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The importance of semen leukocytes in HIV-1 transmission and the development of prevention strategies.

ABSTRACT: HIV-1 sexual transmission occurs mostly through contaminated semen, which is a complex mixture of soluble factors with immunoregulatory functions and cells. It is well established that semen cells from HIV-1-infected men are able to produce the virus and that are harnessed to efficiently interact with mucosal barriers exposed during sexual intercourse. Several cofactors contribute to semen infectivity and may enhance the risk of HIV-1 transmission to a partner by increasing local HIV-1 replication in the male genital tract, thereby increasing the number of HIV-1-infected cells and the local HIV-1 shedding in semen. The introduction of combination antiretroviral therapy has improved the life expectancy of HIV-1 infected individuals; however, there is evidence that systemic viral suppression does not always reflect full viral suppression in the seminal compartment. This review focus on the role semen leukocytes play in HIV-1 transmission and discusses implications of the increased resistance of cell-mediated transmission to immune-based prevention strategies.

SUBMITTER: Cavarelli M

PROVIDER: S-EPMC7553688 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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The importance of semen leukocytes in HIV-1 transmission and the development of prevention strategies.

Cavarelli Mariangela M Le Grand Roger R

Human vaccines & immunotherapeutics 20200702 9

HIV-1 sexual transmission occurs mostly through contaminated semen, which is a complex mixture of soluble factors with immunoregulatory functions and cells. It is well established that semen cells from HIV-1-infected men are able to produce the virus and that are harnessed to efficiently interact with mucosal barriers exposed during sexual intercourse. Several cofactors contribute to semen infectivity and may enhance the risk of HIV-1 transmission to a partner by increasing local HIV-1 replicati ...[more]

PMID: 32614649

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Project description:IntroductionAlthough strong scientific evidence of the efficacy and effectiveness of treatment-as-prevention (TasP) is available, full endorsement of the "Undetectable = Untransmittable" (U = U) and "zero-risk" messages could be improved. Increasing knowledge about HIV transmission, prevention and treatment is a critical component of care efforts. The study assessed knowledge of HIV transmission and prevention strategies, and the perceived accuracy of the slogan U = U among sexual and gender minorities (SGM) in Brazil.MethodsCross-sectional web-based survey targeting adult SGM living in Brazil (2021-2022) recruited on social media and dating apps. We used the 12-item HIV Knowledge Assessment (HIV-KA) questionnaire to assess HIV knowledge, three items of which address pre-exposure prophylaxis (PrEP), post-exposure prophylaxis and TasP. Perceived accuracy of the U = U slogan was assessed with the question: "With regards to HIV-positive individuals transmitting HIV through sexual contact, how accurate do you believe the slogan U = U is?". We a priori grouped the study population into three mutually exclusive groups: people living with HIV (PLHIV), HIV negative and HIV unknown. We used logistic regression models to assess factors associated with high HIV knowledge and perception of the U = U as completely accurate.ResultsOf 50,222 individuals accessing the questionnaire, 23,981 were included: 5071 (21.0%) PLHIV, 17,257 (71.5%) HIV negative and 1653 (6.9%) HIV unknown. The proportion of participants with high knowledge was significantly higher for PLHIV and HIV negative (48.1% and 45.5%, respectively) compared to 26.1% of HIV unknown. More PLHIV perceived U = U as completely accurate (80.4%), compared to 60.0% of HIV negative and 42.9% of HIV unknown. HIV knowledge correlates with perceived accuracy of the U = U slogan across all groups. Higher HIV knowledge was associated with higher income and education regardless of HIV status. Among HIV-negative participants, PrEP awareness and use were associated with higher knowledge and accurate perception of the U = U slogan.ConclusionsOur findings show that HIV knowledge and perceived accuracy of U = U are strongly correlated, that knowledge differs according to HIV status, and that poor socio-economic is linked to poor knowledge among SGM from Brazil. Educational strategies regarding TasP, U = U and zero risk targeting socio-economically vulnerable populations are urgent in Brazil.

Project description:BACKGROUND:Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART). OBJECTIVES:To determine if ART use in an HIV-infected member of an HIV-discordant couple is associated with lower risk of HIV transmission to the uninfected partner compared to untreated discordant couples. SEARCH METHODS:We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. SELECTION CRITERIA:Randomised controlled trials (RCT), cohort studies and case-control studies of HIV-discordant couples in which the HIV-infected member of the couple was being treated or not treated with ART DATA COLLECTION AND ANALYSIS: Abstracts of all trials identified by electronic or bibliographic scanning were examined independently by two authors. We initially identified 3,833 references and examined 87 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. MAIN RESULTS:One RCT and nine observational studies were included in the review. These ten studies identified 2,112 episodes of HIV transmission, 1,016 among treated couples and 1,096 among untreated couples. The rate ratio for the single randomised controlled trial was 0.04 [95% CI 0.00, 0.27]. All index partners in this study had CD4 cell counts at baseline of 350-550 cells/µL. Similarly, the summary rate ratio for the nine observational studies was 0.58 [95% CI 0.35, 0.96], with substantial heterogeneity (I(2)=64%). After excluding two studies with inadequate person-time data, we estimated a summary rate ratio of 0.36 [95% CI 0.17, 0.75] with substantial heterogeneity (I(2)=62%). We also performed subgroup analyses among the observational studies to see if the effect of ART on prevention of HIV differed by the index partner's CD4 cell count. Among couples in which the infected partner had ?350 CD4 cells/µL, we estimated a rate ratio of 0.12 [95% CI 0.01, 1.99]. In this subgroup, there were 247 transmissions in untreated couples and 30 in treated couples. AUTHORS' CONCLUSIONS:ART is a potent intervention for prevention of HIV in discordant couples in which the index partner has ?550 CD4 cells/µL. A recent multicentre RCT confirms the suspected benefit seen in earlier observational studies and reported in more recent ones. Questions remain about durability of protection, the balance of benefits and adverse events associated with earlier therapy, long-term adherence and transmission of ART-resistant strains to partners. Resource limitations and implementation challenges must also be addressed.Counselling, support, and follow up, as well as mutual disclosure, may have a role in supporting adherence, so programmes should be designed with these components. In addition to ART provision, the operational aspects of delivering such programmes must be considered.

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The importance of semen leukocytes in HIV-1 transmission and the development of prevention strategies.

Publications

The importance of semen leukocytes in HIV-1 transmission and the development of prevention strategies.

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