HIV-1 Treatment-as-Prevention: A Cohort Study Analysis of Serodiscordant Couples in Rural Southwest China.
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ABSTRACT:
SUBMITTER: Tang Z
PROVIDER: S-EPMC4616551 | biostudies-other | 2015 Jun
REPOSITORIES: biostudies-other
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Project description:The cost-effectiveness of early antiretroviral therapy (ART) in persons infected with human immunodeficiency virus (HIV) in serodiscordant couples is not known. Using a computer simulation of the progression of HIV infection and data from the HIV Prevention Trials Network 052 study, we projected the cost-effectiveness of early ART for such persons.For HIV-infected partners in serodiscordant couples in South Africa and India, we compared the early initiation of ART with delayed ART. Five-year and lifetime outcomes included cumulative HIV transmissions, life-years, costs, and cost-effectiveness. We classified early ART as very cost-effective if its incremental cost-effectiveness ratio was less than the annual per capita gross domestic product (GDP; $8,100 in South Africa and $1,500 in India), as cost-effective if the ratio was less than three times the GDP, and as cost-saving if it resulted in a decrease in total costs and an increase in life-years, as compared with delayed ART.In South Africa, early ART prevented opportunistic diseases and was cost-saving over a 5-year period; over a lifetime, it was very cost-effective ($590 per life-year saved). In India, early ART was cost-effective ($1,800 per life-year saved) over a 5-year period and very cost-effective ($530 per life-year saved) over a lifetime. In both countries, early ART prevented HIV transmission over short periods, but longer survival attenuated this effect; the main driver of life-years saved was a clinical benefit for treated patients. Early ART remained very cost-effective over a lifetime under most modeled assumptions in the two countries.In South Africa, early ART was cost-saving over a 5-year period. In both South Africa and India, early ART was projected to be very cost-effective over a lifetime. With individual, public health, and economic benefits, there is a compelling case for early ART for serodiscordant couples in resource-limited settings. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
| S-EPMC3913536 | biostudies-literature
Project description:Serodiscordant couples play an important role in maintaining the global HIV epidemic. This review summarizes biobehavioral and biomedical HIV prevention options for serodiscordant couples focusing on advances in 2013 and 2014, including World Health Organization guidelines and best evidence for couples counseling, couple-based interventions, and the use of antiviral agents for prevention. In the past few years, marked advances have been made in HIV prevention for serodiscordant couples and numerous ongoing studies are continuously expanding HIV prevention tools, especially in the area of pre-exposure prophylaxis. Uptake and adherence to antiviral therapy remains a key challenge. Additional research is needed to develop evidence-based interventions for couples, and especially for male-male couples. Randomized trials have demonstrated the prevention benefits of antiretroviral-based approaches among serodiscordant couples; however, residual transmission observed in recognized serodiscordant couples represents an important and resolvable challenge in HIV prevention.
| S-EPMC4267973 | biostudies-literature
Project description:IntroductionPre-exposure prophylaxis (PrEP) to prevent HIV infection is being rolled out in Africa. The uptake of PrEP to date has varied across populations and locations. We seek to understand the drivers of demand for PrEP through analysis of qualitative data collected in conjunction with a PrEP demonstration project involving East African HIV serodiscordant couples. Our goal was to inform demand creation by understanding what PrEP means - beyond HIV prevention - for the lives of users.MethodsThe Partners Demonstration Project evaluated an integrated strategy of PrEP and antiretroviral therapy (ART) delivery in which time-limited PrEP served as a "bridge" to long-term ART. Uninfected partners in HIV serodiscordant couples were offered PrEP at baseline and encouraged to discontinue once infected partners had taken ART for six months. We conducted 274 open-ended interviews with 93 couples at two Ugandan research sites. Interviews took place one month after enrolment and at later points in the follow-up period. Topics included are as follows: (1) discovery of serodiscordance; (2) decisions to accept/decline PrEP and/or ART; (3) PrEP and ART initiation; (4) experiences of using PrEP and ART; (5) PrEP discontinuation; (6) impact of PrEP and ART on the partnered relationship. Interviews were audio-recorded and transcribed. We used an inductive, content analytic approach to characterize meanings of PrEP stemming from its effectiveness for HIV prevention. Relevant content was represented as descriptive categories.ResultsDiscovery of HIV serodiscordance resulted in fear of HIV transmission for couples, which led to loss of sexual intimacy in committed relationships, and to abandonment of plans for children. As a result, partners became alienated from each other. PrEP countered the threat to the relationship by reducing fear and reinstating hopes of having children together. Condom use worked against the re-establishment of intimacy and closeness. By increasing couples' sense of protection against HIV infection and raising the prospect of a return to "live sex" (sex without condoms), PrEP was perceived by couples as solving the problem of serodiscordance and preserving committed relationships.ConclusionsThe most effective demand creation strategies for PrEP may be those that address the everyday life priorities of potential users in addition to HIV prevention.Clinical trial numberNCT02775929.
| S-EPMC6338102 | 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:We examined several measures of self-reported HIV risk behaviour in mutually disclosed sero-discordant couples over time to see if a couples counselling intervention was associated with changes in these behaviors.We analysed data from a prospective cohort study of HIV sero-discordant couples in Jinja, Uganda collected between June 2009 and December 2011. Participants received couples counselling, at 3-monthly intervals. We examined trends in reported condom-use, number of concurrent sexual partners, knowledge of HIV serostatus of concurrent partners and condom use of concurrent partners using Generalized Estimating Equation models, comparing responses at study enrollment with responses at six, 12 18 and 24 months of follow-up.A total of 586 couples were enrolled and the female member was HIV positive in 255 (44%) of them. The median age for female participants was 35 years and 42 years for men. Reported condom use at last sex with spouse increased over time (p<0.001) with the largest increases found among couples where the positive participant never received ART during the study(an increase from 68.8% at enrollment to 97.1% at 24 months). Male participants reported reductions in the number of concurrent sexual partners (p<0.001), increase in the knowledge of the HIV serostatus of these partners (p = 0.001) and a trend towards improved condom-use among non-primary partners (p = 0.070). Reported reduced risky behaviors did not wane over the study period.Couples counselling resulted in increased condom use among all participants and among men the intervention resulted in reductions in risk behaviour with concurrent sexual partners. Routine counselling for serodiscordant couples should be integrated in routine ART care programs.
| S-EPMC4575207 | biostudies-other
Project description:ObjectiveTo estimate the impact and cost-effectiveness of treatment as prevention (TasP), pre-exposure prophylaxis (PrEP) and condom promotion for serodiscordant couples in Nigeria.DesignMathematical and cost modelling.MethodsA deterministic model of HIV-1 transmission within a cohort of serodiscordant couples and to/from external partners was parameterized using data from Nigeria and other African settings. The impact and cost-effectiveness were estimated for condom promotion, PrEP and/or TasP, compared with a baseline where antiretroviral therapy (ART) was offered according to 2010 national guidelines (CD4 <350 cells/μl) to all HIV-positive partners. The impact was additionally compared with a baseline of current ART coverage (35% of those with CD4 <350 cells/μl). Full costs (in US $2012) of programme introduction and implementation were estimated from a provider perspective.ResultsSubstantial benefits came from scaling up ART to all HIV-positive partners according to 2010 national guidelines, with additional smaller benefits of providing TasP, PrEP or condom promotion. Compared with a baseline of offering ART to all HIV-positive partners at the 2010 national guidelines, condom promotion was the most cost-effective strategy [US $1206/disability-adjusted-life-year (DALY)], the next most cost-effective intervention was to additionally give TasP to HIV-positive partners (incremental cost-effectiveness ratio US $1607/DALY), followed by additionally giving PrEP to HIV-negative partners until their HIV-positive partners initiate ART (US $7870/DALY). When impact was measured in terms of infections averted, PrEP with condom promotion prevented double the number of infections as condom promotion alone.ConclusionsThe first priority intervention for serodiscordant couples in Nigeria should be scaled up ART access for HIV-positive partners. Subsequent incremental benefits are greatest with condom promotion and TasP, followed by PrEP.
| S-EPMC4568890 | biostudies-literature
Project description:There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV). Many social, clinical and genetic factors are known to contribute to the likelihood of HIV transmission, but there is little consensus on the relative importance and potential interaction of these factors. Additionally, recent studies of several variants in chemokine receptors have identified alleles that may be predictive of HIV transmission and disease progression; however the strengths and directions of the associations of these genetic markers with HIV transmission have markedly varied between studies. To better identify factors that predict HIV transmission in a Chinese population, 180 cohabiting serodiscordant couples were enrolled for study by the Henan Center for Disease Prevention and Control, and transmission and progression of HIV infection were regularly measured. We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study. We also assessed ten variants in three genes (CXCL12, CCR2, and CCR5) that have been shown to influence HIV transmission. We found two tightly linked variants in CCR2 and CCR5, rs1799864 and rs1800024, have a significant positive association with transmission as recessive models (OR>10, P value=0.011). Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use. These markers of transmission susceptibility may therefore serve to help stratify individuals by risk for HIV transmission.
| S-EPMC4465854 | biostudies-literature
Project description:Practice guidelines on pre-exposure prophylaxis (PrEP) for HIV serodiscordant couples recommend PrEP when the viral load of the partner living with HIV is either detectable or unknown. However, adherence to combination antiretroviral therapy is inconsistent, and research has found that individuals vulnerable to HIV place value on additional protective barriers. We conducted a prospective cohort study to assess the feasibility, perceptions, and adherence associated with periconceptional PrEP use among females without HIV and their male partners living with HIV across four academic medical centers in the United States. We performed descriptive statistics, McNemar's test of marginal homogeneity to assess discordance in female/male survey responses, and Spearman's correlation to determine associations between dried blood spot levels and female self-reported adherence to PrEP. We enrolled 25 women without HIV and 24 men living with HIV (one male partner did not consent to the study). Women took PrEP for a median of 10.9 months (interquartile range 3.8-12.0) and were generally adherent. In total, 87% of women (20/23) had a dried blood spot with >700 fmol/punch or ≥4 doses/week, 4% (1/23) at 350-699 fmol/punch or 2-3 doses/week, and 9% (2/23) at <350 fmol/punch or <2 doses/week (correlation between drug levels and adherence is based on prior data). Dried blood spot levels closely aligned with self-reported adherence (Spearman's rho = 0.64, p = 0.001). There were 10 pregnancies among 8 participants, 4 of which resulted in spontaneous abortions. There was one preterm delivery (36 5/7 weeks), no congenital abnormalities, and no HIV transmissions. Ten couples (40%) were either lost to follow-up or ended the study early. Overall, women attempting conception with male partners living with HIV in the United States are interested and able to adhere to PrEP as an additional tool for safer conception.
| S-EPMC7370981 | biostudies-literature
Project description:BackgroundAntiretroviral therapy (ART) was highly efficacious in preventing human immunodeficiency virus (HIV) transmission in stable serodiscordant couples in the HPTN-052 study, a resource-intensive randomized controlled trial with near-perfect ART adherence and mutual HIV status disclosure among all participating couples. However, minimal evidence exists of the effectiveness of ART in preventing HIV acquisition in stable serodiscordant couples in "real-life" population-based settings in hyperendemic communities of sub-Saharan Africa, where health systems are typically resource-poor and overburdened, adherence to ART is often low, and partners commonly do not disclose their HIV status to each other.MethodsData arose from a population-based open cohort in KwaZulu-Natal, South Africa. A total of 17 016 HIV-uninfected individuals present between January 2005 and December 2013 were included. Interval-censored time-updated proportional hazards regression was used to assess how the ART status affected HIV transmission risk in stable serodiscordant relationships.ResultsWe observed 1619 HIV seroconversions in 17 016 individuals, over 60 349 person-years follow-up time. During the follow-up period, 1846 individuals had an HIV-uninfected and 196 had an HIV-infected stable partner HIV incidence was 3.8/100 person-years (PY) among individuals with an HIV-infected partner (95% confidence interval [CI], 2.3-5.6), 1.4/100 PY (.4-3.5) among those with HIV-infected partners receiving ART, and 5.6/100 PY (3.5-8.4) among those with HIV-infected partners not receiving ART. Use of ART was associated with a 77% decrease in HIV acquisition risk among serodiscordant couples (adjusted hazard ratio, 0.23; 95% CI, .07-.80).ConclusionsART initiation was associated with a very large reduction in HIV acquisition in serodiscordant couples in rural KwaZulu-Natal. However, this "real-life" effect was substantially lower than the effect observed in the HPTN-052 trial. To eliminate HIV transmission in serodiscordant couples, additional prevention interventions are probably needed.
| S-EPMC4967606 | biostudies-literature
Project description:BackgroundAs sub-Saharan Africa transitions to a new era of universal antiretroviral therapy (ART), up-to-date assessments of population-level HIV RNA suppression are needed to inform interventions to optimise ART delivery. We sought to measure population viral load metrics to assess viral suppression and characterise demographic groups and geographical locations with high-level detectable viraemia in east Africa.MethodsThe Sustainable East Africa Research in Community Health (SEARCH) study is a cluster-randomised controlled trial of an HIV test-and-treat strategy in 32 rural communities in Uganda and Kenya, selected on the basis of rural setting, having an approximate population of 10 000 people, and being within the catchment area of a President's Emergency Plan for AIDS Relief-supported HIV clinic. During the baseline population assessment in the SEARCH study, we did baseline HIV testing and HIV RNA measurement. We analysed stable adult (aged ≥15 years) community residents. We defined viral suppression as a viral load of less than 500 copies per mL. To assess geographical sources of transmission risk, we established the proportion of all adults (both HIV positive and HIV negative) with a detectable viral load (local prevalence of viraemia). We defined transmission risk hotspots as geopolitical subunits within communities with an at least 5% local prevalence of viraemia. We also assessed serodiscordant couples, measuring the proportion of HIV-positive partners with detectable viraemia. The SEARCH study is registered with ClinicalTrials.gov, number NCT01864603.FindingsBetween April 2, 2013, and June 8, 2014, of 303 461 stable residents, we enumerated 274 040 (90·3%), of whom 132 030 (48·2%) were adults. Of these, 117 711 (89·2%) had their HIV status established, of whom 11 964 (10·2%) were HIV positive. Of these, we measured viral load in 8828 (73·8%) people. Viral suppression occurred in 3427 (81·6%) of 4202 HIV-positive adults on ART and 4490 (50·9%) of 8828 HIV-positive adults. Regional viral suppression among HIV-positive adults occurred in 881 (48·2%) of 1827 people in west Uganda, 516 (45·0%) of 1147 in east Uganda, and 3093 (52·8%) of 5854 in Kenya. Transmission risk hotspots occurred in three of 21 parishes in west Uganda and none in east Uganda and in 24 of 26 Kenya geopolitical subunits. In Uganda, 492 (2·9%) of 16 874 couples were serodiscordant: in 287 (58·3%) of these couples, the HIV-positive partner was viraemic (and in 69 [14·0%], viral load was >100 000 copies per mL). In Kenya, 859 (10·0%) of 8616 couples were serodiscordant: in 445 (53·0%) of these couples, the HIV-positive partner was viraemic (and in 129 [15%], viral load was >100 000 copies per mL).InterpretationBefore the start of the SEARCH trial, 51% of east African HIV-positive adults had viral suppression, reflecting ART scale-up efforts to date. Geographical hotspots of potential HIV transmission risk and detectable viraemia among serodiscordant couples warrant intensified interventions.FundingNational Institute of Allergy and Infectious Diseases (National Institutes of Health) and the President's Emergency Plan for AIDS Relief.
| S-EPMC5730457 | biostudies-literature