Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.


BACKGROUND
Bill & Melinda Gates Foundation; US National Institutes of Health.
Donnell
Deborah
D
Statistical Center for HIV/AIDS Research and Prevention and the Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. deborah@fhcrc.org
Baeten
Jared M
JM
Kiarie
James
J
Thomas
Katherine K
KK
Stevens
Wendy
W
Cohen
Craig R
CR
McIntyre
James
J
Lingappa
Jairam R
JR
Celum
Connie
C
D015492:AIDS Serodiagnosis; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D018258:Herpesvirus 2, Human / Q000302:isolation & purification; D020010:Heterosexuality; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D012747:Sexual Partners; D014146:Training Support
D044966:Anti-Retroviral Agents; D012367:RNA, Viral