Hallett et al use a mathematical model to examine the long-term impact and cost-effectiveness of different pre-exposure prophylaxis (PrEP) strategies for HIV prevention in serodiscordant couples.
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.
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
Every year, about 2.5 million people become infected with HIV, the virus that causes AIDS. HIV is usually transmitted through unprotected sex with an HIV-infected partner. It destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. There is no cure for AIDS, although HIV can be held in check with antiretroviral therapy (ART), and there is no vaccine that protects against HIV infection. So, to halt the AIDS epidemic, other ways of preventing the spread of HIV are needed. Antiretroviral drugs could potentially be used in two ways to reduce HIV transmission. First, ART could be given to HIV-infected people before they need it for their own health to reduce their infectiousness; the World Health Organization currently recommends that HIV-positive people initiate ART when their CD4 count drops below 350 cells/µl blood but in many African countries ART is only initiated when CD4 counts fall below 200 cells/µl. Second, ART could be given to HIV-uninfected people to reduce acquisition of the virus. This approach—preexposure prophylaxis (PrEP)—has provided protection against HIV transmission in some but not all clinical trials.
Why Was This Study Done?
Couples in long-term relationships where one partner is HIV-positive and the other is HIV-negative (HIV serodiscordant couples) are a priority group for prevention interventions. In sub-Saharan Africa, where most new HIV infections occur, 10%–20% of stable partnerships are serodiscordant and condom use is often low, not least because such couples may want children. Earlier ART or PrEP might reduce HIV transmission in this group but the merits of different approaches have not been analyzed. In this study, the researchers use a mathematical model to examine the long-term impact and cost-effectiveness of different PrEP and ART strategies for HIV prevention in serodiscordant couples.
What Did the Researchers Do and Find?
The researchers constructed a model to simulate HIV infection and disease progression among hypothetical HIV serodiscordant stable heterosexual couples. The model incorporated data from South Africa on couple characteristics, disease progression, ART use, pregnancies, frequency of sex, and contact with other sexual partners, as well as estimates of the effectiveness of PrEP from clinical trials. The researchers used the model to compare the impact on HIV transmission, survival and quality of life, and the cost-effectiveness of no PrEP with four PrEP strategies—always use PrEP after diagnosis of HIV serodiscordancy, use PrEP up to and for a year after ART initiation by the HIV-infected partner (at a CD4 count of ≤200 cells/µl or ≤350 cells/µl), use PrEP only up to ART initiation by the infected partner, and use PrEP only while trying for a baby and during pregnancy. The model predicts, for example, that the cost per infection averted of PrEP used before ART initiation will be offset by future savings in lifelong treatment, particularly among couples with multiple partners, low condom use, and a high risk of transmission. To keep couples alive without the HIV-uninfected partner becoming infected, it could be more cost-effective to provide PrEP to the uninfected partner than to initiate ART earlier in the infected partner, provided the annual cost of PrEP is less than 40% of the annual cost of ART and PrEP is more than 70% effective. Finally, if PREP is 30%–60% effective, the most cost-effective strategy for couples could be to use PrEP in the uninfected partner prior to ART initiation in the infected partner at a CD4 count ≤350 cells/µl.
What Do These Findings Mean?
These findings suggest that the strategic use of PrEP and ART could cost-effectively reduce HIV transmission in HIV serodiscordant stable heterosexual couples in sub-Saharan Africa. The accuracy of these findings depends on the assumptions included in the mathematical model and on the data fed into it. In particular, the interpretation of these results is complicated by uncertainties in the likely cost of PrEP and the “real-world” effectiveness of PrEP. Nevertheless, these findings suggest that PrEP may become a valuable addition in some settings to existing approaches for HIV prevention such as condom promotion and male circumcision programs. Moreover, additional simulations with this mathematical model using more accurate information on the costs and effectiveness of PrEP could assist in future policy making decisions.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001123.
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and a section on PrEP
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on all aspects of HIV prevention, and on HIV/AIDS in Africa (in English and Spanish)
AVAC Global Advocacy for HIV Prevention provides up-to-date information on all aspects of HIV prevention, including PrEP
The US Centers for Disease Control and Prevention also has information on PrEP
WHO provides information about antiretroviral therapy
Patient stories about living with HIV/AIDS are available through Avert and through the charity website Healthtalkonline