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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Available from: Wendy Susan Stevens, Oct 02, 2015
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    • "It is thus critical to examine the relationship between HIV transmission and treatment from multidimensional perspectives. Observational or experimental studies [10] [15] and a meta-analysis [9] demonstrated that the effectiveness of ART "
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    ABSTRACT: The preventative effects of antiretroviral therapy for people with HIV have been debated since they were first raised. Models commenced studying the preventive effects of treatment in the 1990s, prior to initial public reports. However, the outcomes of the preventive effects of antiretroviral use were not consistent. Some outcomes of dynamic models were based on unfeasible assumptions, such as no consideration of drug resistance, behavior disinhibition, or economic inputs in poor countries, and unrealistic input variables, for example, overstated initiation time, adherence, coverage, and efficacy of treatment. This paper reviewed dynamic mathematical models to ascertain the complex effects of ART on HIV transmission. This review discusses more conservative inputs and outcomes relative to antiretroviral use in HIV infections in dynamic mathematical models. ART alone cannot eliminate HIV transmission.
    12/2014; 2014:760734. DOI:10.1155/2014/760734
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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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    ABSTRACT: Background Although there is considerable evidence of the effectiveness of needle and syringe programme (NSP), opioid substitution therapy (OST) and antiretroviral therapy (ART) in reducing HIV prevalence, most Central and Eastern European sub-regions still have low or no coverage of most or all of these interventions. Methods We conducted a modelling analysis to consider the potential impact on HIV incidence and prevalence of OST, NSP and ART in three illustrative epidemic scenarios: Russia (St. Petersburg); Estonia (Tallinn) and Tajikistan (Dushanbe). For each intervention, we consider the coverage needed of each intervention separately or in combination to: (1) achieve a 30% or 50% relative reduction in HIV incidence or prevalence over 10 years; and (2) reduce HIV incidence to below 1% or HIV prevalence below 10% after 20 years. A sensitivity analysis for St. Petersburg considered the implications of greater on no risk heterogeneity, none or more sexual HIV transmission, like-with-like mixing, different injecting cessation rates and assuming a lower HIV acute phase cofactor. Results For St. Petersburg, when OST, NSP and ART are combined, only 14% coverage of each intervention is required to achieve a 30% reduction in HIV incidence over 10 years. Similar findings are obtained for Tallinn and Dushanbe. In order to achieve the same reductions in HIV prevalence over 10 years, over double the coverage level is required relative to what was required to achieve the same reduction in HIV incidence in that setting. To either reduce HIV incidence to less than 1% or HIV prevalence to less than 10% over 20 years, with all interventions combined, projections suggest that very high coverage levels of 74-85% are generally required for the higher prevalence settings of Tallinn and St. Petersburg, whereas lower coverage levels (23-34%) are needed in Dushanbe. Coverage requirements are robust to increased sexual HIV transmission, risk heterogeneity and like-with-like mixing, as well as to assuming a lower HIV acute phase cofactor or different injecting cessation rate. Conclusion The projections suggest that high but achievable coverage levels of NSP can result in large decreases (30%) in HIV incidence in settings with high HIV prevalence among PWID. Required coverage levels are much lower when interventions are combined or in lower prevalence settings. However, even when all three interventions are combined, the targets of reducing HIV incidence to less than 1% or prevalence to less than 10% in 20 years may be hard to achieve except in lower prevalence settings.
    The International journal on drug policy 11/2014; 25(6):1163–1173. DOI:10.1016/j.drugpo.2014.09.013 · 2.54 Impact Factor
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    • "ART reduces both vertical and horizontal HIV transmission risks associated with pregnancy and childbearing. Observational studies [40], [41] and a clinical trial [42] among discordant couples have shown that earlier antiretroviral therapy (ART) initiation substantially reduces the risk of HIV transmission within sero-discordant couples. ART decreases infectivity among its users by reducing their viral loads, with virtually no transmission by PLWHA with undetectable viral loads [43]. "
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    ABSTRACT: Objectives Fertility desires require new understanding in a context of expanding access to antiretroviral therapy for people living with HIV/AIDS in Sub-Saharan Africa. This paper studies the fertility desires and their rationales, of slum-dwelling Kenyan men and women living with HIV/AIDS who know their serostatus, but have different antiretroviral therapy treatment statuses. It addresses two research questions: How do people living with HIV/AIDS consider their future fertility? What factors contribute to an explanation of fertility desires among people living with HIV/AIDS. Methods A mixed methods study (survey [n = 513] and in-depth interviews [n = 41]) with adults living with HIV/AIDS living in Nairobi slums was conducted in 2010. Regression analyses assess independent relationships between fertility desires and socio-demographic factors. Analyses of in-depth interviews are used to interpret the statistical analyses of fertility desires. Results Our analyses show that fertility desires are complex and ambivalent, reflecting tensions between familial and societal pressures to have children versus pressures for HIV (re-)infection prevention. More than a third (34%) of men and women living with HIV expressed future fertility desires; however, this is significantly lower than in the general population. Factors independently associated with desiring a child among people living with HIV/AIDS were age, sex, number of surviving children, social support and household wealth of the respondent. Discussion Increasing access to ART is changing the context of future childbearing for people living with HIV/AIDS. Prevailing values mean that, for many people living with HIV/AIDS, having children is seen as necessary for a “normal” and healthy adult life. However, the social rewards of childbearing conflict with moral imperatives of HIV prevention, presenting dilemmas about the “proper” reproductive behaviour of people living with HIV/AIDS. The health policy and service delivery implications of these findings are explored.
    PLoS ONE 08/2014; 9(8):e106292. DOI:10.1371/journal.pone.0106292 · 3.23 Impact Factor
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