Partners in Prevention HSV/HIV Transmission Study

Rationale

The majority of new HIV infections in Africa occur among HIV discordant couples (where one partner is HIV infected and one is uninfected). New ways to prevent HIV transmission in couples are desperately needed.

Among HIV infected adults worldwide, 80-90% have HSV-2 (genital herpes) infection. Genital ulcers, mainly due to HSV-2, have been shown to increase HIV transmission 5-fold. Although studies of HSV-2 suppression among HIV uninfected persons with HSV-2 infection (HPTN 039 and Mwanza) did not show a reduction in HIV acquisition, the door is still open for HSV-2 suppression in HIV infected persons to reduce HIV transmission. Partners in Prevention is evaluating whether the reduction in plasma and genital viral load with acyclovir will reduce HIV levels and transmission among HIV discordant couples. In the Partners study, acyclovir is given to the person already infected with HIV, whereas in HPTN 039 acyclovir was given to the HIV uninfected person at risk. Partners in Prevention will also provide important insights into whether HSV-2 suppression can delay HIV disease progression, including delaying time to initiation of antiretroviral therapy.

Study Description

The Partners in Prevention HSV/HIV Transmission Study is the largest trial of its kind with over 3,400 HIV discordant couples (where one partner is HIV infected, the other HIV uninfected) from 14 sites in 7 countries in Eastern and Southern Africa (Uganda, Kenya, Rwanda, Tanzania, Zambia, Botswana and South Africa).

The Partners in Prevention study is a randomized, double-blinded, placebo-controlled study to determine whether the use of acyclovir by people who are infected with both HSV-2 and HIV can reduce the likelihood that they will transmit HIV to their HIV uninfected sexual partners. During the study, the HSV/HIV infected partner takes 400 milligram (mg) twice daily for up to 24 months. Researchers randomly assigned half of the study volunteers to a group that received 400 mg acyclovir tablets; the other half received placebo tablets. None of the study volunteers, clinical staff or researchers knew which specific group the volunteers were assigned.

Sites are implementing couples counseling and HIV testing and educating communities about HIV discordance. Participants are provided with condoms, regular exams, and extensive counseling to reduce their risk for HIV infection throughout the study. Participants who become infected with HIV during the study are referred for appropriate medical care and treatment in their community.

For more information:

1. Backgrounder
2. External Q&A
3. Press Release (UW, May 2009)
4. Press Release (UW, January 2010)
5. ART Press Release (UW, May 2010)
6. ART Press Release (Lancet, May 2010)

Results

• Donnell D, Baeten JM, Kiarie J, Thomas KK, Stevens W, Cohen CR, McIntyre J, Lingappa JR, Celum C, for the Partners in Prevention HSV/HIV Transmission Study Team. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet 2010; 375(9731): 2092-2098.
• C. Celum, A. Wald, J.R. Lingappa, A.S. Magaret, R.S. Wang, N. Mugo, A. Mujugira, J.M. Baeten, J.I. Mullins, J.P. Hughes, E.A. Bukusi, C.R. Cohen, E. Katabira, A. Ronald, J. Kiarie, C. Farquhar, G.J. Stewart, J. Makhema, M. Essex, E. Were, K.H. Fife, G. de Bruyn, G.E. Gray, J.A. McIntyre, R. Manongi, S. Kapiga, D. Coetzee, S. Allen, M. Inambao, K. Kayitenkore, E. Karita, W. Kanweka, S. Delany, H. Rees, B. Vwalika, W. Stevens, M.S. Campbell, K.K. Thomas, R.W. Coombs, R. Morrow, W.L.H. Whittington, M.J. McElrath, L. Barnes, R. Ridzon, and L. Corey, for the Partners in Prevention HSV/HIV Transmission Study Team*. Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2. N Engl J Med. 2010; 362(5): 427-439.
• Lingappa J, Kahle E, Mugo N, Mujugira A, Magaret A, Baeten J, Bukusi EA, Cohen CR, Katabira E, Ronald A, Kiarie J, Farquhar C, John Stewart G, Makhema J, Essex M, Were E, Fife K, deBruyn G, Gray G, McIntyre J, Manongi R, Kapiga S, Coetzee D, Allen S, Inambao M, Kayitenkore K, Karita E, Kanweka W, Delany S, Rees H, Vwalika B, Coombs RW, Morrow R, Whittington W, Corey L, Wald A, Celum C for the Partners HSV-2/HIV-1 Transmission Study Team. Characteristics of HIV-1 Discordant Couples Enrolled in a Trial of HSV-2 Suppression to Reduce HIV-1 Transmission: The Partners Study. PLoS One. 2009; 4(4): e5272.
• Lingappa JR, Lambdin B, Bukusi EA, Ngure K, Kavuma L, Inambao M, Kanweka W, Allen S, Kiarie JN, Makhema J, Were E, Manongi R, Coetzee D, de Bruyn G, Delany-Moretlwe S, Magaret A, Mugo N, Mujugira A, Ndase P, Celum C; for the Partners in Prevention HSV-2/HIV Transmission Study Group. Regional Differences in Prevalence of HIV-1 Discordance in Africa and Enrollment of HIV-1 Discordant Couples into an HIV-1 Prevention Trial. PLoS ONE. 2008; 3 (1): e1411. PMCID: PMC2156103.