Dataset Information

Partner characteristics predicting HIV-1 set point in sexually acquired HIV-1 among African seroconverters.

ABSTRACT: Plasma HIV-1 RNA set point is an important predictor of HIV-1 disease progression. We hypothesized that inoculum size and HIV-1 exposure prior to HIV-1 transmission may modulate set point. We evaluated predictors of set point among 141 African HIV-1 seroconverters and their HIV-1-infected study partners. We compared characteristics of seroconverters and their HIV-1-infected partners and HIV-1 set point. Data were from a clinical trial of genital HSV-2 suppression with acyclovir to reduce HIV-1 transmission in HIV-1 serodiscordant couples with HIV-1 transmission linkage assigned through virus sequencing. Our analysis includes data from all transmissions including those with transmission linkage to the HIV-1-infected "source partner" and those that were not linked to their HIV-1-infected study partner. In multivariable analysis, higher plasma HIV-1 in source partners was associated with higher seroconverter set point ( + 0.44 log10 copies/ml per log(10) source partner plasma HIV-1, p < 0.001). In addition, bacterial vaginosis (BV) among female source partners near the time of infection was associated with higher set point in their male seroconverters ( + 0.49 log(10), p = 0.04). Source partner characteristics associated with lower set point included male circumcision ( - 0.63 log(10), p = 0.03) and assignment to acyclovir ( - 0.44 log10, p = 0.02). The proportion of variation in set point explained by plasma HIV-1 RNA of the source partner, after controlling for other factors, was 0.06. Source partner plasma HIV-1 level is the most significant predictor of seroconverter set point, possibly reflecting characteristics of the transmitted virus. Acyclovir use, BV among women source partners, and circumcision among male source partners may alter the set point by affecting transmitted virus inoculum in the source partners' genital compartment.

SUBMITTER: Lingappa JR

PROVIDER: S-EPMC3537302 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Partner characteristics predicting HIV-1 set point in sexually acquired HIV-1 among African seroconverters.

Lingappa Jairam R JR Thomas Katherine K KK Hughes James P JP Baeten Jared M JM Wald Anna A Farquhar Carey C de Bruyn Guy G Fife Kenneth H KH Campbell Mary S MS Kapiga Saidi S Mullins James I JI Celum Connie C

AIDS research and human retroviruses 20130101 1

Plasma HIV-1 RNA set point is an important predictor of HIV-1 disease progression. We hypothesized that inoculum size and HIV-1 exposure prior to HIV-1 transmission may modulate set point. We evaluated predictors of set point among 141 African HIV-1 seroconverters and their HIV-1-infected study partners. We compared characteristics of seroconverters and their HIV-1-infected partners and HIV-1 set point. Data were from a clinical trial of genital HSV-2 suppression with acyclovir to reduce HIV-1 t ...[more]

PMID: 23061422

Similar Datasets

Project description:UnlabelledWe quantified the collective impact of source partner HIV-1 RNA levels, human leukocyte antigen (HLA) alleles, and innate responses through Toll-like receptor (TLR) alleles on the HIV-1 set point. Data came from HIV-1 seroconverters in African HIV-1 serodiscordant couple cohorts. Linear regression was used to determine associations with set point and R(2) to estimate variation explained by covariates. The strongest predictors of set point were HLA alleles (B*53:01, B*14:01, and B*27:03) and plasma HIV-1 levels of the transmitting partner, which explained 13% and 10% of variation in set point, respectively. HLA-A concordance between partners and TLR polymorphisms (TLR2 rs3804100 and TLR7 rs179012) also were associated with set point, explaining 6% and 5% of the variation, respectively. Overall, these factors and genital factors of the transmitter (i.e., male circumcision, bacterial vaginosis, and use of acyclovir) explained 46% of variation in set point. We found that both innate and adaptive immune responses, together with plasma HIV-1 levels of the transmitting partner, explain almost half of the variation in viral load set point.ImportanceAfter HIV-1 infection, uncontrolled virus replication leads to a rapid increase in HIV-1 concentrations. Once host immune responses develop, however, HIV-1 levels reach a peak and subsequently decline until they reach a stable level that may persist for years. This stable HIV-1 set point represents an equilibrium between the virus and host responses and is predictive of later disease progression and transmission potential. Understanding how host and virus factors interact to determine HIV-1 set point may elucidate novel mechanisms or biological pathways for treating HIV-1 infection. We identified host and virus factors that predict HIV-1 set point in people who recently acquired HIV-1, finding that both innate and adaptive immune responses, along with factors that likely influence HIV-1 virulence and inoculum, explain ∼46% of the variation in HIV-1 set point.

Project description:BACKGROUND:Partner notification is an essential component of sexually transmitted infection (STI) management. The process involves identifying exposed sex partner(s), notifying these partner(s) about their exposure to a curable STI, and offering counselling and treatment for the STI as a part of syndromic management or after results from an STI test. When implemented effectively, partner notification services can prevent the index patient from being reinfected with a curable STI from an untreated partner, reduce the community burden of curable STIs, and prevent adverse health outcomes in both the index patient and his or her sex partner(s). However, partner notification and treatment rates are often low. This study seeks to explore experiences and preferences related to partner notification and treatment for curable STIs among pregnant women receiving care in an antenatal clinic with integrated HIV and curable STI testing. Results are intended to inform efforts to improve partner notification and treatment rates in Southern Africa. METHODS:We conducted qualitative interviews among women diagnosed with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and/or Trichomonas vaginalis (TV) infection while seeking antenatal care in Gaborone, Botswana. Semi-structured interviews were used to obtain women's knowledge about STIs and their experiences and preferences regarding partner notification. RESULTS:Fifteen women agreed to participate in the study. The majority of women had never heard of CT, NG, or TV infections prior to testing. Thirteen out of 15 participants had notified partners about the STI diagnosis. The majority of notified partners received some treatment; however, partner treatment was often delayed. Most women expressed a preference for accompanying partners to the clinic for treatment. Experiences and preferences did not differ by HIV infection status. CONCLUSIONS:The integration of STI, HIV, and antenatal care services may have contributed to most women's willingness to notify partners. However, logistical barriers to partner treatment remained. More research is needed to identify effective and appropriate strategies for scaling-up partner notification services in order to improve rates of partners successfully contacted and treated, reduce rates of STI reinfection during pregnancy, and ultimately reduce adverse maternal and infant outcomes attributable to antenatal STIs.

Dataset Information

Partner characteristics predicting HIV-1 set point in sexually acquired HIV-1 among African seroconverters.

Publications

Partner characteristics predicting HIV-1 set point in sexually acquired HIV-1 among African seroconverters.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets