Predicting death over 8 years in a prospective cohort of HIV-infected women: the Women's Interagency HIV Study.

ObjectivesPredicting mortality in middle-aged HIV-infected (HIV+) women on antiretroviral therapies (ART) is important for understanding the impact of HIV infection. Several health indices have been used to predict mortality in women with HIV infection. We evaluated: (1) an HIV biological index, Veterans Aging Cohort Study (VACS); (2) a physical index, Fried Frailty Index (FFI); and (3) a mental health index, Center for Epidemiologic Studies-Depression (CES-D). Proportional hazards regression analyses were used to predict death and included relevant covariates.DesignProspective, observational cohort.SettingMulticentre, across six sites in the USA.Participants1385 multirace/ethnic ART-experienced HIV+ women in 2005.Primary and secondary outcomesAll deaths, AIDS deaths and non-AIDS deaths up to ~8 years from baseline.ResultsIncluded together in one model, VACS Index was the dominant, significant independent predictor of all deaths within 3 years (HR=2.20, 95% CI 1.83, 2.65, χ2=69.04, p<0.0001), and later than 3 years (HR=1.55, 95% CI 1.30, 1.84, χ2=23.88, p<0.0001); followed by FFI within 3 years (HR=2.06, 95% CI 1.19, 3.57, χ2=6.73, p=0.01) and later than 3 years (HR=2.43, 95% CI 1.58, 3.75, χ2=16.18, p=0.0001). CES-D score was not independently associated with mortality.Conclusions and relevanceThis is the first simultaneous evaluation of three common health indices in HIV+ adults. Indices reflecting physical and biological ageing were associated with death

Positive affect and its association with viral control among women with HIV infection.

We assessed the relationship between positive affect and viral suppression among women with HIV infection

Computational Modeling Reveals Distinct Effects of HIV and History of Drug Use on Decision-Making Processes in Women

Objective: Drug users and HIV-seropositive individuals often show deficits in decision-making; however the nature of these deficits is not well understood. Recent studies have employed computational modeling approaches to disentangle the psychological processes involved in decision-making. Although such approaches have been used successfully with a number of clinical groups including drug users, no study to date has used computational modeling to examine the effects of HIV on decision-making. In this study, we use this approach to investigate the effects of HIV and drug use on decision making processes in women, who remain a relatively understudied population. Method: Fifty-seven women enrolled in the Women’s Interagency HIV Study (WIHS) were classified into one of four groups based on their HIV status and history of crack cocaine and/or heroin drug use (DU): HIV+/DU+ (n = 14); HIV+/DU2 (n = 17); HIV2/DU+ (n = 14); and HIV2/DU2 (n = 12). We measured decision-making with the Iowa Gambling Task (IGT) and examined behavioral performance and model parameters derived from the best-fitting computational model of the IGT. Results: Although groups showed similar behavioral performance, HIV and DU exhibited differential relationship to model parameters. Specifically, DU was associated with compromised learning/memory and reduced loss aversion, whereas HIV was associated with reduced loss aversion, but was not related to other model parameters. Conclusions: Results reveal that HIV and DU have differential associations with distinct decision-making processes in women. This study contributes to a growing line of literature which shows that different psychological processes may underlie similar behavioral performance in various clinical groups and may be associated with distinct functional outcomes

Patterns and rates of viral evolution in HIV-1 subtype B infected females and males.

Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS. However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men. We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART). This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes. No differences in ensuing nucleotide substitution rates were found between the female and male cohorts studied herein. As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region. These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men

Risk Factors for Cervical Precancer and Cancer in HIV-Infected, HPV-Positive Rwandan Women

Background: Although cervical cancer is an AIDS-defining condition, infection with human immunodeficiency virus (HIV) may only modestly increase the risk of cervical cancer. There is a paucity of information regarding factors that influence the natural history of human papillomavirus (HPV) in HIV-infected women. We examined factors associated with cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in Rwandan women infected with both HIV and HPV (HIV+/HPV+).Methods: In 2005, 710 HIV+ Rwandan women ≥25 years enrolled in an observational cohort study; 476 (67%) tested HPV+. Each woman provided sociodemographic data, CD4 count, a cervical cytology specimen and cervicovaginal lavage (CVL), which was tested for >40 HPV genotypes by MY09/MY11 PCR assay. Logistic regression models calculated odds ratios (OR) and 95% confidence intervals (CI) of associations of potential risk factors for CIN3+ among HIV+/HPV+ women.Results: Of the 476 HIV+/HPV+ women 42 (8.8%) were diagnosed with CIN3+. Factors associated with CIN3+ included ≥7 (vs. 0-2) pregnancies, malarial infection in the previous six months (vs. never), and ≥7 (vs. 0-2) lifetime sexual partners. Compared to women infected by non-HPV16 carcinogenic HPV genotypes, HPV16 infection was positively associated and non-carcinogenic HPV infection was inversely associated with CIN3+. CD4 count was significantly associated with CIN3+ only in analyses of women with non-HPV16 carcinogenic HPV (OR = 0.62 per 100 cells/mm3, CI = 0.40-0.97).Conclusions: In this HIV+/HPV+ population, lower CD4 was significantly associated with CIN3+ only in women infected with carcinogenic non-HPV16. We found a trend for higher risk of CIN3+ in HIV+ women reporting recent malarial infection; this association should be investigated in a larger group of HIV+/HPV+ women.</p

Comparison of antibodies that mediate HIV type 1 gp120 antibody-dependent cell-mediated cytotoxicity in asymptomatic HIV type 1-positive men and women

Recent studies suggest that HIV-specific antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies contribute to protective immunity against HIV. An important characteristic of future HIV vaccines will, therefore, be the ability to stimulate production of these antibodies in both men and women. Early studies suggest that men may have a better ADCC antibody response against HIV than women. Our objective was to determine whether men and women differ with respect to their ADCC response to HIV-1 gp120. HIV-positive, asymptomatic untreated men and women were matched for race, age, CD4(+) T cell number, HIV-1 viral load, and treatment and HIV-1 gp120 ADCC antibody titers were compared. A standard (51)Cr-release assay was used to determine HIV-1 gp120 ADCC antibody titers in HIV-1-seropositive individuals from the Multicenter AIDS Cohort Study (MACS; n=32) and the Women's Interagency HIV Study (WIHS; n=32). Both sexes had high ADCC titers against HIV-1 gp120: 34.4% (n=11) and 40.6% (n=13) of men and women, respectively, had titers of 10,000; 62.5% (n=20) and 56.3% (n=18) had titers of 100,000. Groups did not differ in percent specific release (% SR), lytic units (LU), correlations of titer to viral load, or titer to CD4(+) T cells in men or women. Both groups also had similar cross-clade ADCC antibody responses (p>0.5 for % SR and LU). Comparable groups of asymptomatic HIV-1-infected men and women had comparable HIV-1 gp120 ADCC antibodies. Both sexes had significant cross-clade reactivity. Differences between men and women may become evident as disease progresses; this should be evaluated at later stages of HIV-1 infection

Mechanisms for the Negative Effects of Internalized HIV-Related Stigma on Antiretroviral Therapy Adherence in Women: The Mediating Roles of Social Isolation and Depression

Internalization of HIV-related stigma may inhibit a person's ability to manage HIV disease through adherence to treatment regimens. Studies, mainly with white men, have suggested an association between internalized stigma and suboptimal adherence to antiretroviral therapy (ART). However, there is a scarcity of research with women of different racial/ethnic backgrounds and on mediating mechanisms in the association between internalized stigma and ART adherence

Utilization of Alcohol Treatment Among HIV-Positive Women with Hazardous Drinking

Hazardous alcohol consumption has been frequently reported among women with HIV infection and is associated with a variety of negative health consequences. Treatments to reduce alcohol use may bring in health benefits. However, little is known regarding the utilization of alcohol treatment services among HIV+ women with hazardous drinking. Using data from the Women’s Interagency HIV Study (WIHS), this study assessed utilization of any alcohol treatment in the past 6 months and performed multivariable logistic regression to determine correlates of receipt of any alcohol treatment. Among 474 HIV+ women reporting recent hazardous drinking, less than one in five (19%) reported recent utilization of any alcohol treatment. Alcoholics Anonymous (AA) was the most commonly reported (12.9%), followed by inpatient detoxification (9.9%) and outpatient alcohol treatment program (7.0%). Half (51%) receiving any alcohol treatment reported utilization of multiple treatments. Multivariable analyses found alcohol treatment was more often utilized by those who had social support (Odds ratio [OR]=1.68, 95% Confidence Interval [CI]=1.00 to 2.83), fewer economic resources (income $12,000, OR = 3.10, 95% CI=1.53 to 6.27), higher levels of drinking (16–35 drinks/week vs. 12–15 drinks/week, OR=3.02, 95% CI=1.47 to 6.21; 36+ drinks/week vs. 12–15 drinks/week, OR=4.41, 95% CI=2.03 to 9.59), and those who reported any illicit drug use (OR=2.77, 95% CI=1.44 to 5.34). More efforts are needed to enhance the utilization of alcohol treatment. Our findings highlight the unique profile of those who utilized alcohol treatment. Such information is vital to improve treatment delivery to address unmet need in this particular population

Effects of Antiretroviral Therapy and Depressive Symptoms on All-Cause Mortality Among HIV-Infected Women

Abstract Depression affects up to 30% of human immunodeficiency virus (HIV)-infected individuals. We estimated joint effects of antiretroviral therapy (ART) initiation and depressive symptoms on time to death using a joint marginal structural model and data from a cohort of HIV-infected women from the Women's Interagency HIV Study (conducted in the United States) from 1998–2011. Among 848 women contributing 6,721 years of follow-up, 194 participants died during follow-up, resulting in a crude mortality rate of 2.9 per 100 women-years. Cumulative mortality curves indicated greatest mortality for women who reported depressive symptoms and had not initiated ART. The hazard ratio for depressive symptoms was 3.38 (95% confidence interval (CI): 2.15, 5.33) and for ART was 0.47 (95% CI: 0.31, 0.70). Using a reference category of women without depressive symptoms who had initiated ART, the hazard ratio for women with depressive symptoms who had initiated ART was 3.60 (95% CI: 2.02, 6.43). For women without depressive symptoms who had not started ART, the hazard ratio was 2.36 (95% CI: 1.16, 4.81). Among women reporting depressive symptoms who had not started ART, the hazard ratio was 7.47 (95% CI: 3.91, 14.3). We found a protective effect of ART initiation on mortality, as well as a harmful effect of depressive symptoms, in a cohort of HIV-infected women