HIV sexual transmission is predominantly driven by single individuals rather than discordant couples: a model-based approach.
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ABSTRACT:
SUBMITTER: Champredon D
PROVIDER: S-EPMC3869741 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
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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.
| S-EPMC4026368 | biostudies-literature
Project description:A number of factors have been identified that are related to sexual and injecting HIV transmission. We developed a probabilistic mathematical model to put these factors together and interpret risks in the context of individual behavior among injecting drug-using (IDU) couples in St. Petersburg, Russia. Some HIV-discordant couples have unprotected sex and sometimes inject drugs together but stay discordant for a long time, while some individuals acquire HIV on the first encounter. We considered existing estimates of HIV transmission risks through injecting and sexual contacts to develop a predictive survival model for an individual who is exposed to HIV through intimate relationships. We computed simulated survival curves for a number of behavioral scenarios and discussed sources of simulated uncertainty. We then applied the model to a longitudinal study of HIV-discordant couples and validated the model's forecast. Although individual prediction of seroconversion time appeared impossible, the ability to rank behavioral patterns in terms of HIV risk and to estimate the probability of survival HIV-free will be important to educators and counselors.
| S-EPMC4026137 | biostudies-literature
Project description:OBJECTIVE:The study aims to understand the basis of continued HIV-1 transmission in Zambian and Rwandan HIV-1-discordant couples in the context of antiretroviral therapy (ART). DESIGN:We identified nine Zambian and seven Rwandan acutely infected, epidemiologically-linked couples from government couples' voluntary counseling and testing (CVCT) clinics where transmitting partners reported being on ART near the time of transmission. METHODS:We quantified viral load and plasma antiretroviral drug concentrations near the time of transmission and used these as surrogate measures for adherence. We also sequenced the polymerase gene from both donor and recipient partners to determine the presence of drug resistance mutations (DRMs). RESULTS:In Zambia, all transmitting partners had detectable viral loads, and 8/9 were not on therapeutic antiretroviral regimens. In the remaining couple, despite being on a therapeutic regimen, DRMs were present and transmitted. In Rwanda, although six of seven transmitting partners had detectable viral loads, therapeutic levels of antiretroviral drugs were detected in four of seven, but were accompanied by DRMs. In the remaining three couples, either no antiretrovirals or subtherapeutic regimens were detected. CONCLUSIONS:A reduction of ART effectiveness in nontrial settings was associated with lack of antiretrovirals in plasma and detectable viral load, and also drug resistance. In Zambia, where CVCT is not widely implemented, inconsistent adherence was high in couples unaware of their HIV discordance. In Rwanda, where CVCT is deployed country-wide, virologic failure was associated with drug resistance and subsequent transmission. Together, these findings suggest that increasing ART availability in resource-limited settings without risk reduction strategies that promote adherence may not be sufficient to control the HIV epidemic in the post-ART era.
| S-EPMC6211178 | biostudies-literature
Project description:INTRODUCTION:More new HIV-1 infections occur within stable HIV-1-discordant couples than in any other group in Africa, and sexually transmitted infections (STIs) may increase transmission risk among discordant couples, accounting for a large proportion of new HIV-1 infections. Understanding correlates of STIs among discordant couples will aid in optimizing interventions to prevent HIV-1 transmission in these couples. METHODS:HIV-1-discordant couples in which HIV-1-infected partners were HSV-2-seropositive were tested for syphilis, chlamydia, gonorrhea, and trichomoniasis, and HIV-1-uninfected partners were tested for HSV-2. We assessed sociodemographic, behavioral, and biological correlates of a current STI. RESULTS:Of 416 couples enrolled, 16% were affected by a treatable STI, and among these both partners were infected in 17% of couples. A treatable STI was found in 46 (11%) females and 30 (7%) males. The most prevalent infections were trichomoniasis (5.9%) and syphilis (2.6%). Participants were 5.9-fold more likely to have an STI if their partner had an STI (P<0.01), and STIs were more common among those reporting any unprotected sex (OR = 2.43; P<0.01) and those with low education (OR = 3.00; P<0.01). Among HIV-1-uninfected participants with an HSV-2-seropositive partner, females were significantly more likely to be HSV-2-seropositive than males (78% versus 50%, P<0.01). CONCLUSIONS:Treatable STIs were common among HIV-1-discordant couples and the majority of couples affected by an STI were discordant for the STI, with relatively high HSV-2 discordance. Awareness of STI correlates and treatment of both partners may reduce HIV-1 transmission. TRIAL REGISTRATION:ClinicalTrials.gov NCT00194519.
| S-EPMC2788224 | biostudies-literature
Project description:ObjectivesTo investigate sexual behaviours among HIV-discordant heterosexual couples and assess the correlates of condom use at the couple level.DesignCross-sectional study.SettingSeven prefectures along the Yangtze River in the Anhui Province, China.ParticipantsWe included 412 participants aged 18 years or older (206 married HIV-discordant couples).Primary and secondary outcome measuresIn this study, sexual behaviours included marital or extramarital sex in the past 6 months, as well as the frequency of marital sex and condom use (always, sometimes or never) if having marital sex in the past 6 months. We used stepwise ordinal logistic regression modelling to determine the correlates of condom use.ResultsIn total, 63.1% (130 of 206) of couples had marital sex in the past 6 months, of which 89.2% (116 of 130) used condoms consistently. Couples with more marital duration (OR=1.15; 95% CI: 1.03, 1.28) were more inclined to adhere to condom use, whereas those lacking support and care (OR=0.25; 95% CI: 0.07, 0.94) and being remarried (OR=0.08; 95% CI: 0.02, 0.43) were associated with less condom use. In addition, HIV-positive respondents were more likely to have extramarital sex than HIV-negative respondents (p=0.015).ConclusionsThe extramarital sex of HIV-positive spouses should be considered. Implementation of interventions, such as increasing support and care between spouses to promote marital intimacy and stability, could reduce unprotected sexual behaviour.
| S-EPMC10277063 | biostudies-literature
Project description:Differences in immune control of HIV-1 infection are often attributable to the highly variable HLA class I molecules that present viral epitopes to CTL. In our immunogenetic analyses of 429 HIV-1 discordant Zambian couples (infected index partners paired with cohabiting seronegative partners), several HLA class I variants in index partners were associated with contrasting rates and incidence of HIV-1 transmission within a 12-year study period. In particular, A*3601 on the A*36-Cw*04-B*53 haplotype was the most unfavorable marker of HIV-1 transmission by index partners, while Cw*1801 (primarily on the A*30-Cw*18-B*57 haplotype) was the most favorable, irrespective of the direction of transmission (male to female or female to male) and other commonly recognized cofactors of infection, including age and GUI. The same HLA markers were further associated with contrasting viral load levels in index partners, but they had no clear impact on HIV-1 acquisition by the seronegative partners. Thus, HLA class I gene products not only mediate HIV-1 pathogenesis and evolution but also influence heterosexual HIV-1 transmission.
| S-EPMC2570252 | biostudies-literature
Project description:BACKGROUND:In Kenya and much of sub-Saharan Africa, nearly half of all couples affected by HIV are discordant. Antiretroviral therapy (ART) slows disease progression in HIV-1-infected individuals and reduces transmission to uninfected partners. We examined time to ART initiation and factors associated with delayed initiation in HIV-1-discordant couples in Nairobi. METHODS:HIV-1-discordant couples were enrolled and followed quarterly for up to 2 years. Clinical staff administered questionnaires and conducted viral loads and CD4 counts. Participants with a CD4 count meeting ART criteria were referred to a nearby US President's Emergency Plan for AIDS Relief-funded treatment center. Barriers to ART initiation among participants with a CD4 count eligible for ART were assessed by Cox regression. RESULTS:Of 439 HIV-1-infected participants (63.6% females and 36.4% males), 146 met CD4 count criteria for ART during follow-up. Median time from meeting CD4 criteria until ART initiation was 8.9 months, with 42.0% of eligible participants on ART by 6 months and 63.4% on ART by 1 year. The CD4 count at the time of eligibility was inversely associated with time to ART initiation (hazard ratio = 0.49, P < 0.001). Compared with homeowners, those paying higher rents started ART 48% more slowly (P = 0.062) and those paying lower rents started 71% more slowly (P = 0.002). CONCLUSIONS:Despite access to regular health care, referrals to treatment centers, and free access to ART, over one-third of participants with an eligible CD4 count had not started ART within 1 year. Factors of lower socioeconomic status may slow ART initiation, and targeted approaches are needed to avoid delays in treatment initiation.
| S-EPMC3202340 | biostudies-literature
Project description:BackgroundThe number of strategies to prevent HIV transmission has increased following trials evaluating antiretroviral therapy (ART), preexposure prophylaxis (PrEP) and male circumcision. Serodiscordant couples need guidance on the effects of these strategies alone, and in combination with each other, on HIV transmission.MethodsWe estimated the sexual risk of HIV transmission over 1-year and 10-year periods among male-male and male-female serodiscordant couples. We assumed the following reductions in transmission: 80% from consistent condom use; 54% from circumcision in the negative male partner of a heterosexual couple; 73% from circumcision in the negative partner of a male-male couple; 71% from PrEP in heterosexual couples; 44% from PrEP in male-male couples; and 96% from ART use by the HIV-infected partner.FindingsFor couples using any single prevention strategy, a substantial cumulative risk of HIV transmission remained. For a male-female couple using only condoms, estimated risk over 10 years was 11%; for a male-male couple using only condoms, estimated risk was 76%. ART use by the HIV-infected partner was the most effective single strategy in reducing risk; among male-male couples, adding consistent condom use was necessary to keep the 10-year risk below 10%.ConclusionFocusing on 1-year and longer term transmission probabilities gives couples a better understanding of risk than those illustrated by data for a single sexual act. Long-term transmission probabilities to the negative partner in serodiscordant couples can be high, though these can be substantially reduced with the strategic use of preventive methods, especially those that include ART.
| S-EPMC7797164 | biostudies-literature
Project description:BackgroundIn HIV discordant couples (one parther is HIV-infected, another is HIV-uninfected) HIV-negative partners often remain uninfected for a long time despite long, stable, often unprotected sexual contacts with HIV-infected partner. The increase of time of living together accompanying the decrease of the incidence of HIV infection in HIV-negative partner. The features of HIV-specific immune response in HIV discorgant couples was investigated.MethodsThirty-three HIV discordant couples from Moscow region living together <1 year (2 couples), 1 to 3 years (18 couples), 4 to 5 years (9 couples), 6 to 10 years (4 couples) were included in the investigation. Sera of 33 HIV-uninfected partners from HIV discordant couples (17 men and 16 women) were tested for HIV-specific antibodies by enzyme immunoassay and immunoblot. Viral load was estimated by polymerase chain reaction (PCR).ResultsAntibodies against HIV gp160 were detected in 3 persons (9,1%), against p68/66—in 3 persons (9,1%), against p52/51—in 3 persons (9,1%), against g34/31—in 3 persons (9,1%); total—in 6 persons (18,2%). All of them were defined as HIV-uninfected by PCR. In 4 of 6 persons HIV-specific antibodies were not detected after finishing of risk behavior.ConclusionsIt is possible to suggest that detected antibodies against HIV gp160, p68/66, p52/51, p34/31 in HIV-uninfected people are caused by contact with HIV (according to literature data, non-specific stimulation may cause the appearance of antibodies binding the other HIV antigens: p55, p24/25 and g18) and may contribute to maintainance of HIV-negative status of uninfected partners in HIV-discordant couples. The cohort of high exposed but HIV-uninfected people was formed during immunological monitoring of HIV discordant couples in Moscow region. This cohort is available for systematic observation and is perspective for further investigation of mechanisms of resistance to HIV infection and correlates of immune protection. Now the cohort is expanded.
| S-EPMC3512641 | biostudies-other
Project description:The Partners HSV-2/HIV-1 Transmission Study (Partners Study) is a phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2) suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to their HIV-1 susceptible partners, which requires recruitment of HIV-1 serodiscordant heterosexual couples. We describe the baseline characteristics of this cohort.HIV-1 serodiscordant heterosexual couples, in which the HIV-1 infected partner was HSV-2 seropositive, had a CD4 count >or=250 cells/mcL and was not on antiretroviral therapy, were enrolled at 14 sites in East and Southern Africa. Demographic, behavioral, clinical and laboratory characteristics were assessed.Of the 3408 HIV-1 serodiscordant couples enrolled, 67% of the HIV-1 infected partners were women. Couples had cohabitated for a median of 5 years (range 2-9) with 28% reporting unprotected sex in the month prior to enrollment. Among HIV-1 susceptible participants, 86% of women and 59% of men were HSV-2 seropositive. Other laboratory-diagnosed sexually transmitted infections were uncommon (<5%), except for Trichomonas vaginalis in 14% of HIV-1 infected women. Median baseline CD4 count for HIV-1 infected participants was 462cells/mcL and median HIV-1 plasma RNA was 4.2 log(10) copies/mL. After adjusting for age and African region, correlates of HIV-1 RNA level included male gender (+0.24 log(10) copies/mL; p<0.001) and CD4 count (-0.25 and -0.55 log(10) copies/mL for CD4 350-499 and >500 relative to <350, respectively, p<0.001).The Partners Study successfully enrolled a cohort of 3408 heterosexual HIV-1 serodiscordant couples in Africa at high risk for HIV-1 transmission. Follow-up of this cohort will evaluate the efficacy of acyclovir for HSV-2 suppression in preventing HIV-1 transmission and provide insights into biological and behavioral factors determining heterosexual HIV-1 transmission.ClinicalTrials.gov NCT00194519.
| S-EPMC2671170 | biostudies-literature