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.
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.
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.
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.
atherosclerosis; cardiovascular disease; carotid arteries; HIV; epidemiology
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.
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.
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.
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.
fracture; fragility fracture; HIV-infected women; premenopausal
To investigate the relationship between HIV infection and childbearing before and after the availability of HAART.
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.
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.
The availability of effective therapeutic interventions has profoundly impacted childbearing among HIV-infected women.
HIV; women; reproductive decision-making; birth rate; highly active antiretroviral therapy
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.
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.
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.
adherence; children; HAART; HIV
The effects of HIV serostatus and combination antiretroviral therapy (cART) on plasma homocysteine (Hcy) are uncertain.
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.
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.
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.
Homocysteine; HIV; women; vitamin B12; folate
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.
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.
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.
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.
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.
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.
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.
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).
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.
kidney disease; mortality; HIV; WIHS; antiretroviral therapy
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.
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.
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).
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.
HAART; HIV infection; incidence; risk factors; verrucae; women
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).
Logistic regression examined HAART use in a longitudinal cohort of women for whom HAART was clinically indicated in 2005 (N=1354).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Cross-sectional study nested within a prospective cohort study
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.
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.
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.
Immunoreconstitution of HIV-infected (HIV+) patients after treatment with highly antiretroviral therapy (HAART) appears to provoke inflammatory diseases.
Determine whether HIV+ children on HAART (HIV+ HAART+) have a higher incidence of asthma than HIV+ children not on HAART (HIV+ HAART−).
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.
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).
The increased incidence of asthma in HIV+ HAART+ children may be driven by immunoreconstitution of CD4+ T cells.
This HIV model of pediatric asthma may yield clues to help explain the epidemic of asthma in the general pediatric population.
pediatric HIV infection; CD4+ T cell mediated induction of asthma; HAART-produced immunoreconstitution
To evaluate the association between enrollment into an AIDS Drug Assistance Program (ADAP) and use of highly active antiretroviral therapy (HAART) and antihypertensive therapy.
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.
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.
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.
AIDS; antiretroviral therapy; hypertension; women; healthcare disparity; prescription insurance
To examine the relationship of free testosterone (FT) and sex hormone-binding globulin (SHBG) with insulin resistance and diabetes mellitus (DM) in HIV disease.
Cross-sectional analysis from 322 HIV-uninfected and 534 HIV-infected men in the Multicenter AIDS Cohort Study.
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.
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.
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.
Testosterone; Sex Hormone-Binding Globulin; Insulin Resistance; Diabetes Mellitus; HIV