Our objective was to describe the association that childcare burden, household composition, and health care utilization have with adherence to highly active antiretroviral therapy (HAART) among women in the United States. The primary outcome was 95% or more adherence to HAART evaluated at 10,916 semiannual visits between October 1998 and March 2006 among 1419 HIV-infected participants enrolled in the Women’s Interagency HIV Study. HAART adherence levels of 95% or more were reported at 76% of the semiannual visits. At only 4% of the person-visits did women report either quite a bit or extreme difficulty in caring for child; at 52% of the person-visits women reported at least one child 18 years of age or older living in the household. We found a one-unit increase in the difficulty in caring for children (childcare burden was assessed on a 5-point scale: not difficult [1] to extremely difficult [5]) was associated with a 6% decreased odds of 95% or more HAART adherence (adjusted odds ratio [OR]=0.94; p=0.07). Each additional child 18 years of age or less living in the household was associated with an 8% decreased odds of 95% or more adherence (adjusted OR=0.92, p=0.03). Both the number and type of adult living in the household, as well as health care utilization were not associated with HAART adherence. Greater child care burden and number of children 18 years old or younger living in household were both inversely associated with HAART adherence. Assessing patients’ difficulties in caring for children and household composition are important factors to consider when addressing adherence to HAART.

doi:10.1089/apc.2008.0161

PMCID: PMC2674283 PMID: 19243274

2. Association between human immunodeficiency virus (HIV) infection and stiffness of the common carotid artery

Stroke; a journal of cerebral circulation 2010;41(10):2163-2170.

Background and purpose

Human immunodeficiency virus (HIV)-infected persons taking highly active antiretroviral therapy (HAART) may have an increased risk for cardiovascular-related events, although the underlying mechanism remains unclear. We tested the hypothesis that carotid arterial stiffness was higher among persons taking HAART compared to HAART-naïve and HIV-uninfected persons.

Methods

Between 2004 and 2006, we performed high resolution B-mode ultrasound on 2,789 HIV-infected and HIV-uninfected participants of the Women’s Interagency HIV Study (WIHS; 1865 women) and the Multicenter AIDS Cohort Study (MACS; 924 men) and determined carotid arterial distensibility, a direct measure of carotid arterial stiffness. We used generalized estimating equations to evaluate the association between distensibility and HIV infection, CD4+ cell count, and exposure to HAART adjusted for demographic, behavioral, and clinical characteristics.

Results

In multivariable analysis, distensibility was 4.3% lower (95% confidence interval (CI): -7.4% to -1.1%) among HIV-infected versus uninfected participants. Among HIV-infected participants with fewer than 200 CD4+ cells, distensibility was 10.5% lower (95% CI: -14.5% to -6.2%) than that among HIV-uninfected participants, and this effect did not differ significantly by cohort or race. Concurrent HAART use was independently associated with lower distensibility among MACS participants but not among WIHS participants.

Conclusions

Our finding that advanced HIV-related immunosuppression was associated with increased carotid arterial stiffness independent from the effects of traditional atherosclerosis risk factors suggests that the etiologic mechanism underlying reports of an increased cardiovascular disease risk among HIV-infected individuals might involve HIV-related immunosuppression leading to vascular dysfunction and arterial stiffening.

doi:10.1161/STROKEAHA.110.583856

PMCID: PMC2972735 PMID: 20798374

atherosclerosis; cardiovascular disease; carotid arteries; HIV; epidemiology

3. Association of Child Care Burden and Household Composition with Adherence to Highly Active Antiretroviral Therapy in the Women's Interagency HIV Study

AIDS Patient Care and STDs 2009;23(4):289-296.

Abstract

Our objective was to describe the association that childcare burden, household composition, and health care utilization have with adherence to highly active antiretroviral therapy (HAART) among women in the United States. The primary outcome was 95% or more adherence to HAART evaluated at 10,916 semiannual visits between October 1998 and March 2006 among 1419 HIV-infected participants enrolled in the Women's Interagency HIV Study. HAART adherence levels of 95% or more were reported at 76% of the semiannual visits. At only 4% of the person-visits did women report either quite a bit or extreme difficulty in caring for child; at 52% of the person-visits women reported at least one child 18 years of age or older living in the household. We found a one-unit increase in the difficulty in caring for children (childcare burden was assessed on a 5-point scale: not difficult [1] to extremely difficult [5]) was associated with a 6% decreased odds of 95% or more HAART adherence (adjusted odds ratio [OR] = 0.94; p = 0.07). Each additional child 18 years of age or less living in the household was associated with an 8% decreased odds of 95% or more adherence (adjusted OR = 0.92, p = 0.03). Both the number and type of adult living in the household, as well as health care utilization were not associated with HAART adherence. Greater child care burden and number of children 18 years old or younger living in household were both inversely associated with HAART adherence. Assessing patients' difficulties in caring for children and household composition are important factors to consider when addressing adherence to HAART.

doi:10.1089/apc.2008.0161

PMCID: PMC2674283 PMID: 19243274

4. Hormonal Contraception and Metabolic Outcomes in Women with or at Risk for HIV Infection

Journal of acquired immune deficiency syndromes (1999) 2009;52(5):581-587.

Introduction

The use of hormonal contraception (HC) is increasing in HIV-infected women. Both HC and HIV infection have been associated with adverse metabolic outcomes. We investigated the association of progestin-only and combined (estrogen/progestin) HC with disorders of glucose and lipid metabolism in HIV-infected and uninfected women.

Methods

Linear mixed models evaluated the association of HC type with fasting HDL, LDL, triglycerides, the homeostasis model assessment estimate of insulin resistance (HOMA-IR), and glucose in 885 HIV-infected and 408 HIV-uninfected women from the Women's Interagency HIV Study seen between October 2000 and September 2005.

Results

Compared to non-HC users, progestin-only HC was independently associated with lower HDL (-3mg/dL;95% confidence interval[CI]:-5,-1 in HIV-infected and -6mg/dL;95% CI:-9,-3 in HIV-uninfected women), greater HOMA (+0.86;95% CI:0.51,1.22 and +0.56;95% CI:0.12,1.01). Combined HC was associated with higher HDL(+5mg/dL;95% CI:2,7 and +5mg/dL;95% CI:3,7).

Conclusion

Progestin–only HC is associated with lower HDL and greater HOMA-IR than non-HC users. Combined HC may be preferred in HIV-infected women of reproductive age at risk for cardiovascular disease, but interactions with antiretroviral therapy that may impair contraceptive efficacy have been reported. Alternative HC methods that minimize adverse outcomes but maintain efficacy require further study.

PMCID: PMC2886798 PMID: 19950431

HIV/AIDS; hormonal contraception; Depo Provera®; HDL; triglycerides

5. Disclosure of Complementary and Alternative Medicine Use to Health Care Providers among HIV-Infected Women

AIDS patient care and STDs 2009;23(11):965-971.

To determine prevalence and predictors of complementary and alternative medicine (CAM) use disclosure to health care providers and whether CAM use disclosure is associated with highly active antiretroviral therapy (HAART) adherence among HIV-infected women, we analyzed longitudinal data collected between October 1994 and March 2002 from HIV-infected CAM-using women enrolled in the Women’s Interagency HIV Study. Repeated measures Poisson regression models were constructed to evaluate associations of selected predictors with CAM use disclosure and association between CAM use disclosure and HAART adherence. A total of 1377 HIV-infected women reported CAM use during study follow-up and contributed a total of 4689 CAM-using person visits. The overall prevalence of CAM use disclosure to health care providers was 36% across study visits. Women over 45 years old, with a college education, or with health insurance coverage were more likely to disclose their CAM use to health care providers, whereas women identified as non-Hispanic Black or other ethnicities were less likely to communicate their CAM usage. More health care provider visits, more CAM domains used, and higher health care satisfaction scores had significant relationships with increased levels of CAM use disclosure. Restricting analysis to use of herbal or nonherbal medications only, similar results were obtained. Compared to other CAM domains, mind–body practice had the lowest prevalence of CAM use disclosure. Additionally, CAM use disclosure was significantly associated with higher HAART adherence. From this study, we showed that a high percentage of HIV-infected women did not discuss their CAM use with health care providers. Interventions targeted towards both physicians and patients may enhance communication of CAM use, avoid potential adverse events and drug interactions, and enhance HAART adherence.

doi:10.1089/apc.2009.0134

PMCID: PMC2801553 PMID: 19821723

6. Disclosure of Complementary and Alternative Medicine Use to Health Care Providers among HIV-Infected Women

AIDS Patient Care and STDs 2009;23(11):965-971.

Abstract

To determine prevalence and predictors of complementary and alternative medicine (CAM) use disclosure to health care providers and whether CAM use disclosure is associated with highly active antiretroviral therapy (HAART) adherence among HIV-infected women, we analyzed longitudinal data collected between October 1994 and March 2002 from HIV-infected CAM-using women enrolled in the Women's Interagency HIV Study. Repeated measures Poisson regression models were constructed to evaluate associations of selected predictors with CAM use disclosure and association between CAM use disclosure and HAART adherence. A total of 1377 HIV-infected women reported CAM use during study follow-up and contributed a total of 4689 CAM-using person visits. The overall prevalence of CAM use disclosure to health care providers was 36% across study visits. Women over 45 years old, with a college education, or with health insurance coverage were more likely to disclose their CAM use to health care providers, whereas women identified as non-Hispanic Black or other ethnicities were less likely to communicate their CAM usage. More health care provider visits, more CAM domains used, and higher health care satisfaction scores had significant relationships with increased levels of CAM use disclosure. Restricting analysis to use of herbal or nonherbal medications only, similar results were obtained. Compared to other CAM domains, mind–body practice had the lowest prevalence of CAM use disclosure. Additionally, CAM use disclosure was significantly associated with higher HAART adherence. From this study, we showed that a high percentage of HIV-infected women did not discuss their CAM use with health care providers. Interventions targeted towards both physicians and patients may enhance communication of CAM use, avoid potential adverse events and drug interactions, and enhance HAART adherence.

doi:10.1089/apc.2009.0134

PMCID: PMC2801553 PMID: 19821723

7. Fracture incidence in HIV-infected women: results from the Women’s Interagency HIV Study

AIDS (London, England) 2010;24(17):2679-2686.

Background

The clinical importance of the association of HIV infection and antiretroviral therapy (ART) with low bone mineral density (BMD) in premenopausal women is uncertain because BMD stabilizes on established ART and fracture data are limited.

Methods

We measured time to first new fracture at any site with median follow-up of 5.4 years in 2391 (1728 HIV-infected, 663 HIV-uninfected) participants in the Women’s Interagency HIV Study (WIHS). Self-report of fracture was recorded at semiannual visits. Proportional hazard models assessed predictors of incident fracture.

Results

At baseline, HIV-infected women were older (40 ± 9 vs. 36 ± 10 years, P <0.0001), more likely to report postmenopausal status and be hepatitis C virus-infected, and weighed less than HIV-uninfected women. Among HIV-infected women, mean CD4+ cell count was 482 cells/μl; 66% were taking ART. Unadjusted incidence of fracture did not differ between HIV-infected and uninfected women (1.8 vs. 1.4/100 person-years, respectively, P = 0.18). In multivariate models, white (vs. African-American) race, hepatitis C virus infection, and higher serum creatinine, but not HIV serostatus, were statistically significant predictors of incident fracture. Among HIV-infected women, older age, white race, current cigarette use, and history of AIDS-defining illness were associated with incidence of new fracture.

Conclusion

Among predominantly premenopausal women, there was little difference in fracture incidence rates by HIV status, rather traditional risk factors were important predictors. Further research is necessary to characterize fracture risk in HIV-infected women during and after the menopausal transition.

doi:10.1097/QAD.0b013e32833f6294

PMCID: PMC3108019 PMID: 20859192

fracture; fragility fracture; HIV-infected women; premenopausal

8. Assessing the effect of HAART on change in quality of life among HIV-infected women

AIDS Research and Therapy 2006;3:6.

Background

The impact of highly active antiretroviral therapy (HAART) on health-related quality of life (QOL) of HIV-1 infected individuals in large prospective cohorts has not been well studied.

Objective

To assess the effect of HAART on QOL by comparing HIV-infected women using HAART with HIV-infected women remaining HAART naïve in the Women's Interagency HIV Study (WIHS), a multicenter prospective cohort study begun in 1994 in the US.

Methods

A 1:1 matching with equivalent (≤ 0.1%) propensity scores for predicting HAART initiation was implemented and 458 pairs were obtained. HAART effects were assessed using pattern mixture models. The changes of nine QOL domain scores and one summary score derived from a shortened version of the MOS-HIV from initial values were used as study outcomes.

Results

The background covariates of the treatment groups were well-balanced after propensity score matching. The 916 matched subjects had a mean age of 38.5 years and 42% had a history of AIDS diagnosis. The participants contributed a total of 4,292 person visits with a median follow-up time of 4 years. In the bivariate analyses with only HAART use and time as covariates, HAART was associated with short-term improvements of 4 QOL domains: role functioning, social functioning, pain and perceived health index. After adjusting for demographic, socioeconomic, biological and clinical variables, HAART had small but significant short-term improvements on changes in summary QOL (mean change: 3.25; P = 0.02), role functioning (6.99; P < 0.01), social functioning (5.74; P < 0.01), cognitive functioning (3.59; P = 0.03), pain (6.73; P < 0.01), health perception (3.67; P = 0.03) and perceived health index (4.87; P < 0.01). These QOL scores typically remained stable or declined over additional follow-up and there was no indication that HAART modified these trends.

Conclusion

Our study demonstrated significant short-term HAART effects on most QOL domains, but additional use of HAART did not modify long-term trends. These changes could be attributed to the direct effect of HAART and indirect HAART effect mediated through clinical changes.

doi:10.1186/1742-6405-3-6

PMCID: PMC1459186 PMID: 16549012

9. HIV As a Risk Factor for Lung Cancer in Women: Data From the Women's Interagency HIV Study

Journal of Clinical Oncology 2010;28(9):1514-1519.

Purpose

Prior reports of an increased risk of lung cancer in HIV-infected individuals have not always included control groups, nor considered other risk factors such as tobacco exposure. We sought to determine the role of HIV infection and highly active antiretroviral therapy (HAART) on lung cancer incidence in 2,651 HIV-infected and 898 HIV-uninfected women from the Women's Interagency HIV Study (WIHS).

Methods

A prospective study of the incidence rates of lung cancer was conducted, with cases identified through medical records, death certificates, and state cancer registries. Standardized incidence ratios (SIRs) were calculated to compare lung cancer incidence among HIV-infected and uninfected WIHS participants, with population-based expectations using the Surveillance, Epidemiology, and End Results registry. Behavioral characteristics in the WIHS were compared to US women by age and race adjusting the population-based data from the National Health and Nutritional Examination Survey (NHANES) III.

Results

Incidence rates of lung cancer were similar among HIV-infected and uninfected WIHS women. Lung cancer SIRs were increased in both HIV-infected and -uninfected women compared with population expectations, but did not differ by HIV status. Among HIV-infected women, lung cancer incidence rates were similar in pre-HAART and HAART eras. All WIHS women with lung cancer were smokers; the risk of lung cancer increased with cumulative tobacco exposure. WIHS women were statistically more likely to smoke than US women studied in NHANES III.

Conclusion

HIV infection is strongly associated with smoking behaviors that increase lung cancer risk. The role of HIV itself remains to be clarified.

doi:10.1200/JCO.2009.25.6149

PMCID: PMC2849771 PMID: 20177022

10. Prevalence and Correlates of Elevated Body Mass Index among HIV-Positive and HIV-Negative Women in the Women's Interagency HIV Study

AIDS Patient Care and STDs 2009;23(12):1009-1016.

Abstract

Since the introduction of highly active antiretroviral therapy (HAART) and the subsequent increased life expectancy in HIV-infected persons, non-HIV–related diseases have become an important cause of morbidity and mortality. This cross-sectional study reports the prevalence of overweight and obesity, and sociodemographic, psychological, and substance use-related risk factors for elevated body mass index (BMI) among 2157 HIV-seropositive (HIV+) in comparison to 730 HIV-seronegative (HIV−) participants in the Women's Interagency HIV Study (WIHS). Separate univariable and multivariate linear regression analyses were completed for HIV+ and HIV− women. Our study revealed a similar proportion of obesity (body mass index [BMI] ≥30) among HIV+ (33%) and HIV− women (29%) (p = 0.12), as well as comparable median BMI (HIV+: 26.1 versus HIV−: 26.7, p = 0.16). HIV+ compared to HIV− women, respectively, were significantly (p < 0.01) older (median = 35.6 versus. 32.5), but similar (p = 0.97) by race/ethnicity (57% African American, 28% Hispanic, and 15% white for both). In multivariate models for both HIV+ and HIV− women, African American race/ethnicity was significantly (p < 0.05) associated with higher BMI, while higher quality of life score and illicit hard drug use were associated with lower BMI. Additionally, smoking, alcohol use, markers of advanced HIV infection (AIDS diagnosis, elevated HIV viral load, low CD4 count), and a history of antiretroviral therapy use (ART) were also associated with lower BMI among HIV+ women. In conclusion, risk factors for elevated BMI were similar for HIV+ and HIV− women in the WIHS. For HIV+ women, all markers of advanced HIV infection and ART use were additionally associated with lower BMI.

doi:10.1089/apc.2009.0175

PMCID: PMC2832643 PMID: 19909168

11. Live birth patterns among HIV-infected women before and after the availability of HAART

American journal of obstetrics and gynecology 2007;196(6):541.e1-541.e6.

Objective

To investigate the relationship between HIV infection and childbearing before and after the availability of HAART.

Study Design

Enrollment in the Women’s Interagency HIV Study took place in 1994–1995 (pre-HAART era), and again in 2001–2002 (HAART era). Live birth rates prior to enrollment were compared between treatment era cohorts for HIV-infected and HIV-uninfected women aged 15–44 years using Poisson regression. For HIV-infected women we included live births between HIV diagnosis date and study entry; the HAART era cohort included only women diagnosed with HIV in 1996 and after.

Results

Among HIV-infected women, the HAART era live birth rate was 150% higher than in the pre-HAART era (p=.001), vs. a 5% increase among HIV-uninfected women. The rate of increase in live birth rate was higher for women ≥35 years (vs. <25, p=.02), and with >high school education (vs.

Conclusions

The availability of effective therapeutic interventions has profoundly impacted childbearing among HIV-infected women.

doi:10.1016/j.ajog.2007.01.005

PMCID: PMC1949426 PMID: 17547887

HIV; women; reproductive decision-making; birth rate; highly active antiretroviral therapy

12. Association Between Living With Children and Adherence to Highly Active Antiretroviral Therapy in the Women’s Interagency HIV Study

Pediatrics 2008;121(4):e787-e793.

OBJECTIVE

The purpose of this work was to evaluate whether living with children adversely affects adherence to highly active antiretroviral therapy in HIV-infected women.

PARTICIPANTS AND METHODS

We conducted a prospective cohort study between October 1998 and September 2005. The study outcome was ≥95% adherence to highly active antiretroviral therapy evaluated at 5832 semiannual visits among 1366 HIV-infected women in the Women’s Interagency HIV Study. The primary exposure defined at the visit immediately before outcome ascertainment was the number of children ≤18 years of age reported living in the household.

RESULTS

The percentage of women who reported ≥2 children in the household who also reported ≥95% adherence ranged from 68% to 75% compared with adherence when either 1 child or no children were reported. Each additional child reported living in the household was associated with a 6% decrease in the odds of ≥95% adherence.

CONCLUSION

The impact of living with a child on the ability to take medications by HIV-infected women has not been examined thoroughly. Our data suggest that adherence to highly active antiretroviral therapy is inversely associated with the number of children living in the household.

doi:10.1542/peds.2007-1586

PMCID: PMC2651400 PMID: 18381507

adherence; children; HAART; HIV

13. Brief Report: Plasma Homocysteine is Not Associated with HIV Serostatus or Antiretroviral Therapy in Women

Journal of acquired immune deficiency syndromes (1999) 2009;51(2):175-178.

Background

The effects of HIV serostatus and combination antiretroviral therapy (cART) on plasma homocysteine (Hcy) are uncertain.

Methods

Plasma Hcy was assayed in a cross-sectional study of 249 HIV-infected and 127 HIV-uninfected women at the Bronx Women’s Interagency HIV Study site.

Results

Mean plasma Hcy was 7.42 ± 2.68 in HIV-infected and 7.18 ± 2.66 µmol/L in HIV-uninfected women (P = 0.40). Hyperhomocysteinemia (defined as Hcy > 10 µmol/L) was seen in 16.9% and 13.4 % of HIV-infected and HIV-uninfected women, respectively (P=0.45). Among HIV-infected women, cART use was not associated with Hcy level. Compared to the lowest quartile, women with Hcy in the highest quartile had lower mean serum vitamin B12 and RBC folate levels. In multivariate analysis that did not include micronutrient levels, age, serum creatinine and lower CD4% were significantly associated with plasma Hcy level in HIV-infected women.

Conclusions

Plasma Hcy was not associated with HIV serostatus or use of cART in this cross-sectional study. Reduced availability of folate cofactors for Hcy remethylation in HIV-infected women with lower folate intake and decreased health status may influence Hcy levels.

doi:10.1097/QAI.0b013e3181a42bdf

PMCID: PMC2755615 PMID: 19333128

Homocysteine; HIV; women; vitamin B12; folate

14. An important clinical lesson from a patient infected with HIV with diabetic nephropathy and retinopathy

Martinelli, Pasquale | Agangi, Annalisa | Sansone, Matilde | Napolitano, Raffaele | Maruotti, Giuseppe Maria

BMJ Case Reports 2009;2009:bcr06.2008.0200.

In resource-rich settings, advances in antiretroviral therapy have reduced the morbidity and increased the life expectancy of patients infected with HIV and consequently increased the likelihood of observing other non-HIV-related diseases in this group of patients. We report a high-risk pregnancy in a 26-year-old woman infected with HIV with complicated insulin-dependent diabetes mellitus. Because of maternal concomitant disease and concerns regarding potential antiretroviral toxicity on maternal disease, an abbreviated regimen of zidovudine prophylaxis was offered to prevent neonatal infection. After the iatrogenic preterm delivery of a healthy and uninfected baby, the patient experienced vulvar oedema and she is now waiting for renal transplantation.

In conclusion, our case is one of a range of possible scenarios that may develop in pregnant women who are infected with HIV, reflecting the highly active antiretroviral therapy (HAART)-associated improvements in survival and health.

doi:10.1136/bcr.06.2008.0200

PMCID: PMC3029002 PMID: 21686901

15. ASSOCIATION OF COMPLEMENTARY AND ALTERNATIVE MEDICINE USE WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY INITIATION

Alternative therapies in health and medicine 2008;14(5):18-22.

Objective

To assess whether complementary and alternative medicine (CAM) use is associated with the timing of highly active antiretroviral therapy (HAART) initiation among human immunodeficiency virus (HIV)–infected participants of the Women’s Interagency HIV Study.

Study Methods

Prospective cohort study between January 1996 and March 2002. Differences in the cumulative incidence of HAART initiation were compared between CAM users and non–CAM users using a logrank test. Cox regression model was used to assess associations of CAM exposures with time to HAART initiation.

Main Outcome and Exposures

Study outcome was time from January 1996 to initiation of HAART. Primary exposure was use of any CAM modality before January 1996, and secondary exposures included the number and type of CAM modalities used (ingestible CAM medication, body practice, or spiritual healing) during the same period.

Results

One thousand thirty-four HIV-infected women contributed a total of 4987 person-visits during follow-up. At any time point, the cumulative incidence of HAART initiation among CAM users was higher than that among non–CAM users. After adjustment for potential confounders, those reporting CAM use were 1.34 times (95% confidence interval: 1.09, 1.64) more likely to initiate HAART than non–CAM users.

Conclusion

Female CAM users initiated HAART regimens earlier than non–CAM users. Initiation of HAART is an important clinical marker, but more research is needed to elucidate the role specific CAM modalities play in HIV disease progression.

PMCID: PMC2651402 PMID: 18780580

16. The Impact of Kidney Function at HAART Initiation on Mortality in HIV-infected Women

Journal of acquired immune deficiency syndromes (1999) 2010;55(2):217-220.

Background

In the early highly active antiretroviral therapy (HAART) era, kidney dysfunction was strongly associated with death among HIV-infected individuals. We re-examined this association in the later HAART period to determine whether chronic kidney disease (CKD) remains a predictor of death after HAART-initiation.

Methods

To evaluate the effect of kidney function at the time of HAART initiation on time to all-cause mortality, we evaluated 1415 HIV-infected women initiating HAART in the Women’s Interagency HIV Study (WIHS). Multivariable proportional hazards models with survival times calculated from HAART initiation to death were constructed; participants were censored at the time of the last available visit or December 31, 2006.

Results

CKD (eGFR <60 ml/min/1.73 m2) at HAART initiation was associated with higher mortality risk adjusting for age, race, hepatitis C serostatus, AIDS history and CD4+ cell count (hazard ratio [HR]=2.23, 95% confidence interval [CI]: 1.45–3.43). Adjustment for hypertension and diabetes history attenuated this association (HR=1.89, CI: 0.94–3.80). Lower kidney function at HAART initiation was weakly associated with increased mortality risk in women with prior AIDS (HR=1.09, CI: 1.00–1.19, per 20% decrease in eGFR).

Conclusions

Kidney function at HAART initiation remains an independent predictor of death in HIV-infected individuals, especially in those with a history of AIDS. Our study emphasizes the necessity of monitoring kidney function in this population. Additional studies are needed to determine mechanisms underlying the increased mortality risk associated with CKD in HIV-infected persons.

doi:10.1097/QAI.0b013e3181e674f4

PMCID: PMC3243740 PMID: 20581688

kidney disease; mortality; HIV; WIHS; antiretroviral therapy

17. Factors Associated with Poor Immunologic Response to Virologic Suppression by Highly Active Antiretroviral Therapy in HIV-Infected Women

AIDS research and human retroviruses 2006;22(3):222-231.

Virologic response to highly active antiretroviral therapy (HAART) typically results in a substantial rise in CD4 cell counts. We investigated factors associated with poor CD4 response among HIV-infected women followed at 6-monthly intervals in the Women’s Interagency HIV Study. Women with nadir CD4 counts <350 cells/mm3 who achieved at least 6 months of plasma HIV RNA < 400 copies/ml were studied. Demographic, clinical, and treatment factors were compared between immunologic nonresponders, defined as the lower quartile of CD4 count change after two visits with virologic suppression (<56 cell/mm3; n = 38), and the remaining group of responders (n = 115). Immunologic nonresponders had lower baseline HIV RNA levels and higher CD4 counts, more frequently used HAART 6 months prior to achieving consistent viral suppression, and more commonly had HIV RNA levels >80 but <400 copies/mL at both suppressive visits (21 vs. 7.8%, p = 0.024). In multivariate analysis, higher CD4 count and lower HIV RNA level at the last presuppressive visit were associated with immune nonresponse. We conclude that higher baseline CD4 count and lower HIV RNA level were associated with poor immunologic response to HAART in women with virologic suppression for at least 6 months. Persistent low level viremia may also contribute.

doi:10.1089/aid.2006.22.222

PMCID: PMC3126664 PMID: 16545008

18. Incidence and risk factors for verrucae in women

AIDS (London, England) 2008;22(10):1213-1219.

Objectives

To describe the incidence and risk factors for verrucae in HIV-infected and uninfected women.

Design and Methods

A prospective study of 1,790 HIV-infected and 772 uninfected women. Skin examinations and interviews were performed every six months over an 8-year study period. Data collected at each visit included antiretroviral therapy use since the prior visit, CD4 counts, HIV RNA loads, and location, description, and diagnosis of verrucae. Incidence rates of cutaneous and anogenital warts were determined.

Results

Unadjusted cumulative incidence of cutaneous warts for HIV-uninfected women was 6.6%, 6.7% for HIV-infected women who initiated HAART, and 8.4% for HIV-infected, HAART-naïve women. The unadjusted cumulative incidence of anogenital verrucae for HIV-uninfected women was 9.3%, 28.4% for HIV-infected women who initiated HAART, and 25.1% for HIV-infected women who were HAART-naïve. Multivariate proportional hazard models revealed the following significant factors for the development of cutaneous verrucae among HIV-infected women: Black race (RH=0.50) and Hispanic ethnicity (RH=0.38), compared to White race. Risk factors for anogenital verrucae were: more recent recruitment (RH=0.63), HPV infection at baseline (RH=1.85), decade of age (RH=0.82), current smoker (RH=1.40), lowest CD4 count (per 100 cells/mm3) in the past 4 years (RH=0.85), and log10 higher HIV viral load at the prior visit (RH=1.34).

Conclusions

HIV-infected women had a significantly increased cumulative incidence of anogenital verrucae compared to HIV-uninfected women. Although HAART did not alter the risk of developing skin or anogenital warts, those with higher CD4 cell counts and lower HIV RNA had a lower risk of developing anogenital warts.

doi:10.1097/QAD.0b013e3283021aa3

PMCID: PMC2615554 PMID: 18525267

HAART; HIV infection; incidence; risk factors; verrucae; women

19. Association of Race, Substance Abuse, and Health Insurance Coverage With Use of Highly Active Antiretroviral Therapy Among HIV-Infected Women, 2005

American journal of public health 2009;100(8):1493-1499.

Objectives

We examined racial/ethnic disparities in highly active antiretroviral therapy (HAART) use and whether differences are moderated by substance use or insurance status, using data from the Women’s Interagency HIV Study (WIHS).

Methods

Logistic regression examined HAART use in a longitudinal cohort of women for whom HAART was clinically indicated in 2005 (N=1354).

Results

Approximately 3 of every 10 eligible women reported not taking HAART. African American and Hispanic women were less likely than were White women to use HAART. After we adjusted for potential confounders, the higher likelihood of not using HAART persisted for African American but not for Hispanic women. Uninsured and privately insured women, regardless of race/ethnicity, were less likely than were Medicaid enrollees to use HAART. Although alcohol use was related to HAART nonuse, illicit drug use was not.

Conclusions

These findings suggest that expanding and improving insurance coverage should increase access to antiretroviral therapy across racial/ethnic groups, but it is not likely to eliminate the disparity in use of HAART between African American and White women with HIV/AIDS.

doi:10.2105/AJPH.2008.158949

PMCID: PMC2901300 PMID: 19910347

20. Evaluating the Impact of Hepatitis C Virus (HCV) on Highly Active Antiretroviral Therapy–Mediated Immune Responses in HCV/HIV-Coinfected Women: Role of HCV on Expression of Primed/Memory T Cells

The Journal of infectious diseases 2006;193(9):1202-1210.

Objective

To evaluate the impact of hepatitis C virus (HCV) on the immune system before receipt of highly active antiretroviral therapy (HAART) and on immune recovery after receipt of HAART among human immunodeficiency virus (HIV)/HCV–coinfected women enrolled in the Women’s Interagency HIV Study.

Methods

The study included 294 HIV-infected women who initiated HAART and attended 2 follow-up visits. The women were grouped on the basis of positive HCV antibody and HCV RNA tests. There were 148 women who were HCV antibody negative, 34 who were HCV antibody positive but RNA negative, and 112 who were HCV antibody and RNA positive. Immune recovery was measured by flow-cytometric assessment for markers of activation and maturation on CD4+ and CD8+ T cells. Data analysis used repeated measures of variance.

Results

HIV/HCV coinfection is associated with an increased number of CD4+ and CD8+ primed/memory T cells. HIV/HCV coinfection, however, did not affect any further decreases in CD4+ or CD4+ and CD8+ naive/memory T cell counts or enhanced T cell activation. HIV/HCV coinfection also did not affect HAART responses in the CD4+ and CD8+ T cell compartment.

Conclusions

HCV does not affect immune responses to HAART in HIV/HCV–coinfected individuals but is associated with an expansion of CD4+ and CD8+ memory T cell subsets. Functional impairment in the CD4+ and CD8+ T cell compartments still needs to be assessed in coinfected patients.

doi:10.1086/500843

PMCID: PMC3126663 PMID: 16586355

21. Prevalence of Abnormalities in Vestibular Function and Balance among HIV-Seropositive and HIV-Seronegative Women and Men

PLoS ONE 2012;7(5):e38419.

Background

Most HIV-seropositive subjects in western countries receive highly active antiretroviral therapy (HAART). Although many aspects of their health have been studied, little is known about their vestibular and balance function. The goals of this study were to determine the prevalences of vestibular and balance impairments among HIV-seropositive and comparable seronegative men and women and to determine if those groups differed.

Methods

Standard screening tests of vestibular and balance function, including head thrusts, Dix-Hallpike maneuvers, and Romberg balance tests on compliant foam were performed during semiannual study visits of participants who were enrolled in the Baltimore and Washington, D. C. sites of the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study.

Results

No significant differences by HIV status were found on most tests, but HIV-seropositive subjects who were using HAART had a lower frequency of abnormal Dix-Hallpike nystagmus than HIV-seronegative subjects. A significant number of nonclassical Dix-Hallpike responses were found. Age was associated with Romberg scores on foam with eyes closed. Sex was not associated with any of the test scores.

Conclusion

These findings suggest that HAART-treated HIV infection has no harmful association with vestibular function in community-dwelling, ambulatory men and women. The association with age was expected, but the lack of association with sex was unexpected. The presence of nonclassical Dix-Hallpike responses might be consistent with central nervous system lesions.

doi:10.1371/journal.pone.0038419

PMCID: PMC3364989 PMID: 22675462

22. Low CD4+ T cell count as a major atherosclerosis risk factor in HIV-infected women and men

AIDS (London, England) 2008;22(13):1615-1624.

Objective

To assess the association of HIV infection, HIV disease parameters (including CD4+ T-cell counts, HIV viral load, and AIDS) and antiretroviral medication use with subclinical carotid artery atherosclerosis.

Design

Cross-sectional study nested within a prospective cohort study

Methods

Among participants in the Women's Interagency HIV Study (1,331 HIV-infected women, 534 HIV-uninfected women) and Multicenter AIDS Cohort Study (600 HIV-infected men, 325 HIV-uninfected men), we measured subclinical carotid artery lesions and common carotid artery intima-media thickness (CIMT) using B-mode ultrasound. We estimated adjusted mean CIMT differences and prevalence ratios (PRs) for carotid lesions associated with HIV-related disease and treatments, with multivariate adjustment to control for possible confounding variables.

Results

Among HIV-infected individuals, a low CD4+ T cell count was independently associated with an increased prevalence of carotid lesions. Compared to the reference group of HIV-uninfected individuals, the adjusted PR for lesions among HIV-infected individuals with CD4+ T-cell count <200 cells/mm3 was 2.00 (95% confidence interval 1.22, 3.28) in women and 1.74 (95% confidence interval 1.04, 2.93) in men. No consistent association of antiretroviral medications with carotid atherosclerosis was observed, except for a borderline significant association between protease inhibitor use and carotid lesions in men (with no association among women). History of clinical AIDS and HIV viral load were not significantly associated with carotid atherosclerosis.

Conclusions

Beyond traditional cardiovascular disease risk factors, low CD4+ T-cell count is the most robust risk factor for increased subclinical carotid atherosclerosis in HIV-infected women and men.

doi:10.1097/QAD.0b013e328300581d

PMCID: PMC2624572 PMID: 18670221

23. INCREASED INCIDENCE OF ASTHMA IN HIV-INFECTED CHILDREN TREATED WITH HAART IN THE NIH WOMEN AND INFANTS TRANSMISSION STUDY

The Journal of allergy and clinical immunology 2008;122(1):159-165.

BACKGROUND

Immunoreconstitution of HIV-infected (HIV+) patients after treatment with highly antiretroviral therapy (HAART) appears to provoke inflammatory diseases.

OBJECTIVE

Determine whether HIV+ children on HAART (HIV+ HAART+) have a higher incidence of asthma than HIV+ children not on HAART (HIV+ HAART−).

METHODS

To investigate this possibility, 2,664 children (193 HIV+, 2,471 HIV−) born to HIV+ women were evaluated for the incidence and prevalence of asthma (i.e., asthma medication use), and change of CD4+ T cell percentage with time.

RESULTS

The HIV+ HAART+ children had higher CD4+ T cell percentages, lower CD8+ T cell percentages, and lower viral burdens than the HIV+ HAART− children (P≤0.05 to P≤0.01). The cumulative incidence of asthma medication use in HIV+ HAART+ children at 13.5 year rose to 33.5% vs. 11.5% in HIV+ HAART− children (hazard ratio=3.34, P=0.01) and was equal to that in the HIV− children. In children born prior to the HAART era, the prevalence of asthma medication use for HIV+ HAART+ children at 11 years of age was 10.4% vs. 3.8% for HIV+ HAART− children (odds ratio=3.38, P=0.02) and was equal to that of the HIV− children. The rate of change of CD4+ T cells (percent/year) around the time of first asthma medication for HIV+ HAART+ vs. HIV+ HAART− children was 0.81 vs. −1.43 (P=0.01).

CONCLUSION

The increased incidence of asthma in HIV+ HAART+ children may be driven by immunoreconstitution of CD4+ T cells.

CLINICAL IMPLICATIONS

This HIV model of pediatric asthma may yield clues to help explain the epidemic of asthma in the general pediatric population.

doi:10.1016/j.jaci.2008.04.043

PMCID: PMC3246282 PMID: 18547627

pediatric HIV infection; CD4+ T cell mediated induction of asthma; HAART-produced immunoreconstitution

24. The Impact of the AIDS Drug Assistance Program (ADAP) on Use of Highly Active Antiretroviral and Antihypertensive Therapy among HIV-Infected Women

Journal of acquired immune deficiency syndromes (1999) 2011;56(3):253-262.

Objectives

To evaluate the association between enrollment into an AIDS Drug Assistance Program (ADAP) and use of highly active antiretroviral therapy (HAART) and antihypertensive therapy.

Methods

Cross-sectional analyses of data were performed on HAART-eligible women enrolled in the California (n=439), Illinois (n=168), and New York (n=487) Women’s Interagency HIV Study (WIHS) sites. A subset of HIV-infected women with hypertension (n=395) was also analyzed. Unadjusted and adjusted backward stepwise elimination logistic regression measured the association between demographic, behavioral, and health service factors and non-use of HAART or antihypertensive medication.

Results

In adjusted analysis of HAART non-use, women without ADAP were significantly more likely not to use HAART (odds ratio [OR] = 2.4, 95% confidence interval [CI] = 1.5–3.7) than women with ADAP. In adjusted analysis of antihypertensive medication non-use, women without ADAP had an increased but not significant odds of antihypertensive medication non-use (OR = 2.4, 95% CI = 0.93–6.0) than women with ADAP.

Conclusions

Government-funded programs for prescription drug coverage, such as ADAP, may play an important role in how HIV-positive women to access and use essential medications for chronic diseases.

doi:10.1097/QAI.0b013e31820a9d04

PMCID: PMC3042745 PMID: 21239994

AIDS; antiretroviral therapy; hypertension; women; healthcare disparity; prescription insurance

25. Sex Hormones, Insulin Resistance, and Diabetes Mellitus among Men with or at Risk for HIV Infection

Journal of acquired immune deficiency syndromes (1999) 2011;58(2):173-180.

Objective

To examine the relationship of free testosterone (FT) and sex hormone-binding globulin (SHBG) with insulin resistance and diabetes mellitus (DM) in HIV disease.

Design

Cross-sectional analysis from 322 HIV-uninfected and 534 HIV-infected men in the Multicenter AIDS Cohort Study.

Methods

The main outcomes were DM and Homeostasis model assessment–insulin resistance (HOMA-IR). DM was defined as fasting serum glucose (FG) ≥ 126 or self-reported DM and use of DM medications. Homeostasis model assessment–insulin resistance (HOMA-IR) was calculated from FG and fasting insulin.

Results

Compared with HIV-uninfected men in our sample, HIV-infected men were younger, with lower BMI, and more often black. HIV-infected men had lower FT (p < 0.001) and higher SHBG (p < 0.0001). The adjusted odds ratio for DM was 1.98 (95% CI 1.04–3.78); mean adjusted log HOMA-IR was 0.21 units higher in HIV-infected men (p < 0.0001). Log SHBG, but not log FT, was associated with DM (OR = 0.44, 95% CI 0.25, 0.80) in both groups. Log FT and log SHBG were inversely related to insulin resistance (p < 0.05 for both) independent of HIV.

Conclusions

Compared to HIV-uninfected men, HIV-infected men had lower FT, higher SHBG, and more insulin resistance and DM. Lower FT and lower SHBG were associated with insulin resistance regardless of HIV serostatus. This suggests that sex hormones play a role in the pathogenesis of glucose abnormalities among HIV-infected men.

doi:10.1097/QAI.0b013e3182278c09

PMCID: PMC3175332 PMID: 21705912

Testosterone; Sex Hormone-Binding Globulin; Insulin Resistance; Diabetes Mellitus; HIV

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