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Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study.

ABSTRACT:

Background

Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART) for HIV-1-infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP) for HIV-1-uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected) are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed.

Methods and findings

We constructed a mathematical model to examine the impact and cost-effectiveness of different strategies, including earlier initiation of ART and/or PrEP, for HIV-1 prevention for serodiscordant couples. Although the cost of PrEP is high, the cost per infection averted is significantly offset by future savings in lifelong treatment, especially among couples with multiple partners, low condom use, and a high risk of transmission. In some situations, highly effective PrEP could be cost-saving overall. To keep couples alive and without a new infection, providing PrEP to the uninfected partner could be at least as cost-effective as initiating ART earlier in the infected partner, if the annual cost of PrEP is <40% of the annual cost of ART and PrEP is >70% effective.

Conclusions

Strategic use of PrEP and ART could substantially and cost-effectively reduce HIV-1 transmission in HIV-1 serodiscordant couples. New and forthcoming data on the efficacy of PrEP, the cost of delivery of ART and PrEP, and couples behaviours and preferences will be critical for optimizing the use of antiretrovirals for HIV-1 prevention. Please see later in the article for the Editors' Summary.

SUBMITTER: Hallett TB

PROVIDER: S-EPMC3217021 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Publications

Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study.

Hallett Timothy B TB Baeten Jared M JM Heffron Renee R Barnabas Ruanne R de Bruyn Guy G Cremin Íde Í Delany Sinead S Garnett Geoffrey P GP Gray Glenda G Johnson Leigh L McIntyre James J Rees Helen H Celum Connie C

PLoS medicine 20111115 11

<h4>Background</h4>Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART) for HIV-1-infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP) for HIV-1-uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected) are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmis ...[more]

PMID: 22110407

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Project description:INTRODUCTION:High levels of HIV seroconcordance at the population level reduce the potential for effective HIV transmission. However, the level of HIV seroconcordance is largely unknown among heterosexual couples in sub-Saharan Africa. We aimed to quantify the population level HIV seroconcordance in stable heterosexual couples in rural South Africa. METHODS:We followed adults (≥15 years old) using a population-based, longitudinal and open surveillance system in KwaZulu-Natal, South Africa, from 2003 to 2016. Sexual partnerships and HIV status were confirmed via household surveys and annual HIV surveillance. We calculated the proportions of HIV seroconcordance and serodiscordance in stable sexual partnerships and compared them to the expected proportions under the assumption of random mixing using individual-based microsimulation models. Among unpartnered individuals, we estimated the incidence rates and hazard of sexual partnership formation with HIV-positive or HIV-negative partners by participants' own time-varying HIV status. Competing risks survival regressions were fitted adjusting for sociodemographic and clinical factors. We also calculated Newman's assortativity coefficients. RESULTS:A total of 18,341 HIV-negative and 11,361 HIV-positive individuals contributed 154,469 person-years (PY) of follow-up. Overall, 28% of the participants were in stable sexual partnerships. Of the 677 newly formed stable sexual partnerships, 7.7% (95% CI: 5.8 to 10.0) were HIV-positive seroconcordant (i.e. both individuals in the partnership were HIV-positive), which was three times higher than the expected proportion (2.3%) in microsimulation models based on random mixing. The incidence rates of sexual partnership formation were 0.54/1000PY with HIV-positive, 1.12/1000PY with HIV-negative and 2.65/1000PY with unknown serostatus partners. HIV-positive individuals had 2.39 (95% CI: 1.43 to 3.99) times higher hazard of forming a sexual partnership with an HIV-positive partner than did HIV-negative individuals after adjusting for age, opposite-sex HIV prevalence (by 5-years age groups), HIV prevalence in the surrounding community, ART coverage and other sociodemographic factors. Similarly, forming a sexual partnership with an HIV-negative partner was 1.47 (95% CI: 1.01 to 2.14) times higher in HIV-negative individuals in the adjusted model. Newman's coefficient also showed that assortativity by participant and partner HIV status was moderate (r = 0.35). CONCLUSIONS:A high degree of population level HIV seroconcordance (both positive and negative) was observed at the time of forming new sexual partnerships. Understanding factors driving these patterns may help the development of strategies to bring the HIV epidemic under control.

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.

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.).

Dataset Information

Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study.

Background

Methods and findings

Conclusions

Publications

Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study.

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