Majority Of HIV-1 Research Articles

Combination Antiretroviral Therapy in African Nursing Mothers and Drug Exposure in Their Infants: New Pharmacokinetic and Virologic Findings

Africa’s HIV/AIDS epidemic has reached crisis proportions and calls for a rapid expansion of both prevention and treatment services particularly among young women and children. Mother-to-child transmission (MTCT) is the most important source of HIV-1 infection in children and prolonged breast-feeding is associated with a near doubling of the risk of MTCT. In resource-limited settings the majority of HIV-1–infected mothers choose to breast-feed because of cultural norms the high cost of formula the lack of a safe water supply and the stigma associated with not breast-feeding. Reducing HIV-1 transmission during lactation remains a pressing global health dilemma confronting HIV-1–infected women health-care providers and policy makers. Clinical trials are currently under way to assess whether the use of highly active antiretroviral therapy (HAART) during late pregnancy and during the first 6 months of lactation followed by early weaning can substantially reduce the risk of HIV-1 transmission among breast-feeding women. In addition it is anticipated that eligible HIV-1–infected nursing mothers in sub- Saharan Africa will increasingly be able to receive HAART for the maintenance of their own health. (excerpt)

Apparent founder effect during the early years of the San Francisco HIV type 1 epidemic (1978-1979).

HIV-1 envelope sequence variants were RT-PCR amplified from serum samples cryopreserved in San Francisco in 1978-1979. The HIV-1 subtype B env V3-V5 sequences from four homosexual men clustered phylogenetically, with a median nucleotide distance of 2.8%, reflecting a recent common origin. These early U.S. HIV-1 env variants mapped close to the phylogenetic root of the subtype B tree while env variants collected in the United States throughout the 1980s and 1990s showed, on average, increasing genetic diversity and divergence from the subtype B consensus sequence. These results indicate that the majority of HIV-1 currently circulating in the United States may be descended from an initial introduction and rapid spread during the mid- to late 1970s of subtype B viruses with limited variability (i.e., a founder effect). As expected from the starburst-shaped phylogeny of HIV-1 subtype B, contemporary U.S. strains were, on average, more closely related at the nucleic acid and amino acid levels to the earlier 1978-1979 env variants than to each other. The growing levels of HIV-1 genetic diversity, one of multiple obstacles in designing a protective vaccine, may therefore be mitigated by using epidemic founding variants as antigenic strains for protection against contemporary strains.

The neutralization relationship of HIV type 1, HIV type 2, and SIVcpz is reflected in the genetic diversity that distinguishes them.

Neutralizing antibody (NA) patterns in the sera of individuals naturally infected with human immunodeficiency virus (HIV) type 1, HIV-2, and the simian immunodeficiency virus (SIVcpz) to their homologous and heterologous isolates were determined in a peripheral blood mononuclear cell-based neutralization assay. We examined the role of the V3 loop of HIV-1 and SIVcpz in neutralization and the cross-reactivities among them. Cross-neutralization by sera of humans and chimpanzees naturally infected, respectively, with HIV-1 and SIVcpz isolates was more extensive than the infrequent and low-titer cross-neutralizations observed between HIV-1 and HIV-2. Neutralization of 9 of the 16 HIV-1 isolates by 9 of 10 HIV-2 and all 3 SIVcpz antibody-positive sera were weak and sporadic (titer, 1:10-1:160). Twelve of 15 HIV-1 sera neutralized the 2 SIVcpz isolates with titers of 1:10-1:320 but only sporadically neutralized the 6 HIV-2 isolates (titers: 1:10-1:20). The majority of HIV-1 and SIVcpz sera bound to the V3 peptides although their binding capacity did not readily reflect their neutralizing capacity. The HIV-2 sera did not or only weakly bound to the V3 peptides. These results suggest that HIV-1 and SIVcpz share some structural and functional similarities that set them apart from HIV-2.