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Antiretroviral (ARV) drug use was analyzed in HIV-uninfected women in an observational cohort study conducted in 10 urban and periurban communities in the United States with high rates of poverty and HIV infection. Plasma samples collected in 2009-2010 were tested for the presence of 16 ARV drugs. ARV drugs were detected in samples from 39 (2%) of 1,806 participants: 27/181 (15%) in Baltimore, MD and 12/179 (7%) in Bronx, NY. The ARV drugs detected included different combinations of non-nucleoside reverse transcriptase inhibitors and protease inhibitors (1-4 drugs/sample). These data were analyzed in the context of self-reported data on ARV drug use. None of the 39 women who had ARV drugs detected reported ARV drug use at any study visit. Further research is needed to evaluate ARV drug use by HIV-uninfected individuals.

Multiassay algorithms (MAAs) can be used to estimate cross-sectional HIV incidence. We previously identified a robust MAA that includes the BED capture enzyme immunoassay (BED-CEIA), the Bio-Rad Avidity assay, viral load, and CD4 cell count. In this report, we evaluated MAAs that include a high-resolution melting (HRM) diversity assay that does not require sequencing. HRM scores were determined for eight regions of the HIV genome (2 in gag, 1 in pol, and 5 in env). The MAAs that were evaluated included the BED-CEIA, the Bio-Rad Avidity assay, viral load, and the HRM diversity assay, using HRM scores from different regions and a range of region-specific HRM diversity assay cutoffs. The performance characteristics based on the proportion of samples that were classified as MAA positive by duration of infection were determined for each MAA, including the mean window period. The cross-sectional incidence estimates obtained using optimized MAAs were compared to longitudinal incidence estimates for three cohorts in the United States. The performance of the HRM-based MAA was nearly identical to that of the MAA that included CD4 cell count. The HRM-based MAA had a mean window period of 154 days and provided cross-sectional incidence estimates that were similar to those based on cohort follow-up. HIV diversity is a useful biomarker for estimating HIV incidence. MAAs that include the HRM diversity assay can provide accurate HIV incidence estimates using stored blood plasma or serum samples without a requirement for CD4 cell count data.

Background: A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently developed for cross-sectional HIV incidence estimation. We evaluated the performance of the LAg-Avidity assay alone and in multi-assay algorithms (MAAs) that included other biomarkers., Methods and Findings: Performance of testing algorithms was evaluated using 2,282 samples from individuals in the United States collected 1 month to >8 years after HIV seroconversion. The capacity of selected testing algorithms to accurately estimate incidence was evaluated in three longitudinal cohorts. When used in a single-assay format, the LAg-Avidity assay classified some individuals infected >5 years as assay positive and failed to provide reliable incidence estimates in cohorts that included individuals with long-term infections. We evaluated >500,000 testing algorithms, that included the LAg-Avidity assay alone and MAAs with other biomarkers (BED capture immunoassay [BED-CEIA], BioRad-Avidity assay, HIV viral load, CD4 cell count), varying the assays and assay cutoffs. We identified an optimized 2-assay MAA that included the LAg-Avidity and BioRad-Avidity assays, and an optimized 4-assay MAA that included those assays, as well as HIV viral load and CD4 cell count. The two optimized MAAs classified all 845 samples from individuals infected >5 years as MAA negative and estimated incidence within a year of sample collection. These two MAAs produced incidence estimates that were consistent with those from longitudinal follow-up of cohorts. A comparison of the laboratory assay costs of the MAAs was also performed, and we found that the costs associated with the optimal two assay MAA were substantially less than with the four assay MAA., Conclusions: The LAg-Avidity assay did not perform well in a single-assay format, regardless of the assay cutoff. MAAs that include the LAg-Avidity and BioRad-Avidity assays, with or without viral load and CD4 cell count, provide accurate incidence estimates.

More than half a million Americans became newly infected with human immunodeficiency virus (HIV) in the first decade of the new millennium. The domestic epidemic has had the heaviest impact on men who have sex with men and persons from racial and ethnic minority populations, particularly black persons. For example, black men who have sex with men represent <1% of the US population but 25% of new HIV infections, according to Centers for Disease Control and Prevention estimates published in 2008. Although black and Hispanic women constitute 24% of all US women, they accounted for 82% of HIV infections among women in 2005, according to data from 33 states with confidential name-based reporting. There is a nearly 23-fold higher rate of AIDS diagnoses among black women (45.5 diagnoses per 100,000 women) and a nearly 6-fold higher rate among Hispanic women (11.2 diagnoses per 100,000 women), compared with the rate among white women (2.0 diagnoses per 100,000 women). Investigators from the HIV Prevention Trials Network, a National Institutes of Health-sponsored collaborative clinical trials group, have crafted a domestic research agenda with community input. Two new domestic studies are in progress (2009), and a community-based clinical trial feasibility effort is in development (2010 start date). These studies focus on outreach, testing, and treatment of infected persons as a backbone for prevention of HIV infection. Reaching persons not receiving health messages and services with novel approaches to both prevention and treatment is an essential priority for control of HIV infection in the United States; our research is designed to guide the best approaches and assess the impact of bridging treatment and prevention.

Objective: To determine the incidence of diabetes mellitus (DM) in a nationally representative cohort of HIV-infected women and a comparison group of HIV-uninfected women., Design: A prospective study between October 2000 and March 2006 of 2088 participants from the Women's Interagency HIV Study who did not have evidence of DM at enrollment (1524 HIV infected and 564 HIV uninfected)., Methods: Incident DM was defined as either having fasting glucose > or = 1.26 g/l, reporting antidiabetic medication, or reporting DM diagnosis (with subsequent confirmation by fasting glucose > or = 1.26 g/l or reported antidiabetic medication); all were assessed at semi-annual study visits., Results: DM developed in 116 HIV-infected and 36 HIV-uninfected women over 6802 person-years. HIV-infected women reporting no recent antiretroviral therapy had a DM incidence rate of 1.53/100 person-years; those reporting HAART containing a protease inhibitor (PI) had a rate of 2.50/100 person-years and those reporting non-PI-containing HAART a rate of 2.89/100 person-years. None of these rates differed from the HIV-uninfected women (1.96/100 person-years) substantially or beyond levels expected by chance. Among HIV-infected women, longer cumulative exposure to nucleoside reverse transcriptase inhibitors (NRTI) was associated with an increased risk of DM incidence compared with no NRTI exposure: relative hazard (RH) 1.81 [95% confidence interval (CI), 0.83-3.93] for > 0 to 3 years exposure and RH 2.64 (95% CI, 1.11-6.32) for > 3 years exposure., Conclusion: Longer cumulative exposure to NRTI was associated with increased DM incidence in HIV-infected women. Regular DM monitoring is advisable because NRTI form the backbone of effective antiretroviral therapy.

Objective: To estimate the incidence of lipoatrophy and lipohypertrophy among HIV-infected and HIV-uninfected women from the Women's Interagency HIV Study., Design: Eight hundred fifteen women with semiannual data on self-report of bidirectional change in body fat, anthropometric measurements, weight, and bioelectric impedance analysis were included in a 30-month incidence analysis., Methods: Lipoatrophy and lipohypertrophy in both peripheral (arms, legs, and buttocks) and central (waist, chest, and upper back) sites were defined by self-report of either a decrease or an increase in a body fat region over the previous 6 months that was confirmed by a corresponding change in anthropometric measurement., Results: Weight and total body fat increased in HIV-uninfected women but remained stable in HIV-infected women over 30 months. Among HIV-infected women, the incidence of peripheral (relative hazard, 2.1; 95% confidence interval [CI], 1.4-3.3) and central (relative hazard, 1.9; 95% CI, 1.2-2.8) lipoatrophy was about double that among HIV-uninfected women, after adjustment for age and race. The incidence of peripheral lipohypertrophy appeared lower among HIV-infected women than among HIV-uninfected women (relative hazard, 0.8; 95% CI, 0.6-1.1), while the incidence of central lipohypertrophy did not differ by HIV status. Of HIV-infected women with 2 of 4 lipodystrophy outcomes, most (81%) had combined peripheral and central lipoatrophy or combined peripheral and central lipohypertrophy. Only 14% of these women had both peripheral lipoatrophy and central lipohypertrophy., Conclusions: These prospective data suggest that lipoatrophy, affecting both peripheral and central sites, predominates in HIV-infected women. The simultaneous occurrence of peripheral lipoatrophy and central lipohypertrophy was uncommon.

Objective: To assess the association between protease inhibitor (PI) use and the incidence of diabetes mellitus (DM) among participants in the Women's Interagency HIV Study., Design: Prospective multicenter cohort study. The diagnosis of DM was based on self-report at semiannual interviews conducted from 1994 to 1998., Setting: Six inner-city clinical sites in the United States (Brooklyn, NY; Bronx, NY; Washington, DC; Chicago, IL; San Francisco, CA; and Los Angeles, CA)., Participants: A total of 1785 nonpregnant women who had no history of prior DM. The women made up four groups: 1) PI users (n = 609, person-years [PY] at risk = 707); 2) reverse transcriptase inhibitor (RTI)-only users (n = 932, PY = 1486); 3) HIV-infected women reporting no antiretroviral therapy (ART) ever (n = 816, PY = 1480); and 4) HIV-uninfected women (n = 350, PY = 905)., Main Outcomes: Incidence of DM and median body mass index (BMI) from 1995 to 1998 were compared among the four groups., Results: Sixty-nine incident cases of DM occurred among 1785 women (1.5 cases per 100 PY; 95% CI: 1.2-1.9). The incidence of DM among PI users was 2.8 cases per 100 PY (2.8%) versus 1.2% among both RTI users and women on no ART (95% CI: 1.6-4.1 [PI]; 0.7-1.8 [RTI and no ART]; P = 0.01 for comparison of the PI group with the RTI group) and 1.4% among HIV-uninfected women (95% CI: 0.7-2.2, P = 0.06 for comparison with PI group). Weight gain was not associated with either PI or RTI use. Multivariate models identified PI use (hazard ratio [HR] = 2.90 [95% CI: 1.50-5.60]; P = 0.002), age (HR = 1.75 per 10 years [95% CI: 1.31-2.34]; P = 0.0002) and BMI as independent risk factors for DM., Conclusions: PI use was associated with a threefold increase in the risk of reporting incident DM. Routine screening for diabetes, particularly among older and heavier patients using PI therapy, is advisable.