder (SUD), and associations with later cognitive and health outcomes. Six distinct profiles emerged: 1) no/negligible sexual/physical trauma, MHD, or SUD (39%); 2) preadolescent/adolescent sexual trauma with anxiety and SUD (22%); 3) SUD only (16%); 4) MHD + SUD only (12%); 5) early childhood sexual/physical trauma only (6%); and 6) early childhood sexual/physical trauma with later MHD + SUD (4%). Profiles including early childhood trauma had the largest number of midlife conditions (i.e., cognitive, cardiovascular, HIV-related). Preadolescent/adolescent sexual trauma with anxiety and SUD predicted both global and domain-specific cognitive declines.
IMPACT
This article is in a high impact journal. Although it has not been cited yet, we believe that given the novelty of the information, it will become a seminal work highlighting the various profiles of mental health, sexual abuse, and substance abuse in women.
2022
Intersectional stigma is associated with biopsychosocial outcomes across the lifecourse among gay/bi men
American journal of public health
Stigma is a major barrier for gay/bi men in the U.S. We found that experiencing stigma for multiple reasons, such as being Black and gay, was associated with higher risk for several outcomes, including depression, healthcare avoidance, and higher cholesterol.
IMPACT
Helps provide a strong basis for the continued development, refinement, and deployment of anti-stigma interventions, a key priority for NIMH/OAR.
2018
Diverse women with HIV experience intersectional stigma
Social Science & Medicine
Women with HIV in the United States may experience different types of negative social judgment (stigma) that can compromise their mental and physical health. We found that many women living with HIV in different settings across the country felt they were negatively treated by others due to their different identities; including their HIV status, their race, being a woman, and their financial situation, as well as incarceration history and weight. These findings highlight the need for public health strategies to address different stigmas that women with HIV face to promote wellbeing and reduce health disparities.
IMPACT
This study has been cited over 150 times and has been used to inform the development of intersectional stigma-reduction interventions to support diverse women with HIV.
2014
Higher risk of health disparities among bisexual men compared with gay men
Journal of acquired immune deficiency syndromes
Bisexual men may have higher risks for negative mental health, substance use, and HIV-related outcomes compared with gay men. We found that, over a 6-year span, that bi men face higher risk of depression and substance use than gay men. We also found among those who are living with HIV, that bi men have a higher risk of detectable viral load compared with gay men.
IMPACT
Helped to inspire a field of research analyzing bisexual health disparities in the context of HIV; influenced the development of the first NIH Bisexual Health Research Working Group.
Pulmonary and Sleep
2023
Men with HIV more likely to have sleep-disordered breathing
Chest
Sleep-disordered breathing (SDB) is associated with many adverse health effects, including daytime sleepiness and impaired quality of life, but how HIV affects breathing in sleep was not well understood. Using state-of-the-art technology for assessing breathing during overnight sleep at home, we found that prevalence of SDB was high overall but that mild and moderate SDB was more common in men with than without HIV, independent of HIV viral load, CD4 cell count, and use of antiretroviral medications. The data emphasize the importance of diagnosing SDB in people with HIV.
IMPACT
This study is the first of its kind, was published in a leading journal dealing with sleep, and is likely to stimulate research acquiring objective sleep data in people with HIV infection.
2022
HIV linked to more lung symptoms
J AIDS
Asthma, a chronic lung condition characterized by wheezing and shortness of breath, is common among PLWH. HIV infection does not appear to increase occurrence of asthma, but PLWH (especially men) have more breathing symptoms.
IMPACT
This is the first comprehensive description of asthma among PLWH.
Sex Hormones and Bone Health
2022
HIV infection and menopausal stage are independent predictors of lower bone mineral density (BMD)
Clinical Infectious Diseases
Women with HIV are at high risk of bone loss and fractures (broken bones) and may lose bone even faster as they transition through menopause. In this study, we found that both HIV infection and menopausal stage were independent predictors of lower bone mineral density (BMD) and together HIV and menopause had even greater effect on spine and hip BMD. These findings highlight the need to develop strategies to reduce the risk of osteoporosis (weak bones) and fracture risk in the growing population of women aging with HIV.
IMPACT
This study demonstrates the independent and combined impact of HIV and menopause on bone loss as women with HIV age.
2019
Frailty is a risk factor for fractures in women with HIV
AIDS
This study examined the relationship between frailty (and different individual aspects of being frail) and the development of fractures (broken bones) among middle-aged women with and without HIV. We found that frailty was a strong predictor of fractures in women with and without HIV, and that for women with HIV who had one fracture, frailty predicted having a second fracture. Our findings suggest that as women with HIV continue to age, early screening for frailty might help identify women at high risk of fracture.
IMPACT
Early screening for frailty might help identify women at high risk of fracture as they age with HIV.
2018
Testosterone use very high in older men with HIV
HIV Medicine
It's not clear if testosterone replacement in the long term is good or bad for health in older men. We found that testosterone use was very high in the men with HIV in the MACS and was over 3 fold higher than in men without HIV. We also found that men with HIV were less likely to stop testosterone after a warning was given by the US Food and Drug Administration about potential heart problems. These findings suggest that testosterone use among men with HIV should be carefully monitored.
IMPACT
This study was cited in the Primary Care Guidelines of the HIV Medicine Association of the Infectious Disease Society of America.
Social Determinants of Health/Health Disparities
2022
An expanded concept of vocational rehabilitation may improve employment in women with HIV
Journal of the Association of Nurses in AIDS Care
Women living with HIV have lower employment rates and more difficulty finding and keeping jobs than their counterparts without HIV. Although past concerns surrounding employment have centered on HIV-clinical outcomes and management of HIV, not enough work has examined the holistic context associated with employment among this underemployed population. We found that there was a reciprocal relationship between employment acquisition and occupational productivity, and psychological health, physical health, social support, and empowerment. These findings support an extended conceptualization of vocational rehabilitation to improve employment outcomes, and the use of peer support groups to increase social capital, empowerment, knowledge, and resources among women living with HIV. NIOSH featured these findings in their annual EOP report.
IMPACT
Dr. Wise's work was highlighted in NIOSH's Annual EOP Report. Her work has influenced directions for future research and has laid the groundwork for future interventions and policy in several ways. Namely, this work has:1) Elucidated the relationships between improved health outcomes and employment among women living with HIV (WLHIV) and provided the pilot data critically needed to underscore the call for occupational programs among WLHIV; 2) highlighted the need for a more holistic approach to vocational rehabilitation and screening needs among WLWH; and 3) important inferences for total worker health and return‐to‐work policies among other populations. Notably, behaviors associated with improved psychological health, problem solving strategies, and personal empowerment can be taught through interventions, thus improving employment and health outcomes across populations. This work may be useful in the advocacy of expanding the provision of vocational rehabilitation within the Ryan White CARE Act and Ryan White program.
2018
For Women With HIV, Unstable Housing Is Linked to Poorer Health Outcomes
Social Science & Medicine, Impact Factor 5.4
Unstable housing, including homelessness, is a public policy concern for all populations, and more critically for people with a serious health condition such as HIV infection. We measured the effect of unstable housing on HIV treatment biomarkers, such as viral suppression and adequate CD4+ T-cell count. We used data (1995–2015) from 3082 participants of the Women's Interagency HIV Study (WIHS) sites in Bronx and Brooklyn (NY), Chicago (IL), Los Angeles and San Francisco (CA), and Washington (DC). We found that unstable housing reduces the likelihood of viral suppression, and decreases the probability of having an adequate CD4 cell count. Increasing efforts to improve housing assistance, including HOPWA, and other interventions to make housing more affordable for low-income populations, and people living with HIV in particular, may be warranted not only for the benefits of stable housing, but also to improve HIV-related outcomes.
IMPACT
Publication was highlighted in a National Affairs Blog and POZ magazine.
2017
Social support predicts viral load suppression in gay and bisexual men living with HIV
AIDS Care
People with HIV often have difficulty maintaining an undetectable viral load. We found that gay/bi men with HIV who had high levels of social support were more likely to have undetectable viral loads than those reporting lower levels of social support. Social support was particularly impactful for gay/bi men with other risk factors for unsuppressed viral load such as depression and substance use.
IMPACT
This study helped to provide foundational frameworks for resiliency-based research and practice initiatives that are ongoing for sexual minority men living with HIV in the U.S., Canada, and Europe.
2016
Smoking strongly linked to atherosclerosis in men with HIV
PLoS One
Background: We looked for links between smoking, alcohol use, and recreational drug use and coronary artery plaque (narrowing or blockage of the blood vessels that supply the heart) among men with and without HIV in the Multicenter AIDS Cohort Study (MACS).
Methods: Among 1005 MACS participants (, 621 HIV+ and 384 HIV-) underwent n CT scanning to measure coronary artery calcium (hard deposits in the heart blood vessels) ; 764 underwent coronary CT angiograms (IV contrast dye injected into a vein to allow a scan of heart arteries to assess for blockage). MACS particpants self-reported any use of alcohol, tobacco, smoked/inhaled cocaine, methamphetamine, ecstasy, marijuana, inhaled nitrites, and erectile dysfunction drugs (like Viagra or Cialis) at semi-annual visits beginning 10 years prior to CT scanning.
Results: Among HIV+ men, current smoking, former smoking, and cumulative pack years of smoking were associated with multiple coronary plaque measures (coronary artery calcium presence and amount, total coronary plaque presence and amount, calcified (hard) plaque presence, and stenosis (blockage of a coronary artery >50%). Smoking was associated with fewer plaque measures among HIV- men; current smoking and calcified plaque amount was the only such association. Heavy alcohol use (>14 drinks/week) was associated with coronary artery stenosis among HIV+ men. Among HIV- men, low/moderate (1-14 drinks/week) and heavy alcohol use were associated with having less coronary artery calcium and calcified plaque amount. Use of other recreational drugs were less likely to be associated hated with coronary plaque.
Conclusion: Smoking is strongly associated with coronary plaque among HIV+ men, underscoring the value of smoking cessation for HIV+ persons. Alcohol use may protect against coronary artery calcium (hard plaque) and its worsening in HIV- (but not HIV+) men. Use of other recreational drugs were less likely to be associated hated with coronary plaque.
IMPACT
Unclear
2015
The psychosocial syndemic of depression, substance use, and risky sexual behavior predicts ART adherence and viral load patterns among gay/bi men with HIV
Effects of syndemics on HIV viral load and medication adherence in the multicentre AIDS cohort study
AIDS
Gay/bi men living with HIV often experience mental and behavioral health issues such as depression and substance use. We found that men with higher levels of these intertwined health issues were more likely to report lower adherence to HIV medications and had higher odds of detectable viral load than gay/bi men with lower levels of these health issues.
IMPACT
Helped initiate corroborating research that contributed to wraparound care initiatives and substantive NIH funding opportunities related to syndemics and HIV care.
2014
Age-Related Diseases Are Bigger Problem for African American Women
AIDS Patient Care and STDs
Overall, this study demonstrates that HIV and co-morbidity self-management are inextricably linked. We can no longer afford to view engagement in HIV care as a single-disease issue and hope to attain optimal health and well-being in our HIV affected populations. Optimal HIV self-management must be framed within a larger context that simultaneously addresses HIV and co-morbidities, while considering how social and cultural factors uniquely intersect to influence older African American women’s self-management strategies.
IMPACT
The Journal AIDS Patient Care and STDs issued a press release highlighting the importance of this paper that it established the importance of co-morbidities for African American women aging with HIV. For them, "self-managing their HIV as they age is proving to be less of a challenge than dealing with age-related diseases such as diabetes or hypertension and socioeconomic and emotional aspects of aging." This is one of the first papers to establish the importance of co-morbidities in managing HIV. This paper is based on qualitative data, providing voice to HIV+ women's opinions.
2004
Predictors of not using HAART among women with HIV
American Journal of Public Health
In the early 2000's, one in 4 WIHS women who could have benefited from potent HIV therapy were not on it. We found that women who were not prescribed or not taking potent therapy were more likely to be non-white, have a history of abuse and/or having a history of using crack, cocaine or heroin. This study was one of the first to highlight these inequities in use of ART and the challenges women with HIV faced.
IMPACT
This publication was cited frequently as it was one of the first to document the relationship between history of abuse and non-use of potent ARV.
MWCCS in the News
Blindspot: Stories from the early days of AIDS-and the people who refused to stay out of...
WNYC Studios
Hosted by Kai Wright with Lizzy Ratner
What can 35-year-old stool samples tell scientists about HIV/AIDS?
Science Daily (12/08/21)
Science Daily editors
Our 25 Amazing People of the Year – Who Are Also Living with HIV
HIVplusmag.com (Nov./Dec. 2021)
PLUS editors
How activists pushed to include people with HIV in COVID-19 vaccine trials
GMA (2/15/2021)
Dr. Divya Chhabra; Video by Will Linendoll & Tony Morrison
‘Déjà vu’: HIV-positive Pittsburghers say we have much to learn about COVID by comparing it to...
PublicSource (2/2/2021)
Oliver Morrison
SELECT PUBLICATIONS
Psychosocial aspects of AIDS risk
Psychopharmacol Bull 1986
Ostrow, D.G., Joseph, J., Monjan, A., Kessler, R., Emmons, C., Phair, J., Fox, R., Kingsley, L., Dudley, J., Chmiel, J.S. and Van Raden, M.
The Women’s Interagency HIV Study. WIHS Collaborative Study Group
Epidemiology 1998
Barkan, S. E., Melnick, S. L., Preston-Martin, S., Weber, K., Kalish, L. A., Miotti, P., Young, M., Greenblatt, R., Sacks, H., Feldman, J. and Grp, WIHS Collaborative Study
Characteristics Of The MACS-WIHS Combined Cohort Study: Opportunities For Research On Aging With Hiv In The...
Am J Epidemiol, 2021
Gypsyamber D'Souza, Fiona Bhondoekhan, Lorie Benning, Joseph B Margolick, Adebola A Adedimeji, Adaora A Adimora, Maria L Alcaide, Mardge H Cohen, Roger Detels, M Reuel Friedman, Susan Holman, Deborah J Konkle-Parker, Daniel Merenstein, Igho Ofotokun, Frank Palella, Sean Altekruse, Todd T Brown, Phyllis C Tien
The Changing Science of HIV Epidemiology in the United States
Am J Epidemiol 2019
Gypsyamber D'Souza, Elizabeth T Golub, Stephen J Gange
The Women’s Interagency HIV Study: an Observational Cohort Brings Clinical Sciences to the Bench
Clin Diagn Lab Immunol 2005
Bacon, M. C., von Wyl, V., Alden, C., Sharp, G., Robison, E., Hessol, N., Gange, S., Barranday, Y., Holman, S., Weber, K. and Young, M. A.
Short-term binge drinking, marijuana, and recreational drug use trajectories in a prospective cohort of people living...
Drug Alcohol Depend, 2022
Steven Meanley, Seul Ki Choi, Azure B Thompson, Jacquelyn L Meyers, Gypsyamber D'Souza, Adaora A Adimora, Matthew J Mimiaga, Mirjam-Colette Kempf, Deborah Konkle-Parker, Mardge H Cohen, Linda A Teplin, Lynn Murchison, Leah H Rubin, Anna A Rubtsova, Deborah Jones Weiss, Brad Aouizerat, Mackey R Friedman, Michael W Plankey, Tracey E Wilson
Exploring the Anal Microbiome in HIV positive and high risk HIV negative Women
AIDS Res Hum Retroviruses, 2022
Jessica Wells, Jinbing Bai, Despina Tsementzi, Camber Ileen Jhaney, Antonina Foster, Deborah Watkins Bruner, Theresa Gillespie, Yunxiao Li, Yi-Juan Hu
The Association Between HIV Status, Estradiol, and Sex Hormone Binding Globulin Among Premenopausal Women in the...
J Womens Health (Larchmt), 2022
Sally B Coburn, Jodie Dionne-Odom, Maria L Alcaide, Caitlin A Moran, Lisa Rahangdale, Elizabeth T Golub, Leslie Stewart Massad, Dominika Seidman, Katherine G Michel, Howard Minkoff, Kerry Murphy, Todd T Brown, Kala Visvanathan, Bryan Lau, Keri N Althoff
Perceptions of Anal Cancer Risk Among HIV-Positive and High-Risk HIV-Negative Women
J Low Genit Tract Dis, 2022
Jessica Wells, Rasheeta Chandler, Lisa Flowers, Sudeshna Paul, Anjali Sharma, Nia Kalifa, Marcia Holstad
Association of poor sleep with depressive and anxiety symptoms by HIV disease status: Women’s Interagency HIV...
J Acquir Immune Defic Syndr, 2021
Elizabeth Daubert, Audrey L French, Helen J Burgess, Anjali Sharma, Deborah Gustafson, Sushma K Cribbs, Deborah Jones Weiss, Catalina Ramirez, Deborah Konkle-Parker, Seble Kassaye, Kathleen M Weber
Positive Psychological Factors and Life Themes in Relation to Health Outcomes in Women Living with HIV
Int J Behav Med, 2021
Leslie R Brody, Yudelki Firpo-Perretti, Dana Bruck-Segal, Sannisha K Dale, Elizabeth G Ruffing, Clair Cassiello-Robbins, Kathleen M Weber, Mardge H Cohen
Cardiovascular risk score associations with frailty in men and women with or at risk for HIV
AIDS, 2021
Kuniholm, Mark H.; Vásquez, Elizabeth; Appleton, Allison A.; Kingsley, Lawrence; Palella, Frank J.; Budoff, Matthew; Michos, Erin D.; Fox, Erving; Jones, Deborah; Adimora, Adaora A.; Ofotokun, Igho; D'souza, Gypsyamber; Weber, Kathleen M.; Tien, Phyllis C.; Plankey, Michaelm; Sharma, Anjalin; Gustafson, Deborah R.
Long-Acting Injectable ART and PrEP Among Women in Six Cities Across the United States: A Qualitative...
AIDS Behav, 2021
Morgan M Philbin, Sadie Bergen, Carrigan Parish, Deanna Kerrigan, Elizabeth N Kinnard, Sarah Reed, Mardge H Cohen, Oluwakemi Sosanya, Anandi N Sheth, Adaora A Adimora, Jennifer Cocohoba, Lakshmi Goparaju, Elizabeth T Golub, Michael Vaughn, José I Gutierrez Jr, Margaret A Fischl, Maria Alcaide, Lisa R Metsch
Long-Acting Injectable ART and PrEP Among Women in Six Cities Across the United States: A Qualitative...
AIDS Behav, 2021
Morgan M Philbin, Sadie Bergen, Carrigan Parish, Deanna Kerrigan, Elizabeth N Kinnard, Sarah Reed, Mardge H Cohen, Oluwakemi Sosanya, Anandi N Sheth, Adaora A Adimora, Jennifer Cocohoba, Lakshmi Goparaju, Elizabeth T Golub, Michael Vaughn, José I Gutierrez Jr, Margaret A Fischl, Maria Alcaide, Lisa R Metsch
Patient Health Literacy and Communication with Providers Among Women Living with HIV: A Mixed Methods Study
AIDS Behav, 2021
Henna Budhwani, C Ann Gakumo, Ibrahim Yigit, Whitney S Rice, Faith E Fletcher, Samantha Whitfield, Shericia Ross, Deborah J Konkle-Parker, Mardge H Cohen, Gina M Wingood, Lisa R Metsch, Adaora A Adimora, Tonya N Taylor, Tracey E Wilson, Sheri D Weiser, Oluwakemi Sosanya, Lakshmi Goparaju, Stephen Gange, Mirjam-Colette Kemp, Bulent Turan, Janet M Turan