Recent observations on HIV type-1 infection in the genital tract of men and women

Coombs, Robert W.; Reichelderfer, Patricia; Landay, Alan

doi:10.1097/00002030-200303070-00001

Cited by 212 publications

(190 citation statements)

References 227 publications

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“…The higher susceptibility of women to sexually transmitted infections (STIs) including HIV has been attributed to the African patriarchal norms of men dominating family decision-making and biological vulnerability of women (Magadi, 2011;Ackerman & de Klerk, 2002;Coombs et al, 2003;Phyllis, 2013). Given the tempo of the HIV/AIDS epidemic in South Africa, understanding the extent social values influence the vulnerability of women to HIV infection in marital relationships carries some sense of urgency.…”

Section: Literature Reviewmentioning

confidence: 99%

Attitude towards sexual control among women in conjugal union in the era of the HIV/AIDS epidemic in Mahikeng, South Africa

Osuafor

Mturi

2014

APS

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Section: Literature Reviewmentioning

confidence: 99%

Attitude towards sexual control among women in conjugal union in the era of the HIV/AIDS epidemic in Mahikeng, South Africa

Osuafor

Mturi

2014

APS

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“…Virus replicating within the male genital tract could therefore develop distinct, compartment-specific characteristics in response to these local selective pressures (10,16,17,20,21,32,41,50,53). Although genetic differences between blood-and semen-derived HIV in an individual have been documented, a seminal signature sequence remains elusive (6,10). This failure to identify a signature sequence could be attributable to the fact that previous efforts mainly focused on proviral DNA sequences, which often represent archival viral genotypes rather than contemporary, actively replicating variants (4,44).…”

Section: Most Human Immunodeficiency Virus (Hiv) Transmissionmentioning

confidence: 99%

Semen-Specific Genetic Characteristics of Human Immunodeficiency Virus Type 1 env

Pillai

Good

Pond

et al. 2005

J Virol

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Human immunodeficiency virus type 1 (HIV-1) in the male genital tract may comprise virus produced locally in addition to virus transported from the circulation. Virus produced in the male genital tract may be genetically distinct, due to tissue-specific cellular characteristics and immunological pressures. HIV-1 env sequences derived from paired blood and semen samples from the Los Alamos HIV Sequence Database were analyzed to ascertain a male genital tract-specific viral signature. Machine learning algorithms could predict seminal tropism based on env sequences with accuracies exceeding 90%, suggesting that a strong genetic signature does exist for virus replicating in the male genital tract. Additionally, semen-derived viral populations exhibited constrained diversity (P < 0.05), decreased levels of positive selection (P < 0.025), decreased CXCR4 coreceptor utilization, and altered glycosylation patterns. Our analysis suggests that the male genital tract represents a distinct selective environment that contributes to the apparent genetic bottlenecks associated with the sexual transmission of HIV-1.Most human immunodeficiency virus (HIV) transmission events globally occur via mucosal exposure to male genital secretions carrying the virus (34,46). Although the risk of sexual HIV transmission correlates with the amount of virus present in the blood of the source partner (36), the correlation between the viral load in the blood and genital compartment is inconsistent (3,23,24). The biological determinants that influence the transmissibility of different viral variants from within the genital tract of the HIV-infected source are still incompletely understood. Since transmitted virus represents the initial virus that the immune system encounters, the understanding of its composition will be critical in our attempts to develop a successful HIV vaccine (1,7,54).HIV in each chronically infected person exists as a diverse population of related genetic variants (5,12,20). Anatomic compartmentalization of these variants has been described in blood, lung, central nervous system, and genital tract (10,16,17,20,21,32,41,50,53). Male genital tract tissues (e.g., the prostate, seminal vesicles, and epididymis) serve as sites of viral replication and are likely to differ from peripheral tissues in immunological surveillance, target cell characteristics, and efficiencies of drug penetration (10,17,43). Virus replicating within the male genital tract could therefore develop distinct, compartment-specific characteristics in response to these local selective pressures (10,16,17,20,21,32,41,50,53). Although genetic differences between blood-and semen-derived HIV in an individual have been documented, a seminal signature sequence remains elusive (6, 10). This failure to identify a signature sequence could be attributable to the fact that previous efforts mainly focused on proviral DNA sequences, which often represent archival viral genotypes rather than contemporary, actively replicating variants (4, 44).We investigated viral genetic...

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“…35,36 Sexual transmission of HIV has been closely linked to viral load in the blood of the infected host, [37][38][39][40][41] which probably serves as a surrogate, albeit imperfect, for HIV concentration in the genital tract. 42,43 In addition to lowering plasma viral load to nearly undetectable levels, ART can decrease viral load in genital secretions, 44,45 although patients having a detectable semen HIV load may have no detectable virus in their blood plasma, highlighting the residual risk of HIV-1 transmission during unprotected intercourse. 46 Observational studies and recent modeling work have triggered considerable interest and concerns regarding the use of ART in HIV-infected individuals to prevent secondary transmission.…”

Section: Introductionmentioning

confidence: 99%

AIDS Vaccines and Preexposure Prophylaxis: Is Synergy Possible?

Excler

Rida²,

Priddy

et al. 2011

AIDS Research and Human Retroviruses

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While the long-term goal is to develop highly effective AIDS vaccines, first generation vaccines may be only partially effective. Other HIV prevention modalities such as preexposure prophylaxis with antiretrovirals (PrEP) may have limited efficacy as well. The combined administration of vaccine and PrEP (VAXPREP), however, may have a synergistic effect leading to an overall benefit that is greater than the sum of the individual effects. We propose two test-of-concept trial designs for an AIDS vaccine plus oral or topical ARV. In one design, evidence that PrEP reduces the risk of HIV acquisition is assumed to justify offering it to all participants. A two-arm study comparing PrEP alone to VAXPREP is proposed in which 30 to 60 incident infections are observed to assess the additional benefit of vaccination on risk of infection and setpoint viral load. The demonstrated superiority of VAXPREP does not imply vaccine alone is efficacious. Similarly, the lack of superiority does not imply vaccine alone is ineffective, as antagonism could exist between vaccine and PrEP. In the other design, PrEP is assumed not to be in general use. A 2Â2 factorial design is proposed in which high-risk individuals are randomized to one of four arms: placebo vaccine given with placebo PrEP, placebo vaccine given with PrEP, vaccine given with placebo PrEP, or VAXPREP. Between 60 and 210 infections are required to detect a benefit of vaccination with or without PrEP on risk of HIV acquisition or setpoint viral load, with fewer infections needed when synergy is present.

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Recent observations on HIV type-1 infection in the genital tract of men and women

Cited by 212 publications

References 227 publications

Attitude towards sexual control among women in conjugal union in the era of the HIV/AIDS epidemic in Mahikeng, South Africa

Attitude towards sexual control among women in conjugal union in the era of the HIV/AIDS epidemic in Mahikeng, South Africa

Semen-Specific Genetic Characteristics of Human Immunodeficiency Virus Type 1 env

AIDS Vaccines and Preexposure Prophylaxis: Is Synergy Possible?

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