Combined antiretroviral treatment and heterosexual transmission of HIV-1: cross sectional and prospective cohort study. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. HIV transmission risk among serodiscordant couples: a retrospective study of former plasma donors in Henan, China. Sexual transmission of HIV-1 among serodiscordant couples in Porto Alegre, southern Brazil. HIV-1 transmission among HIV-1 discordant couples before and after the introduction of antiretroviral therapy. Antiretroviral treatment of men infected with human immunodeficiency virus type 1 reduces the incidence of heterosexual transmission. Italian Study Group on HIV Heterosexual Transmission.
To estimate the risk and probability of heterosexual transmission of HIV-1 from infected people taking combined antiretroviral treatment.
                Cross sectional and prospective cohort studies.
                HIV clinic in Madrid, Spain.
                Stable heterosexual couples with one partner with HIV-1 infection (index partner) and the other reporting this sexual relationship as the only risk exposure.
                HIV seroprevalence in non-index partners at enrolment and seroconversions in follow-up according to antiretroviral treatment taken by the index partner.
                In 476 couples in which the index partner was not taking antiretroviral treatment, HIV seroprevalence at enrolment in non-index partners was 9.2% (n=44), whereas in 149 couples in which the index partner was taking combined antiretroviral therapy no partner was infected (P<0.001). During follow-up, the 341 serodiscordant couples in which the index partner was not taking antiretroviral treatment had about 11 000 acts of intercourse without condoms, 50 natural pregnancies, and five HIV seroconversions (0.0004 per unprotected intercourse; 95% confidence interval 0.0001 to 0.0010); 294 of these couples always used condoms, accounting for about 42 000 acts of intercourse, 136 risk exposures from condom failure, and one HIV seroconversion. The relative risk associated with condom use was 0.07 (0.01 to 0.58). In 144 couples the index partner was taking combined antiretroviral treatment; they accounted for over 7000 unprotected acts of intercourse and 47 natural pregnancies but no HIV seroconversion (0 to 0.0005 per unprotected intercourse).
                The heterosexual infectivity of HIV-1 in individuals taking effective antiretroviral treatment is low. Avoidance of unprotected intercourse and receipt of antiretroviral treatment by the infected partner in accordance with protocols are complementary measures to prevent HIV transmission. 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.
                Copyright 2010 Elsevier Ltd. All rights reserved. OBJECTIVES: To estimate the HIV incidence and assess the behavioral, clinical, and quality-of-life risk factors for HIV transmission among serodiscordant couples from Henan Province, China. METHODS: Between January 2006 and December 2008, initially seronegative spouses were tested for HIV at six month intervals. Retrospectively identified subjects were interviewed through face-to-face questionnaire. Cox proportional-hazards model was used to assess the relationship between risk factors and HIV seroconversion. RESULTS: Out of 1927 couples, 84 (4.3%) seroconversions occurred, representing a seroconversion rate of 1.71 per 100 person-years. Seroconversion rates increased over time. Not always using condoms (RR=8.42; 95% CI, 4.83-14.67), sexual activity ≥ 4 times per month (RR=5.24; 95% CI, 2.55-10.77), not switching anti-retroviral treatment regimen (RR=1.99; 95% CI, 0.85-4.65), and a quality of life score <12 on the psychological domain (RR=2.33; 95% CI, 1.21-4.48) were associated with increased risk of seroconversion. Seventy one percent of index spouses were on ART. There was no association between rate of HIV seroconversion and last recorded CD4 cell count level of the index spouse. CONCLUSIONS: Effective HIV prevention interventions targeting discordant couples should focus on sustaining health education, increasing psychosocial support services, and increasing medication adherence monitoring. A cohort of 93 heterosexual HIV serodiscordant couples with no prior antiretroviral use were identified in a large referral center from February 2000 to January 2006 in southern Brazil.
                Review of clinic records retrospectively identified 56 cases of untreated index cases whereas 37 couples were identified prospectively. Demographics, medical, and laboratory data were obtained. During follow-up, 41/93 index cases (44%) initiated antiretrovirals (ARVs) and from 52 without ARV use, 4 were lost to follow-up. Median viral loads were used to compare transmitters versus nontransmitters (Mann-Whitney test).
                Sixty-seven (72%) index cases were female (49% identified during ante-natal care). Unprotected sexual intercourse as a risk factor for HIV-1 infection was significantly higher as compared to intravenous drug use (P < 0.0001) in female index partners but not in male index cases. Sexually transmitted diseases were identified in 22 cases (24%). Six HIV-1 seroconversions occurred (6.5%). In all cases index partners were not using ARVs at the time of seroconversion. Among 26 couples with a male index case, there were 4 seroconversions (15%) and among 67 female index cases there were 2 seroconversions (3%). All seroconversions occurred with virus loads >1000 copies/mL. Eight female index cases (22%) reported no condom use.
                Heterosexual transmission occurred more frequently from HIV-infected males to females (rate ratio 3.5; CI, 95% 0.8-16.5 P = 0.259), although without statistical significance, probably because of the small sample. Transmitters showed significantly higher median viral loads (P = 0.042) suggesting that heterosexual transmission of HIV is more a function of viral load than gender of index case. ARV use may play a role in the prevention of HIV-1 heterosexual transmission. Other factors may be involved and should be further evaluated in larger cohorts. To evaluate the impact of antiretroviral therapy (ART) on HIV-1 transmission rates among HIV-1 discordant couples in Rakai, Uganda.
                Observational cohort study.
                HIV-1 discordant couples were retrospectively identified between 2004 and 2009. Study participants underwent annual screening for HIV-1 and were interviewed to evaluate risk behaviors. Participants were offered voluntary counseling and testing and provided with risk reduction counseling. Free ART was offered to participants with a CD4 cell count of 250 cells/μl or less or WHO stage IV disease. HIV-1 incidence and sexual risk behaviors were compared before and after the HIV-1-positive index partners started ART.
                Two hundred and fifty HIV-1 discordant couples were followed between 2004 and 2009 and 32 HIV-1-positive partners initiated ART. Forty-two HIV-1 transmissions occurred over 459.4 person-years prior to ART initiation, incidence 9.2/100 person-years [95% confidence interval (CI) 6.59-12.36]. In 32 couples in which the HIV-1 index partners started ART, no HIV-1 transmissions occurred during 53.6 person-years. The 95% CI for the incidence rate difference was -11.91 to -6.38 (P = 0.0097). Couples reported more consistent condom use during ART use, but there was no significant difference in the number of sexual partners or other risk behaviors. Viral load was markedly reduced in persons on ART.
                HIV-1 transmission may be reduced among HIV-1 discordant couples after initiation of ART due to reductions in HIV-1 viral load and increased consistent condom use. To determine the incidence of heterosexual human immunodeficiency virus type 1 disease transmission and the effect of zidovudine therapy on this risk of transmission.
                A cohort of 436 monogamous seronegative female sexual partners of human immunodeficiency virus type 1-infected males was followed up for 740 person-years with regular structured interviews and laboratory tests.
                At enrollment of the women, 50% of their infected partners had one or more signs of disease progression (symptoms of acquired immunodeficiency syndrome, p24 antigen positivity, or CD4+ cell counts lower than 0.4 x 10(9)/L) and 15% were treated with zidovudine.
                Incidence rates of seroconversion were calculated and relative risks were estimated as incidence rate ratios.
                Twenty-seven women seroconverted during follow-up, and the incidence of seroconversion was 3.7 per 100 person-years. Seroconversion was about six times more frequent (relative risk, 5.8; 95% confidence interval, 2.2 to 15.3) in couples not using condoms. Men with signs of disease progression transmitted infection to their partners more frequently and were more frequently treated with zidovudine. When the risk of transmission was estimated accounting for disease progression, the rate of transmission in zidovudine-treated men was lower than in untreated men (relative risk, 0.5; 95% confidence interval, 0.1 to 0.9).
                Treatment of human immunodeficiency virus type-1 infected men with zidovudine reduces, but does not eliminate, heterosexual transmission of infection. Behavioral counseling that encourages sexual practices with a lower risk of transmission remains the most important method of prevention.