Donnell D, Baeten JM, Kiarie J, et al.. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort study

Statistical Center for HIV/AIDS Research and Prevention and the Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
The Lancet (Impact Factor: 45.22). 06/2010; 375(9731):2092-8. DOI: 10.1016/S0140-6736(10)60705-2
Source: PubMed


High plasma HIV-1 RNA concentrations are associated with increased risk of HIV-1 transmission. Initiation of antiretroviral therapy (ART) reduces plasma HIV-1 concentrations. We aimed to assess the effect of ART use by patients infected with HIV-1 on risk of transmission to their uninfected partners.
Participants in our prospective cohort analysis were from a randomised placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus type 2, and their HIV-1 seronegative partners. At enrolment, HIV-1 infected participants had CD4 counts of 250 cells per microL or greater and did not meet national guidelines for ART initiation; during 24 months of follow-up, CD4 counts were measured every 6 months and ART was initiated in accordance with national guidelines. Uninfected partners were tested for HIV-1 every 3 months. The primary outcome was genetically-linked HIV-1 transmission within the study partnership. We assessed rates of HIV-1 transmission by ART status of infected participants.
3381 couples were eligible for analysis. 349 (10%) participants with HIV-1 initiated ART during the study, at a median CD4 cell count of 198 (IQR 161-265) cells per microL. Only one of 103 genetically-linked HIV-1 transmissions was from an infected participant who had started ART, corresponding to transmission rates of 0.37 (95% CI 0.09-2.04) per 100 person-years in those who had initiated treatment and 2.24 (1.84-2.72) per 100 person-years in those who had not-a 92% reduction (adjusted incidence rate ratio 0.08, 95% CI 0.00-0.57, p=0.004). In participants not on ART, the highest HIV-1 transmission rate (8.79 per 100 person-years) was from those with CD4 cell counts lower than 200 cells per microL. In couples in whom the untreated HIV-1 infected partner had a CD4 cell count greater than 200 cells per microL, 66 (70%) of 94 transmissions occurred when plasma HIV-1 concentrations exceeded 50 000 copies per mL.
Low CD4 cell counts and high plasma HIV-1 concentrations might guide use of ART to achieve an HIV-1 prevention benefit. Provision of ART to HIV-1 infected patients could be an effective strategy to achieve population-level reductions in HIV-1 transmission.
Bill & Melinda Gates Foundation; US National Institutes of Health.

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    • "However, on the other hand, timely HIV testing provides the benefits of reduction of the spread of the virus and continued health of infected individuals through access to HIV health care services. Several studies have shown that patients who initiate early ART are less likely to spread the virus [6] [7] [8] . "
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    • "Data used for each setting came from various sources: Tallinn (Dehne, 1999; Uuskula et al., 2008, 2011; Uuskula, Des Jarlais, Raag, Pinkerton, & Feelemyer, 2014; Wilson et al., 2007); St. Petersburg (Abdala et al., 2003a, 2003b, 2008; Gyarmathy et al., 2009; Karapetyan et al., 2002; Kozlov et al., 2006; Niccolai et al., 2009, 2010, 2011; Rhodes, Sarang, Bobrik, Bobkov, & Platt, 2004; Smol'skaia et al., 2000); and Dushanbe (Abdulloev, Dekhkanova, & Ayombekov, 2008; Abdulloev, Rajabov, & Shabonov, 2009; Beyrer et al., 2009; Dekhkanova, 2006; Latypov et al., 2014; Nurliaminova, 2007; Tumanov, Asadulloev, & Chariev, 2010). on results of recent trials and prospective studies among serodiscordant heterosexual couples that have shown a 90% or greater reduction in HIV infectivity when one sexual partner is on ART (Cohen et al., 2011; Donnell et al., 2010), but adjusted downwards for the lower adherence levels frequently achieved among PWID (Malta, Magnanini, Strathdee, & Bastos, 2010; Nolan et al., 2011; Wood et al., 2003) which are likely to increase viral load (Bangsberg et al., 2000; Braithwaite et al., 2007; Gross, Bilker, Friedman, & Strom, 2001; Petersen et al., 2007). For simplicity, it is assumed that all HIV positive PWID (except those in the initial acute phase) can be recruited on to ART at a fixed rate. "
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