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Objective: We employed a high-dimensional covariate adjustment method in microbiome analysis to better control for behavioural and clinical confounders, and in doing so examine the effects of HIV on the rectal microbiome., Design: Three hundred and eighty-three MSM were grouped into four HIV viremia categories: HIV negative (n = 200), HIV-positive undetectable (HIV RNA < 20 copies/ml; n = 66), HIV-positive suppressed (RNA 20-200 copies/ml; n = 72) and HIV-positive viremic (RNA > 200 copies/ml; n = 45)., Methods: We performed 16S rRNA gene sequencing on rectal swab samples and used inverse probability of treatment-weighted marginal structural models to examine differences in microbial composition by HIV viremia category., Results: HIV viremia explained a significant amount of variability in microbial composition in both unadjusted and covariate-adjusted analyses (R = 0.011, P = 0.02). Alterations in bacterial taxa were more apparent with increasing viremia. Relative to the HIV-negative group, HIV-positive undetectable participants showed depletions in Brachyspira, Campylobacter and Parasutterella, while suppressed participants demonstrated depletions in Barnesiella, Brachyspira and Helicobacter. The microbial signature of viremic men was most distinct, showing enrichment in inflammatory genera Peptoniphilus, Porphyromonas and Prevotella and depletion of Bacteroides, Brachyspira and Faecalibacterium, among others., Conclusion: Our study shows that, after accounting for the influence of multiple confounding factors, HIV is associated with dysbiosis in the gastrointestinal microbiome in a dose-dependent manner. This analytic approach may allow for better identification of true microbial associations by limiting the effects of confounding, and thus improve comparability across future studies.

Objective: To evaluate adjustment procedures that have been proposed to correct HIV incidence rates derived from cross-sectional surveys of biomarkers (e.g. BED capture enzyme immunoassay). These procedures were motivated by some reports that the biomarker BED approach overestimates incidence when compared to cohort studies., Design: Consideration of the Hargrove and McDougal adjustment procedures that adjust biomarker estimates of HIV incidence rates for misclassification with respect to the timing of infections., Methods: : Performed mathematical and statistical analysis of the adjustment formulas. Evaluated sources of error in cohort studies of incidence that could also explain discrepancies between cohort and biomarker estimates., Results: The McDougal adjustment has no net effect on the estimate of HIV incidence because false positives exactly counterbalance false negatives. The Hargrove adjustment has a mathematical error that can cause significant underestimation of HIV incidence rates, especially if there is a large pool of prevalent long-standing infections., Conclusion: The two adjustment procedures of biomarker incidence estimates evaluated here that purport to correct for misclassification do not increase accuracy and in some situations can introduce significant bias. Instead, the accuracy of biomarker estimates can be increased through improvements in the estimates of the mean window period of the populations under study and the representativeness of the cross-sectional samples. Cohort estimates of incidence are also subject to important sources of error and should not blindly be considered the gold standard for assessing the validity of biomarker estimates.

Objective: To develop a pooling method for detection of viral RNA for diagnosis of acute HIV infection and estimation of HIV-1 incidence., Methods: Sera from 700 consecutive seronegative patients attending sexually transmitted disease clinics in Pune, India, were screened individually for p24 antigen, and pooled into seven pools of 100 for detection of HIV-1 RNA by reverse transcriptase-polymerase chain reaction. HIV-1 incidence was calculated by the traditional cohort method, the p24 antigen method, and a multistage pooling method in which RNA-positive pools were re-analyzed in smaller pools., Results: Sera from 700 individuals were grouped into seven pools of 100, of which four were positive. These four positive pools were subdivided into eight pools of 50, of which seven were positive. The seven positive pools were subdivided into 35 pools of 10, of which 10 were positive. Based on the 10 RNA-positive pools, the point estimate of HIV-1 incidence was 19.9% per year [95% confidence interval (CI), 7.3-31.8%]. Of the 700 samples analyzed for p24 antigen, eight were positive, resulting in a point estimate of incidence of 18.5%/year (8.0-36.5%). In contrast, the incidence rate based on the traditional cohort method of follow-up was lower at 9.4%/year (4.8-16.4%) due to a low follow-up rate. Testing of individual samples from the 10 RNA-positive pools identified 10 individuals with acute primary HIV-1., Conclusion: The multistage pooling method for detection of HIV-1 RNA was more sensitive than the p24 antigen method, and was five-fold less expensive than the p24 antigen assays. Pooling samples for RNA detection was effective in estimating current incidence rates with cost savings that would be practical for use in developing countries.

Objective: To describe the design and first-round survey results of a trial of intensive sexually transmitted disease (STD) control to reduce HIV-1 incidence., Study Design: Randomized, controlled, community-based trial in Rakai District, Uganda., Methods: In this ongoing study, 56 communities were grouped into 10 clusters designed to encompass social/sexual networks; clusters within blocks were randomly assigned to the intervention or control arm. Every 10 months, all consenting resident adults aged 15-59 years are visited in the home for interview and sample collection (serological sample, urine, and, in the case of women, self-administered vaginal swabs). Sera are tested for HIV-1, syphilis, gonorrhea, chlamydia, trichomonas and bacterial vaginosis. Following interview, all consenting adults are offered directly observed, single oral dose treatment (STD treatment in the intervention arm, anthelminthic and iron-folate in the control arm). Treatment is administered irrespective of symptoms or laboratory testing (mass treatment strategy). Both arms receive identical health education, condom and serological counseling services., Results: In the first home visit round, the study enrolled 5834 intervention and 5784 control arm subjects. Compliance with interview, sample collection and treatment was high in both arms (over 90%). Study arm populations were comparable with respect to sociodemographic and behavioral characteristics, and baseline HIV and STD rates. The latter were high: 16.9% of all subjects were HIV-positive, 10.0% had syphilis, and 23.8% of women had trichomonas and 50.9% had bacterial vaginosis., Conclusions: Testing the effects of STD control on AIDS prevention is feasible in this Ugandan setting.

During a prospective study of the natural history of AIDS, 1001 homosexual or bisexual men were offered the opportunity to learn their HIV antibody status. Six hundred and seventy (67%) of the population who elected to do so were similar to the 331 (33%) people who declined in a number of baseline characteristics. All were counselled to practice safe sex. To determine whether disclosure of HIV serologic status affects subsequent sexual behavior, we examined changes at four time-points in three sexual activities during the previous 6 months: the number of male partners with whom the participant had (1) sexual intercourse, (2) unprotected anal receptive intercourse, and (3) unprotected anal insertive intercourse. All activities decreased strikingly over the 18-month study period. Following disclosure, the mean number of partners dropped to 47% of the baseline number in people remaining unaware of their antibody status, to 45% in people told that they were seropositive, and to 55% in people told that they were seronegative. The mean number of partners for younger seropositives declined less than that for older seropositives. The mean number of partners with whom unprotected anal receptive intercourse was practiced declined to 57% of baseline in unaware people, 42% in aware seropositives, and 62% in aware seronegatives. The mean number of partners with whom unprotected anal insertive intercourse was practiced declined to 52% of baseline in unaware people, 42% in aware seropositives and 59% in aware seronegatives. Disclosure of a negative test result led to a significantly smaller decline in these sexual activities.(ABSTRACT TRUNCATED AT 250 WORDS)