Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5′ and 3′ half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3–6 days before symptom onset and 14–17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized.

Context More than 350 communities in the United States have committed to ending chronic homelessness. One nationally prominent approach, Housing First, offers early access to permanent housing without requiring completion of treatment or, for clients with addiction, proof of sobriety. Methods This article reviews studies of Housing First and more traditional rehabilitative (e.g., “linear”) recovery interventions, focusing on the outcomes obtained by both approaches for homeless individuals with addictive disorders. Findings According to reviews of comparative trials and case series reports, Housing First reports document excellent housing retention, despite the limited amount of data pertaining to homeless clients with active and severe addiction. Several linear programs cite reductions in addiction severity but have shortcomings in long-term housing success and retention. Conclusions This article suggests that the current research data are not sufficient to identify an optimal housing and rehabilitation approach for an important homeless subgroup. The research regarding Housing First and linear approaches can be strengthened in several ways, and policymakers should be cautious about generalizing the results of available Housing First studies to persons with active addiction when they enter housing programs.

Recent studies indicate that sexual transmission of human immunodeficiency virus type 1 (HIV-1) generally results from productive infection by only one virus, a finding attributable to the mucosal barrier. Surprisingly, a recent study of injection drug users (IDUs) from St. Petersburg, Russia, also found most subjects to be acutely infected by a single virus. Here, we show by single-genome amplification and sequencing in a different IDU cohort that 60% of IDU subjects were infected by more than one virus, including one subject who was acutely infected by at least 16 viruses. Multivariant transmission was more common in IDUs than in heterosexuals (60% versus 19%; odds ratio, 6.14; 95% confidence interval [CI], 1.37 to 31.27; P ‫؍‬ 0.008). These findings highlight the diversity in HIV-1 infection risks among different IDU cohorts and the challenges faced by vaccines in protecting against this mode of infection.Elucidation of virus-host interactions during and immediately following the transmission event is one of the great challenges and opportunities in human immunodeficiency virus (HIV)/AIDS prevention research (14-16, 31, 34, 45). Recent innovations involving single-genome amplification (SGA), direct amplicon sequencing, and phylogenetic inference based on a model of random virus evolution (18)(19)(20)43) have allowed for the identification of transmitted/founder viruses that actually cross from donor to recipient, leading to productive HIV type 1 (HIV-1) infection. Our laboratory and others have made the surprising finding that HIV-1 transmission results from productive infection by a single transmitted/founder virus (or virally infected cell) in ϳ80% of HIV-infected heterosexuals and in ϳ60% of HIV-infected men who have sex with men (MSM) (1,13,18,24). These studies thus provided a precise quantitative estimate for the long-recognized genetic bottleneck in HIV-1 transmission (6, 11-13, 17, 25, 28, 30, 35, 38, 42, 47-49) and a plausible explanation for the low acquisition rate per coital act and for graded infection risks associated with different exposure routes and behaviors (15,36).In contrast to sexual transmission of HIV-1, virus transmission resulting from injection drug use has received relatively little attention (2, 3, 29, 42) despite the fact that injection drug use-associated transmission accounts for as many as 10% of new infections globally (26, 46). We hypothesized that SGA strategies developed for identifying transmitted/founder viruses following mucosal acquisition are applicable to deciphering transmission events following intravenous inoculation and that, due to the absence of a mucosal barrier, injection drug users (IDUs) exhibit a higher frequency of multiple-variant transmission and a wider range in numbers of transmitted viruses than do acutely infected heterosexual subjects. We obtained evidence in support of these hypotheses from the simian immunodeficiency virus (SIV)-Indian rhesus macaque infection model, where we showed that discrete low-diversity viral lineages emanating from singl...

Background Racial/ethnic health care disparities are well described in people living with HIV/AIDS, although the processes underlying observed disparities are not well elucidated. Methods A retrospective analysis nested in the UAB 1917 Clinic Cohort observational HIV study evaluated patients between August 2004 and January 2007. Factors associated with appointment non-adherence, a proportion of missed outpatient visits, were evaluated. Next, the role of appointment non-adherence in explaining the relationship between African American race and virologic failure (plasma HIV RNA >50 copies/mL) was examined using a staged multivariable modeling approach. Results Among 1,221 participants a broad distribution of appointment non-adherence was observed, with 40% of patients missing at least 1 in every 4 scheduled visits. The adjusted odds of appointment non-adherence were 1.85 times higher in African American patients compared to Whites (95%CI=1.61–2.14). Appointment non-adherence was associated with virologic failure (OR 1.78; 95%CI=1.48–2.13), and partially mediated the relationship between African American race and virologic failure. African Americans had 1.56 times the adjusted odds of virologic failure (95%CI=1.19–2.05), which declined to 1.30 (95%CI=0.98–1.72) when controlling for appointment non-adherence, a hypothesized mediator. Conclusions Appointment non-adherence was more common in African American patients, associated with virologic failure, and appeared to explain part of observed racial disparities in virologic failure.