Human immunodeficiency virus type 1 shedding pattern in semen correlates with the compartmentalization of viral Quasi species between blood and semen.
ABSTRACT High levels of human immunodeficiency virus (HIV) type 1 have been detected in semen at all stages of disease. However, it is not clear whether HIV-1 is shed in semen continuously or intermittently. In a prospective longitudinal study, viral RNA was measured weekly for 10 weeks in semen and blood of HIV-seropositive subjects. Results showed three different patterns of HIV-1 shedding in semen: none (28%), continuous (28%), and intermittent (44%). In contrast, there was no change in blood plasma virus load during the study period. Phylogenetic analysis of the envelope sequences of HIV-1 RNA in semen and blood revealed distinct virus populations in semen and blood of intermittent shedders but similar virus populations in the semen and blood of continuous shedder. These results indicate for the first time that HIV-1 is shed primarily in an intermittent manner and that shedding patterns of HIV-1 in semen are related to compartmentalization of HIV-1 between semen and blood.
SourceAvailable from: Kathryn Anastos[Show abstract] [Hide abstract]
ABSTRACT: Background: Evolution of HIV-1 drug resistance in the female genital tract is relevant not only to antiretroviral treatment (ART), but also to prevention of heterosexual and mother-to-child transmission (MTCT). Although ART can reduce MTCT rates, drug resistance may emerge, particularly in women treated with nevirapine (NVP). Methods: We compared HIV-1 genotypic resistance mutations in contemporaneous plasma and cervicovaginal lavage (CVL) from 20 non-pregnant, US women receiving ART. For 16 women, we sequenced pol genes (protease and RT, ~1600 bp) obtained by endpoint dilution PCR or cloning. In 4, we obtained consensus sequences of RT genes. 373 unique pol sequences were analyzed. One woman was studied at 4 serial timepoints, 2 before and 2 after initiating NVP; both gp120 env and pol genes were studied. Results: 50% of patients displayed high-level genotypic resistance to ART, and in each case, HIV-1 from CVL and plasma was resistant to the same drugs. In particular, 4 of 5 NVP-treated women harbored NVP-resistant strains in both sites. The woman who was studied serially demonstrated NVP resistance in both CVL and plasma soon after treatment began, but mutations differed in each compartment; K103N predominated in plasma and G190S in CVL. Six months later, the K103N mutation predominated in both sites. Phylogenetic analyses of sequences obtained during NVP treatment showed a high level of diversity and multiple intrapatient recombinants, with recombination breakpoints within the env region. Conclusion: 50% of women exhibited high-level genotypic HIV-1 drug resistance, with CVL and plasma harboring virus resistant to a very similar spectrum of drugs. One woman studied serially displayed a different pattern of evolution of resistance in CVL vs plasma and also showed evidence of multiple intrapatient HIV-1 recombinants involving the gp120 gene.Infectious Diseases Society of America 2004 Annual Meeting; 10/2004
[Show abstract] [Hide abstract]
ABSTRACT: Although semen is the principal vector of human immunodeficiency virus (HIV) dissemination worldwide, the origin of the infected leukocytes and free viral particles in this body fluid remain elusive. Here we review the accumulated evidence of the genital origin of HIV in semen from therapy naive individuals and men receiving suppressive highly active antiretroviral therapy (HAART), summarize the data on the detection and localization of HIV/SIV within the male genital tract, discuss the potential involvement of each genital tissue as a source of infected cells and virions in semen in the absence and presence of HAART, and suggest further studies. Deci-phering the exact sources of HIV in semen will be crucial to improving HIV transmission prevention strategies. Semen is composed of cells and secretions arising from the male genital tract (MGT), which encompasses sev-eral exocrine organs and ducts (Figure 1). Although semen represents the major vehicle of human immuno-deficiency virus (HIV) transmission, the origins of infected leukocytes and virions in this body fluid re-main unclear. HIV contaminates semen during the acute, chronic, and AIDS stages of infection. Impor-tantly, HIV shedding persists in the semen of a subset of individuals receiving suppressive highly active antire-troviral therapy (HAART), indicating that the male genital tract may constitute a viral reservoir. Here we re-view evidence of a local origin of HIV in semen based on (1) the phylogenetic comparisons of HIV and simian immunodeficiency virus (SIV) strains in semen and blood; (2) the findings of HIV persistence in the semen of men receiving suppressive HAART; and (3) the detection/localization of HIV/SIV within MGT tis-sues. The potential contribution of each MGT tissue to semen contamination by HIV is finally discussed.
[Show abstract] [Hide abstract]
ABSTRACT: There is increasing evidence that male or female genital tract represent a distinct replication compartment for human immunodeficiency virus type 1 (HIV-1) and that such compartments may serve as a virus reservoir. Forty-four paired plasma and vaginal samples from HIV-infected females undergoing HAART were collected to examine the viral responses to antiretroviral therapy and to assess the possible role of the vaginal tract as a reservoir for drug-resistant variants. Twenty-one females had detectable viral RNA both in plasma and vaginal fluid, whereas 14 females had detectable virus only in plasma. Twelve paired samples were used to analyze HIV-1 pol sequences for the presence of drug resistance-associated mutations. Nine of the twelve paired samples exhibited discordant drug resistance mutation patterns. The other three females showed identical drug resistance-associated mutations. However, further examination of protease and RT showed numerous non-drug-associated mutations that corresponded to predefined CTL epitopes. These non-drug-associated mutations were different between plasma and vaginal viruses, suggesting that evolution of HIV-1 was independent in these two compartments.Virology 05/2004; DOI:10.1016/S0042-6822(04)00261-2 · 3.28 Impact Factor