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HIV-1 transmission among HIV-1 discordant couples before and after the introduction of antiretroviral therapy in Rakai, Uganda. AIDS.
Global Health Sciences Literature Digest
Published March 28, 2011
Journal Article

Reynolds SJ, Makumbi F, Nakigozi G, Kagaayi J, Gray RH, Wawer M, Quinn TC, Serwadda D. HIV-1 transmission among HIV-1 discordant couples before and after the introduction of antiretroviral therapy in Rakai, Uganda. AIDS. 2011 Feb 20;25(4):473-7.


To evaluate the effect of antiretroviral therapy (ART) on HIV transmission rates between HIV-discordant couples.


Rural Rakai District, Uganda.

Study Design

Observational cohort; retrospective analysis.


Married HIV sero-discordant couples (including polygamous unions), aged 15-49.

Main Outcomes:

HIV incidence and risk behavior in the HIV uninfected partner; values were compared in the period prior to initiation of ART by the HIV positive partner compared to the period following ART initiation.


HIV discordant couples were identified through the Rakai Community Cohort Study (RCCS) that began delivering free ART in the district in 2004. The RCCS administered health, behavioral, and HIV screening annually to 15,000 persons aged 15-49 years in 50 villages through 17 mobile clinics, and counseled participants on HIV risk reduction strategies. ART was provided for those found to be HIV positive whose CD4 cell count was ≤250 cells/µl, or who had WHO Stage IV disease (total of more than 2,100 persons on ART to-date). Viral load testing was performed every six months among those on ART.

In this analysis, data from four survey rounds from 2004-9 were analyzed, and discordant couples were retrospectively identified. The first visit in which discordance was identified was considered baseline. The HIV uninfected partner was followed until seroconversion or censoring at death, separation, outmigration, or last survey visit.


From 2004 to 2009, 250 HIV discordant couples were identified, among whom 32 HIV positive index partners started ART. At baseline, 58% of couples had a male HIV positive partner; only 4% practiced consistent condom use; 40% of HIV-negative partners drank alcohol before sex; 20% of men were circumcised; 20% of men were polygamous. The median follow-up time before ART initiation was 1.57 years, and median follow-up after ART was 1.54 years. Prior to ART initiation, the incidence of seroconversion among negative partners was 9.2 per 100 person-years (py) with 42 seroconversions/493 py. In the period following ART initiation, there were zero seroconversions/54 py (p<0.01). There were no significant differences in gender, age, male circumcision status, number of sexual partners in the last 12 months, or self-reported genital ulcer disease between the period before compared to after ART initiation. However, following ART initiation, risk behaviors were significantly reduced: 54% of couples always used a condom vs. 12.5% prior to ART (p<0.001). Sexual frequency (>4 episodes in the last month) decreased, (40% vs. 20%, p=0.08); alcohol use before sex with any partner declined (40% vs. 24%, p=0.06). At six months, 20 of 28 (71%) partners tested and on treatment had viral loads <400 copies/ml; the other 8 had <2000 copies/ml. All 28 clients with viral load testing at 24 months had <400 viral copies/ml.


The use of ART by the HIV positive partner in sero-discordant couples is likely to have reduced HIV transmission in sero-discordant couples in this rurally-based study. However, the authors state it was not possible to distinguish between the effect of reduced viral load and improved risk reduction, but conclude that it is likely to be due to the use of ART.

Quality Rating

As this observational study only enrolled a modest number of sero-discordant couples (n=250) and only few persons on ART (n=42) with limited total follow-up on treatment (54 py), generalizability of the findings is limited. Details of findings (such as results of multivariable regression models) were not provided, but this may have been due to the fact that the article was a ‘concise communication.’

In Context

Studies have shown that viral load is the most important determinant of HIV transmission risk in discordant couples, and other observational studies have reported a reduction in transmission among discordant couples in which one partner is on ART. (1,2,3,4,5) The ongoing HIV Prevention Trials Network 052 study will be better able to determine whether and to what degree ART can prevent HIV transmission between couples.(6)

Programmatic Implications

This study adds support for the hypothesis that use of ART with subsequent reduction of viral load can reduce transmission of HIV. Evidence has accumulated that this occurs in discordant couples, but the extent to which large scale use of ART can reduce incidence at the population level is not yet clear.


  1. Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, Wabwire-Mangen F, Meehan MO, Lutalo T, Gray RH. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. 2000 Mar 30;342(13):921-9.
  2. Ronald H Gray, Maria J Wawer, Ron Brookmeyer, Nelson K Sewankambo, David Serwadda, Fred Wabwire-Mangen, Tom Lutalo,Xianbin Li, Thomas vanCott, Thomas C Quinn, and the Rakai Project Team. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet. 2001; 357: 1149–53
  3. Castilla J, Del Romero J, Hernando V, Marincovich B, García S, Rodríguez C. Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV. J Acquir Immune Defic Syndr. 2005 Sep 1;40(1):96-101
  4. Sullivan, P., Kayitenkore, K., Chomba, E. Reduction of HIV transmission risk and high risk sex while prescribed ART: results from discordant couples in Rwanda and Zambia. 2009 Oral abstract session: 15th Conference on Retrovirus and Opportunistic Infections
  5. Porco TC, Martin JN, Page-Shafer KA, Cheng A, Charlebois E, Grant RM, Osmond DH. Decline in HIV infectivity following the introduction of highly active antiretroviral therapy. AIDS. 2004 Jan 2;18(1):81-8.
  6. Kumarasamy et al. Antiretroviral therapy to prevent the sexual transmission of HIV-1 and reduce HIV-1 associated morbidity and mortality: baseline data from HPTN 052.Abstract no. MOPE0398. XVIII International AIDS Conference (2010).