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      Effect of Early Antiretroviral Therapy on Sexual Behaviors and HIV-1 Transmission Risk Among Adults With Diverse Heterosexual Partnership Statuses in Côte d'Ivoire

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          Background.  The effect of early initiation of antiretroviral therapy (ART; ie, at CD4 + T-cell counts >350 cells/mm 3) on sexual behaviors and human immunodeficiency virus type 1 (HIV) transmission risk has not been documented in populations other than HIV-serodiscordant couples in stable relationships.

          Methods.  On the basis of data from a behavioral study nested in a randomized, controlled trial (Temprano-ANRS12136) of early ART, we compared proportions of risky sex (ie, unprotected sex with a partner of negative/unknown HIV status) reported 12 months after inclusion between participants randomly assigned to initiate ART immediately (hereafter, “early ART”) or according to ongoing World Health Organization criteria. Group-specific HIV transmission rates were estimated on the basis of sexual behaviors and viral load–specific per-act HIV transmission probabilities. The ratio of transmission rates was computed to estimate the protective effect of early ART.

          Results.  Among 957 participants (baseline median CD4 + T-cell count, 478 cells/mm 3), 46.0% reported sexual activity in the past month; of these 46.0%, sexual activity for 41.5% involved noncohabiting partners. The proportion of subjects who engaged in risky sex was 10.0% in the early ART group, compared with 12.8% in the standard ART group ( P = .17). After accounting for sexual behaviors and viral load, we estimated that the protective effect of early ART was 90% (95% confidence interval, 81%–95%).

          Conclusion.  Twelve months after inclusion, patients in the early and standard ART groups reported similar sexual behaviors. Early ART decreased the estimated risk of HIV transmission by 90%, suggesting a major prevention benefit among seronegative sex partners in stable or casual relationships with seropositive individuals.

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          Most cited references 37

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          Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda.

           T VanCott,  ,  Xiaohui Li (2001)
          The probability of HIV-1 transmission per coital act in representative African populations is unknown. We aimed to calculate this probability overall, and to estimate how it is affected by various factors thought to influence infectivity. 174 monogamous couples, in which one partner was HIV-1 positive, were retrospectively identified from a population cohort in Rakai, Uganda. Frequency of intercourse and reliability of reporting within couples was assessed prospectively. HIV-1 seroconversion was determined in the uninfected partners, and HIV-1 viral load was measured in the infected partners. Adjusted rate ratios of transmission per coital act were estimated by Poisson regression. Probabilities of transmission per act were estimated by log-log binomial regression for quartiles of age and HIV-1 viral load, and for symptoms or diagnoses of sexually transmitted diseases (STDs) in the HIV-1-infected partners. The mean frequency of intercourse was 8.9 per month, which declined with age and HIV-1 viral load. Members of couples reported similar frequencies of intercourse. The overall unadjusted probability of HIV-1 transmission per coital act was 0.0011 (95% CI 0.0008-0.0015). Transmission probabilities increased from 0.0001 per act at viral loads of less than 1700 copies/mL to 0.0023 per act at 38 500 copies/mL or more (p=0.002), and were 0.0041 with genital ulceration versus 0.0011 without (p=0.02). Transmission probabilities per act did not differ significantly by HIV-1 subtypes A and D, sex, STDs, or symptoms of discharge or dysuria in the HIV-1-positive partner. Higher viral load and genital ulceration are the main determinants of HIV-1 transmission per coital act in this Ugandan population.
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            Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review.

            Following large-scale roll-out of antiretroviral therapy in sub-Saharan Africa, the non-clinical efficacy of antiretroviral therapy has received little attention. We aimed to systematically review virological efficacy and drug-resistance outcomes of programmes of antiretroviral therapy in sub-Saharan Africa. 89 studies with heterogeneous design, definitions, and methods were identified. Overall, in on-treatment analysis, 10 351 (78%) of 13 288 patients showed virological suppression after 6 months of antiretroviral therapy, 7413 (76%) of 9794 after 12 months, and 3840 (67%) of 5690 after 24 months. Long-term virological data are scarce. Genotyping results were available for patients with virological failure (HIV-1 RNA greater than 1000 copies per mL). Most patients (839 of 849; 99%) were infected with a non-B HIV-1 subtype. However, drug-resistance patterns were largely similar to those in subtype B. Resistance profiles were associated with the antiretroviral drugs commonly used: the lamivudine-associated M184V mutation was most common, followed by K103N which is associated with non-nucleoside reverse transcriptase inhibitors. Thymidine-analogue mutations and the K65R mutation were less common. First-line antiretroviral therapy regimens used in sub-Saharan Africa are effective. Profiles of drug resistance suggest that a second-line treatment regimen based on protease inhibitors, with a backbone of nucleoside reverse transcriptase inhibitors, is a reasonable option for patients with HIV in sub-Saharan Africa who experience first-line treatment failure. 2010 Elsevier Ltd. All rights reserved.
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              Determinants of per-coital-act HIV-1 infectivity among African HIV-1-serodiscordant couples.

              Knowledge of factors that affect per-act infectivity of human immunodeficiency virus type 1 (HIV-1) is important for designing HIV-1 prevention interventions and for the mathematical modeling of the spread of HIV-1. We analyzed data from a prospective study of African HIV-1-serodiscordant couples. We assessed transmissions for linkage within the study partnership, based on HIV-1 sequencing. The primary exposure measure was the HIV-1-seropositive partners' reports of number of sex acts and condom use with their study partner. Of 3297 couples experiencing 86 linked HIV-1 transmissions, the unadjusted per-act risks of unprotected male-to-female (MTF) and female-to-male (FTM) transmission were 0.0019 (95% confidence interval [CI], .0010-.0037) and 0.0010 (95% CI, .00060-.0017), respectively. After adjusting for plasma HIV-1 RNA of the HIV-1-infected partner and herpes simplex virus type 2 serostatus and age of the HIV-1-uninfected partner, we calculated the relative risk (RR) for MTF versus FTM transmission to be 1.03 (P = .93). Each log(10) increase in plasma HIV-1 RNA increased the per-act risk of transmission by 2.9-fold (95% CI, 2.2-3.8). Self-reported condom use reduced the per-act risk by 78% (RR = 0.22 [95% CI, .11-.42]). Modifiable risk factors for HIV-1 transmission were plasma HIV-1 RNA level and condom use, and, in HIV-1-uninfected partners, herpes simplex virus 2 infection, genital ulcers, Trichomonas vaginalis, vaginitis or cervicitis, and male circumcision.

                Author and article information

                J Infect Dis
                J. Infect. Dis
                The Journal of Infectious Diseases
                Oxford University Press
                1 February 2014
                29 August 2013
                29 August 2013
                : 209
                : 3
                : 431-440
                [1 ]Epidemiology of Occupational and Social Determinants of Health, Center for Research in Epidemiology and Population Health, INSERM U1018
                [2 ]UMRS 1018, Université Versailles Saint-Quentin , Villejuif
                [3 ]INSERM U897, Université Bordeaux Segalen , Bordeaux
                [4 ]CEPED, UMR 196, Paris Descartes/INED/IRD, IRD , Paris, France
                [5 ]PAC-CI Program, CHU de Treichville
                [6 ]Department of Population Research and Development, National Institute of Statistics and Applied Economy
                [7 ]Service des Maladies Infectieuses et Tropicales, CHU de Treichville , Abidjan, Côte d'Ivoire, France
                Author notes

                Presented in part: 7th IAS Conference on HIV Pathogenesis, Treatment, and Prevention, Kuala Lumpur, Malaysia, 30 June–3 July 2013. Abstract MOAC0201.

                Correspondance: Kévin Jean, MSc, CESP Eq. 11, Hôp. Paul Brousse, Bât 15-16, 16 avenue Paul Vaillant Couturier, 94800 Villejuif, France ( kevin.jean@ 123456inserm.fr ).
                © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com .

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