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      Viral suppression after 12 months of antiretroviral therapy in low- and middle-income countries: a systematic review Translated title: Suppression virale après 12 mois de traitement antirétroviral dans les pays à revenu faible et intermédiaire: bilan systématique Translated title: Supresión viral tras 12 meses de terapia con antiretrovirales en países de renta baja y media: una revisión sistemática

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          Abstract

          OBJECTIVE: To establish estimates of viral suppression in low- and middle-income countries (LMICs) in patients who received antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection. METHODS: Data on viral suppression after 12 months of ART in LMICs were collected from articles published in 2003 to 2011 and from abstracts of conferences held between 2009 and 2011. Pooled proportions for on-treatment and intention-to-treat populations were used as summary estimates. Random-effects models were used for heterogeneous groups of studies (I² > 75%). FINDINGS: Overall, 49 studies covering 48 cohorts and 30 016 individuals met the inclusion criteria. With thresholds for suppression between 300 and 500 copies of viral ribonucleic acid (RNA) per ml of plasma, 84.3% (95% confidence interval, CI: 80.4-87.9) of the pooled on-treatment population and 70.5% (95% CI: 65.2-75.6) of the intention-to-treat population showed suppression. Use of different viral RNA thresholds changed the proportions showing suppression: to 84% and 76% of the on-treatment population with thresholds set above 300 and at or below 200 RNA copies per ml, respectively, and to 78%, 71% and 63% of the intention-to-treat population at thresholds set at 1000, 300 to 500, and 200 or fewer copies per ml, respectively. CONCLUSION: The pooled estimates of viral suppression recorded after 12 months of ART in LMICs provide benchmarks that other ART programmes can use to set realistic goals and perform predictive modelling. Evidence from this review suggests that the current international target - i.e. viral suppression in > 70% of the intention-to-treat population, with a threshold of 1000 copies per ml - should be revised upwards.

          Translated abstract

          OBJECTIF: Estimer la suppression virale dans les pays à revenu faible et intermédiaire (PRFI) chez des patients ayant reçu un traitement antirétroviral (TAR) contre l'infection due au virus de l'immunodéficience humaine (VIH). MÉTHODES: Des données sur la suppression virale après 12 mois de TAR dans les PRFI ont été recueillies à partir d'articles publiés entre 2003 et 2011 et de comptes rendus de conférences qui ont eu lieu entre 2009 et 2011. Comme estimations sommaires, on a utilisé des proportions globales pour les populations en cours de traitement et ayant l'intention d'être traitées. On a utilisé des modèles d'effets aléatoires pour les groupes d'études hétérogènes (I²> 75%). RÉSULTATS: Dans l'ensemble, 49 études couvrant 48 cohortes et 30 016 individus respectaient les critères d'inclusion. Avec des seuils de suppression allant de 300 à 500 copies d'acide ribonucléique (ARN) viral par ml de plasma, 84,3% (intervalle de confiance de 95%, IC: 80, 4-87,9) de la population en cours traitement analysée et 70,5% (95% IC: 65,2-75,6) de la population ayant l'intention d'être traitée indiquaient une suppression. L'utilisation de différents seuils d'ARN viral changeait les proportions montrant la suppression: à 84% et 76% de la population en cours de traitement avec des seuils fixés respectivement à plus de 300 et à 200 copies ou moins d'ARN par ml, et à 78%, 71% et 63% de la population ayant l'intention d'être traitée à des seuils fixés respectivement à 1 000, 300 à 500, et à 200 copies ou moins par ml. CONCLUSION: Les estimations globales de la suppression virale enregistrées après 12 mois de TAR dans les PRFI indiquent que d'autres programmes de TAR peuvent être utilisés pour définir des objectifs réalistes et pour créer une modélisation prédictive. Les conclusions de cette étude suggèrent que l'objectif international actuel - la suppression virale chez plus de 70% des personnes qui ont l'intention de se soigner, avec un seuil de 1 000 copies par ml - devrait être revu à la hausse.

          Translated abstract

          OBJETIVO: Calcular la supresión viral en países de renta baja y media (PRBM) en pacientes que recibieron terapia con antiretrovirales (TAR) para tratar la infección por el virus de inmunodeficiencia humana (VIH). MÉTODOS: Se recabaron datos sobre la supresión viral tras 12 meses de TAR basados en artículos publicados entre 2003 y 2011, así como en resúmenes de conferencias que tuvieron lugar entre 2009 y 2011. Se emplearon proporciones combinadas entre poblaciones en tratamiento y con intención de tratar como estimaciones globales. Se usaron modelos de efectos aleatorios para grupos de estudio heterogéneos (I²> 75%). RESULTADOS: En líneas generales, 49 estudios que incluían 48 cohortes y 30 016 individuos cumplieron los criterios de inclusión. El 84,3% (intervalo de confianza del 95%, IC: 80,4-87,9) del conjunto de la población en tratamiento y el 70,5% (IC del 95%: 65,2-75,6) de la población con intención de tratar mostraron supresión con umbrales para la supresión de entre 300 y 500 copias de ácido ribonucleico viral (RNA) por ml de plasma. El empleo de diferentes umbrales virales RNA cambió las proporciones que indican supresión: al 84% y 76% de la población en tratamiento con umbrales superiores a 300 y a o por debajo de 200 copias de RNA por ml, respectivamente, y a 78%, 71% y 63% de la población con intención de tratar con umbrales fijados en 1000, 300 a 500 y 200 o menos copias por ml, respectivamente. CONCLUSIÓN: Las estimaciones combinadas de supresión viral que se registraron tras 12 meses de TAR en PRBM establecen que pueden emplearse otros programas TAR para establecer objetivos realistas y realizar modelos de predicción. Las constataciones de esta revisión sugieren que el objetivo internacional en la actualidad - es decir, la supresión viral en > 70% de la población con intención de tratar, con un umbral de 1000 copias por ml - debe revisarse al alza.

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          Antiretroviral therapy adherence, virologic and immunologic outcomes in adolescents compared with adults in southern Africa.

          To determine adherence to and effectiveness of antiretroviral therapy (ART) in adolescents vs. adults in southern Africa. Observational cohort study. Aid for AIDS, a private sector disease management program in southern Africa. Adolescents (age 11-19 years; n = 154) and adults (n = 7622) initiating ART between 1999 and 2006 and having a viral load measurement within 1 year after ART initiation. Primary: virologic suppression (HIV viral load < or = 400 copies/mL), viral rebound, and CD4 T-cell count at 6, 12, 18, and 24 months after ART initiation. Secondary: adherence assessed by pharmacy refills at 6, 12, and 24 months. Multivariate analyses: loglinear regression and Cox proportional hazards. A significantly smaller proportion of adolescents achieved 100% adherence at each time point (adolescents: 20.7% at 6 months, 14.3% at 12 months, and 6.6% at 24 months; adults: 40.5%, 27.9%, and 20.6% at each time point, respectively; P < 0.01). Patients achieving 100% 12-month adherence were significantly more likely to exhibit virologic suppression at 12 months, regardless of age. However, adolescents achieving virologic suppression had significantly shorter time to viral rebound (adjusted hazard ratio 2.03; 95% confidence interval: 1.31 to 3.13; P < 0.003). Adolescents were less likely to experience long-term immunologic recovery despite initial CD4 T-cell counts comparable to adults. Compared with adults, adolescents in southern Africa are less adherent to ART and have lower rates of virologic suppression and immunologic recovery and a higher rate of virologic rebound after initial suppression. Studies must determine specific barriers to adherence in this population and develop appropriate interventions.
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            Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel.

            Recent data regarding the consequences of untreated human immunodeficiency virus (HIV) infection and the expansion of treatment choices for antiretroviral-naive and antiretroviral-experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adults with HIV infection. To provide updated recommendations for management of HIV-infected adults, using antiretroviral drugs and laboratory monitoring tools available in the international, developed-world setting. This report provides guidelines for when to initiate antiretroviral therapy, selection of appropriate initial regimens, patient monitoring, when to change therapy, and what regimens to use when changing. A panel with expertise in HIV research and clinical care reviewed relevant data published or presented at selected scientific conferences since the last panel report through April 2010. Data were identified through a PubMed search, review of scientific conference abstracts, and requests to antiretroviral drug manufacturers for updated clinical trials and adverse event data. New evidence was reviewed by the panel. Recommendations were drafted by section writing committees and reviewed and edited by the entire panel. The quality and strength of the evidence were rated and recommendations were made by full panel consensus. Patient readiness for treatment should be confirmed before initiation of antiretroviral treatment. Therapy is recommended for asymptomatic patients with a CD4 cell count 500/microL. Components of the initial and subsequent regimens must be individualized, particularly in the context of concurrent conditions. Patients receiving antiretroviral treatment should be monitored regularly; treatment failure should be detected and managed early, with the goal of therapy, even in heavily pretreated patients, being HIV-1 RNA suppression below commercially available assay quantification limits.
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              Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment.

              The recording of outcomes from large-scale, simplified HAART (highly active antiretroviral therapy) programmes in sub-Saharan Africa is critical. We aimed to assess the effectiveness of such a programme held by Médecins Sans Frontières (MSF) in the Chiradzulu district, Malawi. We scaled up and simplified HAART in this programme since August, 2002. We analysed survival indicators, CD4 count evolution, virological response, and adherence to treatment. We included adults who all started HAART 6 months or more before the analysis. HIV-1 RNA plasma viral load and self-reported adherence were assessed on a subsample of patients, and antiretroviral resistance mutations were analysed in plasma with viral loads greater than 1000 copies per mL. Analysis was by intention to treat. Of the 1308 patients who were eligible, 827 (64%) were female, the median age was 34.9 years (IQR 29.9-41.0), and 1023 (78%) received d4T/3TC/NVP (stavudine, lamivudine, and nevirapine) as a fixed-dose combination. At baseline, 1266 individuals (97%) were HAART-naive, 357 (27%) were at WHO stage IV, 311 (33%) had a body-mass index of less than 18.5 kg/m2, and 208 (21%) had a CD4 count lower than 50 cells per muL. At follow-up (median 8.3 months, IQR 5.5-13.1), 967 (74%) were still on HAART, 243 (19%) had died, 91 (7%) were lost to follow-up, and seven (0.5%) discontinued treatment. Low body-mass index, WHO stage IV, male sex, and baseline CD4 count lower than 50 cells per muL were independent determinants of death in the first 6 months. At 12 months, the probability of individuals still in care was 0.76 (95% CI 0.73-0.78) and the median CD4 gain was 165 (IQR 67-259) cells per muL. In the cross-sectional survey (n=398), 334 (84%) had a viral load of less than 400 copies per mL. Of several indicators measuring adherence, self-reported poor adherence (<80%) in the past 4 days was the best predictor of detectable viral load (odds ratio 5.4, 95% CI 1.9-15.6). These data show that large numbers of people can rapidly benefit from antiretroviral therapy in rural resource-poor settings and strongly supports the implementation of such large-scale simplified programmes in Africa.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                bwho
                Bulletin of the World Health Organization
                Bull World Health Organ
                World Health Organization (Genebra )
                0042-9686
                May 2013
                : 91
                : 5
                : 377-385
                Affiliations
                [1 ] Alfred Hospital Australia
                [2 ] World Health Organization Switzerland
                [3 ] Tufts University USA
                Article
                S0042-96862013000500013
                10.2471/BLT.12.112946
                3646348
                23678201
                03323ea4-bf9a-4d15-8931-4af12b1d0b20

                http://creativecommons.org/licenses/by/4.0/

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                SciELO Public Health

                Self URI (journal page): http://www.scielosp.org/scielo.php?script=sci_serial&pid=0042-9686&lng=en
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                Health Policy & Services

                Public health
                Public health

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