Mary Young

Whether widespread use of HAART changed patterns of HIV status disclosure among women living with HIV is largely unknown. In addition, the association between time to first HIV disclosure and depression has not been fully explored among women. A retrospective cross-sectional survey was conducted among HIV-infected women from the Washington, DC site of the Women’s Interagency HIV Study to collect detailed information about their HIV status disclosure behavior. A sample of 202 HIV-positive women, 102 diagnosed prior to and 100 post-HAART era participated in this study. Relationships between treatment era when diagnosed (pre-HAART or HAART era) and patterns of HIV status disclosure, and associations between HIV status disclosure and depression level were examined using generalized linear regression models with generalized estimating equation to adjust for repeated measurements from the same individuals. Our analyses showed that treatment era was not associated with either comfort level of HIV status disclosure or time to first HIV disclosure to either family members or friends. However, women were less likely to disclose HIV status to their family members in the HAART era (P = 0.006) after adjusting for social network type, comfort level of disclosure, time to first disclosure and length of follow-up time. In addition, longer time to first HIV disclosure, but not comfort level or extent of HIV status disclosure, was independently associated with depression levels as measured by CES-D score at study enrollment (“a few months after” vs “within a few days”: P = 0.008). More definitive studies utilizing longitudinal designs should be conducted to further examine impact of HAART era on HIV status disclosure and effect of HIV status disclosure on mental health.

An HIV-1 tropism test is recommended prior to CCR5 antagonist administration to exclude patients harboring non-R5 virus from treatment with this class of antiretrovirals. HIV-1 tropism determination based on proviral DNA (pvDNA) may be useful in individuals with plasma viral RNA suppression. We developed a genotypic tropism assay for pvDNA and assessed its performance in a retrospective analysis of samples collected longitudinally. We randomly selected paired plasma/PBMC samples from the Women’s Interagency HIV Study with plasma viral load ≥5,000 cp/mL at time 1 (T1), undetectable viral load maintained for ≥1 year and CD4+ >200 cells/μL at time 2 (T2). pvDNA was isolated from cryopreserved PBMCs. Sequences were analyzed in triplicate from 49/50 women, with tropism assigned using the geno2pheno (g2p) algorithm. The median time between T1 and T2 was 4.1 years. CXCR4-using virus was detected in 24% of the RNA samples and 33% of the pvDNA samples at T1, compared to 37% of the pvDNA samples at T2. Concordance between plasma RNA and pvDNA tropism was 88% at T1 and 80% at T2. The g2p scores for RNA (T1) vs DNA (T1, T2) were strongly correlated (Spearman rho: 0.85 (T1); 0.78 (T2)). In women with evidence of tropism switch at T2 (either R5 to non-R5 or non-R5 to R5), there was a correlation between change in tropism and time. Mean pvDNA viral load decreased by 0.4 log10 copies/106 cells between T1 and T2 (p < 0.0001), but this decrease was not significantly associated with tropism status. We demonstrated that pvDNA tropism in women with HIV-1 suppression is concordant with prior RNA tropism results, even after a median time of >4 years. pvDNA tropism testing may be useful to determine eligibility of patients with viral suppression to switch to a CCR5-antagonist based regimen as well as for research purposes.

Herpes zoster (HZ) is common among HIV-infected individuals, but the impacts of highly active antiretroviral therapy (HAART) and HAART adherence on HZ risk have not been well studied.

Rationale/statement of the problem : Acute and chronic stress is commonly reported by HIV-seropositive (HIV + ) individuals and may contribute to cognitive dysfunction that interferes with treatment adherence and daily functioning. Here we present data from two studies aimed at characterizing the effects of stress and stress hormones on cognition in HIV+ women. Methods : Six hundred and forty-five HIV+ and 345 at risk HIV-, predominantly African-American participants of the Womens Interagency HIV Study (WIHS), completed the 10 item Perceived Stress Scale (PSS-10) and a comprehensive neurocognitive test battery including measures of verbal learning and memory, verbal fluency, psychomotor speed, executive function, fine motor skills, working memory, attention, and concentration. High stress was defined by scores in the top quartile. Salivary cortisol levels were assessed concurrently with the neurocognitive battery and PSS-10 in 25 HIV+ women as a pilot at the Chicago WIHS. Results : After adjusting for relevant demographic and behavioral characteristics, HIV+ women performed worse than HIV- women on measures of verbal learning, memory and attention (ps < 0.05). High stress was negatively associated with measures of both attention and executive function (ps < 0.05). There was a significant interaction between HIV status and perceived stress on verbal memory (p=0.02). Among HIV+ women, those with high stress performed worse on verbal memory compared to women with low stress (β = 1.89, SE = 0.74, p=0.01). Conversely, among HIV- women, there was no difference in verbal memory performance by stress level (β = 0.73, SE = 0.99, p=0.46). There were no significant interactions between stress and HIV status on executive functioning, attention, fine motor skills, or processing speed. In HIV+ women, cortisol levels were not correlated with most outcomes, though levels were marginally associated with working memory (r = 0.37, p=0.08) which was likely attributable to women with high (r= 0.55, p=0.03) not low stress. Conclusion : Our findings indicate that HIV is associated with verbal memory difficulties among women and that high perceived stress may exacerbate the effect of HIV infection on poor memory performance. Longitudinal assessments are underway to determine the robustness of these associations

Background: The search for disease biomarkers within human peripheral fluids has become a favorable approach to preventative therapeutics throughout the past few years. The comparison of normal versus disease states can identify an overexpression or a suppression of critical proteins where illness has directly altered a patient's cellular homeostasis. In particular, the analysis of HIV-1 infected serum is an attractive medium with which to identify altered protein expression due to the ease and non-invasive methods of collecting samples as well as the corresponding insight into thein vivointeraction of the virus with infected cells/tissue. The utilization of proteomic techniques to globally identify differentially expressed serum proteins in response to HIV-1 infection is a significant undertaking that is complicated due to the innate protein profile of human serum.Results: Here, the depletion of 12 of the most abundant serum proteins, followed by two-dimensional gel electrophoresis coupled with identification of these proteins using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, has allowed for the identification of differentially expressed, low abundant serum proteins. We have analyzed and compared serum samples from HIV-1 infected subjects who are being treated using highly active antiretroviral therapy (HAART) to those who are latently infected but have not progressed to AIDS despite the absence of treatment, i.e. long term non-progressors (LTNPs). Here we have identified unique serum proteins that are differentially expressed in LTNP HIV-1 patients and may contribute to the ability of these patients to combat HIV-1 infection in the absence of HAART. We focused on the cdk4/6 cell cycle inhibitor p16^INK4Aand found that the treatment of HIV-1 latently infected cell lines with p16^INK4Adecreases viral production despite it not being expressed endogenously in these cells.Conclusions: Identification of these unique proteins may serve as an indication of altered viral states in response to infection as well as a natural phenotypic variability in response to HIV-1 infection in a given population.

To explore the relationship between vitamin A (retinol) deficiency and cervical squamous intraepithelial lesions (SILs) in human immunodeficiency virus (HIV)—infected women, we measured serum retinol concentrations in 1314 women enrolled in the Women's Interagency HIV Study and correlated the results with concurrent cervical cytology. At the baseline visit, 204 (15.5%) of the 1314 patients had retinol concentrations consistent with deficiency (P = .04) in a multivariate model, which included human papillomavirus (HPV) status and markers of nutritional status and HIV disease stage. In the subset of women with genital HPV (n = 774), a multivariate analysis again revealed a significant independent association between retinol P = .02). Our findings suggest that retinol deficiency may contribute to the development of cervical SILs in HIV-infected women.