HIV-2 integrase variation in integrase inhibitor-naïve adults in Senegal, West Africa.

Background: Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance.

Viral linkage in HIV-1 seroconverters and their partners in an HIV-1 prevention clinical trial.

Background: Characterization of viruses in HIV-1 transmission pairs will help identify biological determinants of infectiousness and evaluate candidate interventions to reduce transmission. Although HIV-1 sequencing is frequently used to substantiate linkage between newly HIV-1 infected individuals and their sexual partners in epidemiologic and forensic studies, viral sequencing is seldom applied in HIV-1 prevention trials. The Partners in Prevention HSV/HIV Transmission Study (ClinicalTrials.

Mutation of HIV-1 genomes in a clinical population treated with the mutagenic nucleoside KP1461.

The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class of antiretroviral drugs designed to increase viral mutation rates, with the goal of eventually causing the collapse of the viral population. Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first "mechanism validation" phase II clinical trial of a mutagenic base analog in which individuals previously treated with antiviral drugs received 1600 mg of KP1461 twice per day for 124 days. Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study, however, the mutation spectrum of HIV was altered.

Multistage genomewide association study identifies a locus at 1q41 associated with rate of HIV-1 disease progression to clinical AIDS.

Background: A mean of 9-10 years of human immunodeficiency virus type 1 (HIV-1) infection elapse before clinical AIDS develops in untreated persons, but this rate of disease progression varies substantially among individuals. To investigate host genetic determinants of the rate of progression to clinical AIDS, we performed a multistage genomewide association study.

Methods: The discovery stage comprised 156 individuals from the Multicenter AIDS Cohort Study, enriched with rapid and long-term nonprogressors to increase statistical power.

HIV-1 superinfection in the antiretroviral therapy era: are seroconcordant sexual partners at risk?

Background: Acquisition of more than one strain of human immunodeficiency virus type 1 (HIV-1) has been reported to occur both during and after primary infection, but the risks and repercussions of dual and superinfection are incompletely understood. In this study, we evaluated a longitudinal cohort of chronically HIV-infected men who were sexual partners to determine if individuals acquired their partners' viral strains.

Methodology: Our cohort of HIV-positive men consisted of 8 couples that identified themselves as long-term sexual partners.

Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa.

Background: The efficacy of various antiretroviral (ARV) therapy regimens for human immunodeficiency virus type 2 (HIV-2) infection remains unclear. HIV-2 is intrinsically resistant to the nonnucleoside reverse-transcriptase inhibitors and to enfuvirtide and may also be less susceptible than HIV-1 to some protease inhibitors (PIs). However, the mutations in HIV-2 that confer ARV resistance are not well characterized.

HIV type 2 protease, reverse transcriptase, and envelope viral variation in the PBMC and genital tract of ARV-naive women in Senegal.

Unique viral variants and resistance mutations may occur in the genital tract of HIV-2 ARV-naive infected women. We sequenced and phylogenetically analyzed protease (PR), reverse transcriptase (RT), and envelope (ENV) from PBMC and genital tract samples from four ARV-naive women in Senegal. HIV-2 protease polymorphisms that predict HIV-1 protease inhibitor (PI) resistance were common.

HIV-1 variation before seroconversion in men who have sex with men: analysis of acute/early HIV infection in the multicenter AIDS cohort study.

Understanding the characteristics of human immunodeficiency virus (HIV) necessary for infection in a new host is a critical goal for acquired immunodeficiency syndrome (AIDS) research. We studied the characteristics of HIV-1 envelope genes in 38 men in the Multicenter AIDS Cohort Study cohort before seroconversion. We found a range of diversity (0.

HIV type 1 superinfection with a dual-tropic virus and rapid progression to AIDS: a case report.

Background: The occurrence of human immunodeficiency virus type 1 (HIV-1) superinfection has implications for vaccine development and our understanding of HIV pathogenesis and transmission.

Methods And Results: We describe a subject from the Multicenter AIDS Cohort Study who was superinfected with a dual-tropic (CXCR4/CCR5-utilizing) HIV-1 subtype B strain between 0.8 and 1.

Dual HIV-1 infection associated with rapid disease progression.

Infection with two strains of HIV-1 has implications for understanding HIV transmission and vaccine development; however, frequency and pathogenic consequences of dual infection are unknown. We assessed 64 patients for dual infection with heteroduplex mobility assay, viral sequencing, and phylogenetic methods. HIV disease outcomes were available in 34 patients.