Participation in research involving novel sampling and study designs to identify acute HIV-1 infection among minority men who have sex with men.

HIV-1 infection disproportionally affects African-American and Latino men who have sex with men (MSM). Their inclusion in biomedical and behavioral research is critical to understanding and addressing HIV vulnerability. Using focus groups, we sought to understand the perceptions related to participating in biomedical research of acute/recent HIV-1 infection (AHI) using complex sampling and data collection methods to reach this hidden group at highest risk of acquiring and transmitting HIV. Given the potential impact of AHI on HIV transmission in MSM, it is important to understand this intersection for HIV prevention, care, and treatment purposes. The aim of this study was to understand how recruitment and data collection methods affect AHI research participation willingness particularly among MSM of color. Findings suggest that major barriers to research participation with complex sampling to identify AHI and intensive risk behavior collection such as diary methods are lack of anonymity, partner disclosure, and study fatigue. The authors explore implications for future study designs and development based on these findings.

Antiretroviral-drug resistance among patients recently infected with HIV.

BACKGROUND: Among persons in North America who are newly infected with the human immunodeficiency virus (HIV), the prevalence of transmitted resistance to antiretroviral drugs has been estimated at 1 to 11 percent. METHODS: We performed a retrospective analysis of susceptibility to antiretroviral drugs before treatment and drug-resistance mutations in HIV in plasma samples from 377 subjects with primary HIV infection who had not yet received treatment and who were identified between May 1995 and June 2000 in 10 North American cities. Responses to treatment could be evaluated in 202 subjects. RESULTS: Over the five-year period, the frequency of transmitted drug resistance increased significantly. The frequency of high-level resistance to one or more drugs (indicated by a value of more than 10 for the ratio of the 50 percent inhibitory concentration [IC50] for the subject's virus to the IC50 for a drug-sensitive reference virus) increased from 3.4 percent during the period from 1995 to 1998 to 12.4 percent during the period from 1999 to 2000 (P=0.002), and the frequency of multidrug resistance increased from 1.1 percent to 6.2 percent (P=0.01). The frequency of resistance mutations detected by sequence analysis increased from 8.0 percent to 22.7 percent (P<0.001), and the frequency of multidrug resistance detected by sequence analysis increased from 3.8 percent to 10.2 percent (P=0.05). Among subjects infected with drug-resistant virus, the time to viral suppression after the initiation of antiretroviral therapy was longer (P=0.05), and the time to virologic failure was shorter (P=0.05). CONCLUSIONS: The proportion of new HIV infections that involve drug-resistant virus is increasing in North America. Initial antiretroviral therapy is more likely to fail in patients who are infected with drug-resistant virus. Testing for resistance to drugs before therapy begins is now indicated even for recently infected patients.

Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins.

Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge.

Compartmentalization of surface envelope glycoprotein of human immunodeficiency virus type 1 during acute and chronic infection.

Human immunodeficiency virus type 1 is characterized by extensive genetic heterogeneity. Having previously demonstrated that, in the peripheral blood, the initial viral population is more homogeneous than at subsequent stages of infection, we have extended our studies to tissue samples, allowing comparisons between viral populations in peripheral blood and tissues during both the acute and chronic stages of infection. We found that homogeneity in gp120 sequences during the acute infection phase is not just restricted to the peripheral blood but also extends to other tissue compartments. However, in chronically infected individuals, heterogeneous and distinct viral populations were found in different compartments. We therefore conclude that the dominant and homogeneous viral population observed during the acute infection phase is likely to infiltrate lymphoid tissues and form the genetic bases for subsequent diversification. It is therefore likely that the compartmentalization of viral sequences observed in chronically infected patients reflects a gradual diversification of a common dominant viral variant rather than the preferential migration of distinct viral populations to different tissue compartments at the beginning of infection.