Suppression virale après 12 mois de traitement antirétroviral dans les pays à revenu faible et intermédiaire: bilan systématique
Supresión viral tras 12 meses de terapia con antiretrovirales en países de renta baja y media: una revisión sistemática
James H McMahonI,*; Julian H ElliottI; Silvia BertagnolioII; Rachel KubiakIII; Michael R JordanIII
IInfectious Diseases Unit, Alfred Hospital, Level 2 Burnet Tower, 85 Commercial Road, Melbourne, 3004, Australia
IIHIV Department, World Health Organization, Geneva, Switzerland
IIIDepartment of Public Health and Community Medicine, Tufts University School of Medicine, Boston, United States of America
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: 80.487.9) of the pooled on-treatment population and 70.5% (95% CI: 65.275.6) 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.
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, 487,9) de la population en cours traitement analysée et 70,5% (95% IC: 65,275,6) 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.
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: 80,487,9) del conjunto de la población en tratamiento y el 70,5% (IC del 95%: 65,275,6) 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.
At the end of 2011, over 8 million people in low- and middle-income countries (LMICs) were receiving antiretroviral therapy (ART).1 The guidelines of the World Health Organization (WHO) for the treatment of human immunodeficiency virus (HIV) infection recommend that, where possible, the viral loads of individuals receiving ART be measured every 6 months to detect viral replication and confirm treatment failure whenever it occurs.2 Although viral load tests are currently too costly for routine use in many LMICs, the potential for increased access to such tests exists as costs decrease and countries prioritize this method of patient monitoring.3
WHO's guidelines for the treatment of HIV infection recommend that a viral load of > 5000 copies of viral ribonucleic acid (RNA) per ml be taken as indicative of virological failure.2 According to WHO's strategy for the surveillance and monitoring of HIV drug resistance in LMICs, a viral load of < 1000 RNA copies per ml should be taken as evidence of viral suppression.4 Guidelines for the treatment of HIV infection in high-income countries stipulate that a viral load of < 50 RNA copies per ml or a load below the limit of detection of the most sensitive assay available be taken as evidence of viral suppression,57 and that a load of > 50 RNA copies per ml,5,7 or one of > 200 viral RNA copies per ml confirmed by repeat testing,6 be used as evidence of virological failure or rebound.
The proportion of a study cohort showing viral suppression is calculated as the number of patients with viral suppression divided either by the number of patients in the study cohort who began ART (i.e. the intention-to-treat population), or by the number of patients in the cohort who are alive and on treatment (i.e. the on-treatment population). On-treatment analyses reflect the effectiveness of ART for those receiving antiretroviral drugs. Intention-to-treat analyses, which use a denominator that includes individuals who die or are lost to follow-up during the study period, reflect factors at the individual or programme level that influence the risk of death and disengagement from care. Relatively high mortality in the first 6 to 12 months of ART and substantial loss to follow-up, both of which have been widely reported in LMICs, can therefore influence estimates of viral suppression based on intention to treat.8,9
Summary estimates of viral suppression (as measured, for example, 12 months after ART initiation) are needed to guide ART programme managers on the normative levels of population-level viral suppression and to define desirable levels of clinic and programme performance. Such estimates are also useful when creating and improving mathematical models of the different strategies that might be followed to provide ART in LMICs. Recent reviews of virological outcomes have focused on sub-Saharan Africa and levels of acquired resistance to antiretroviral drugs.10,11 Across LMICs, summary estimates of viral suppression based on different HIV-RNA thresholds are lacking. The objective of this systematic review was to establish estimates, based on different viral RNA thresholds, of the percentages of the intention-to-treat and on-treatment populations in LMICs that show viral suppression 12 months after ART initiation.
We included publications ("papers") or conference abstracts that reported the proportion of individuals in a study cohort from an LMIC for whom a virological outcome after 12 months of ART was reported, either as a primary or a secondary finding. If only the median duration of follow-up was reported for a study, that study was included in the review provided the median duration was between 9 and 15 months. Any definition of viral suppression (or failure) reporting a proportion of patients below (or above) a defined viral RNA threshold was accepted. If the threshold was not reported, the relevant authors were contacted and asked for details of the threshold that they had used. A study was excluded if (i) the threshold used could not be determined; (ii) only changes in viral RNA loads from the baseline values were reported; (iii) most of the patients were less than 13 years old; (iv) patients received only one or two antiretroviral drugs; or (v) the study was not from an LMIC. All the studies included in the review were published in English and were either clinical trials or cross-sectional or cohort in design.
We searched for relevant articles published between 1 January 2003 and 31 May 2011 through Ovid MEDLINE. Online databases containing the abstracts of presentations made at the International AIDS Society Conferences held in 20092010 and at the Conferences on Retroviruses and Opportunistic Infections held in 20092011 were also searched.12,13
Our search strategy combined the relevant medical subject headings (MeSH) with additional search terms to identify those studies that reported virological outcomes for HIV-infected participants receiving ART. We used other MeSH and search terms to identify studies from LMICs in which outcomes after 12 months of ART were investigated. When more than one article reported data from the same cohort of patients and used the same viral RNA threshold, only the article that contained the most detailed information was selected. Fig. 1 summarizes the search strategy and study selection process. The study protocol provides further details.14
The following data were abstracted from each study: first author, year of publication, study country or countries, health-care setting (i.e. public sector, private sector or nongovernmental organization), whether the study patients had to pay for their ART, dates the patients were observed, number of study sites, number of patients receiving ART, baseline demographics (i.e. age, gender, CD4+ T-lymphocyte count and clinical stage), ART regimen, whether patients were ART-naive at baseline, study definition of virological outcome, and the proportion of patients meeting that definition 12 months after initiating ART. When available, the percentages of subjects who died, transferred out, stopped ART or were lost to follow-up were also abstracted. Whether the proportion of the study cohort reported to have viral suppression was based on an on-treatment or intention-to treat analysis was noted. If intention-to-treat values had not been reported, they were calculated from the raw data (when available). In these calculations, the number of patients who had died or been lost to follow-up at the time of the estimation of virological outcome and, when available, the number that had stopped ART were included in the denominator. Patients who transferred out of the study cohort were excluded from the denominator, consistent with the indicators of retention in care recommended by WHO and the United States President's Emergency Plan for AIDS Relief (PEPFAR).1518 If only the fraction of patients showing virological failure was reported, we calculated from this figure the proportion with viral suppression.
Proportions (%) of patients meeting the study definition of viral suppression were derived from text, tables or, if they could be accurately determined or estimated in this manner, from published graphs. Summary estimates were determined and categorized as on-treatment or intention-to-treat values. We assessed heterogeneity among proportions by calculating the I2 statistic. If heterogeneity was high (I2 > 75%), we pooled proportions using the FreemanTukey method with a random-effects model and DerSimonianLaird weights.19,20 When possible, we determined summary estimates of viral suppression using different threshold ranges for viral RNA: > 1000, 300500 and/or < 200 copies per ml. Additionally, we calculated summary estimates separately for studies in which one or two viral load tests were used per patient to define virological outcomes. We performed subgroup analyses to examine the influence of the year of ART initiation and of the time taken to publish the research findings (i.e. the "time-lag bias") on the summary estimates for the on-treatment populations. Year of ART initiation was defined as the median year of ART initiation and reported as pre-2004, 20042005 or post-2005. The time from the median year of ART initiation until publication was categorized as < 3, 4 or > 5 years. Analyses were conducted using Excel (Microsoft, Redmond, United States of America) and version 2.7.9 of the StatsDirect software package (StatsDirect, Altrincham, United Kingdom of Great Britain and Northern Ireland).
Overall, 49 studies (38 papers2158 and 11 conference abstracts5969), together comprising 48 cohorts and 30 016 individuals, were identified for inclusion ( Fig. 1 ). Details of the cohorts from the papers and conference abstracts are presented in Table 1 and Table 2 (available at: http://www.who.int/bulletin/volumes/90/5/12-112946), respectively. Two reports29,52 described outcomes from the same cohort but made use of two different thresholds to define viral suppression. A further seven reports26,27,43,44,47,53,55 described outcomes using two or more thresholds of viral suppression. The data from another two papers24,25 were combined to obtain an estimate of viral suppression in a single cohort. The 48 cohorts in the systematic review comprised 43 single-country cohorts 37 from sub-Saharan Africa, 3 from Asia and 3 from Latin America or the Caribbean and 5 multi-country cohorts (of which 4 were from sub-Saharan Africa).
All but one study68 used a single viral load measurement per patient to define the virological outcome. The ART regimens used were reported for 39 of the studies. In each of 35 (90%) and 29 (74%) of these studies, at least 50% and 95% of the patients, respectively, had received a regimen based on a non-nucleoside reverse-transcriptase inhibitor (NNRTI). Most of the patients in another three studies a clinical trial studying the efficacy of boosted protease-inhibitor regimens26 and two studies from regions with high prevalences of HIV-2 infection35,45 had received regimens based on a protease inhibitor.
Summary estimates from on-treatment and intention-to-treat analyses are presented for those studies in which outcomes were defined using a single viral load measurement in Table 3 and Fig. 2 . As high levels of heterogeneity were observed (I2 > 90%), all summary estimates and 95% confidence intervals (CI) were calculated using a random-effects model.
The summary estimate of the proportion of patients showing viral suppression, for all viral load thresholds in 43 on-treatment analyses, was 84.0% (95% CI: 81.386.6; n = 26 599). For the nine cohorts in which viral suppression was defined as < 1000 viral RNA copies per ml, 83.5% (95% CI: 77.888.4; n = 3192) of the combined on-treatment populations showed suppression. Thresholds ranging from 300 to 500 copies per ml were used for 32 cohorts (a threshold of 400 copies per ml was used for 27 cohorts) and 84.3% (95% CI: 80.487.9; n = 25 708) of the combined on-treatment populations of these 32 cohorts showed suppression. The reported outcomes for nine and six cohorts were based on thresholds set at or below 200 and at or below 50 viral RNA copies per ml, respectively. When thresholds set at or below 200 copies per ml were used, 76.1% (95% CI: 66.884.3; n = 2167) of the combined on-treatment populations showed suppression.
The summary estimate of viral suppression for all 27 cohorts (n = 13 134) in intention-to-treat analyses was 71.2% (95% CI: 66.575.7). The corresponding value for the four analyses in which a threshold of 1000 copies per ml was used was 77.5% (95% CI: 67.686.1; n = 1201). In intention-to-treat analyses of the data from 21 and 19 cohorts, thresholds of 300500 and 400 copies per ml, respectively, were used. With thresholds that ranged from 300 to 500 copies per ml, 70.5% (95% CI: 65.275.6; n = 11 528) of the combined intention-to-treat populations showed viral suppression. Six studies reported the results of intention-to treat analyses based on thresholds set at or below 200 copies per ml four studies used a threshold set at or below 50 copies per ml and these produced a summary estimate for the frequency of viral suppression of 62.9% (95% CI: 51.273.8; n = 1654).
To investigate possible sources of heterogeneity, we performed subgroup analyses exploring the median time of ART initiation and the potential bias introduced by the time taken to publish results: the I2 values for the subgroups considered were all > 90%. When the median year of ART initiation was pre-2004, 20042005 and post-2005, the on-treatment estimates of suppression after 12 months of ART were 80.9% (95% CI: 73.087.7), 84.1% (95% CI: 78.389.2) and 84.3% (95% CI: 80.088.2), respectively. The corresponding values for delays of < 3, 4 and > 5 years between the median year of ART initiation and the year of the publication of results were similar: 83.3% (95% CI: 78.088.0), 84.0% (95% CI: 78.788.6) and 83.0% (95% CI: 76.988.3), respectively.
This is the first systematic review to quantify population-level viral suppression 12 months after ART initiation in LMICs, and to stratify estimates by viral RNA thresholds in on-treatment and intention-to-treat analyses. Over 70% of the cohorts included in the review were investigated using thresholds ranging from 300 to 500 viral RNA copies per ml and, after 12 months of ART, viral suppression was noted in 84% (on-treatment) or 71% of patients (intention-to-treat). These summary estimates compare favourably with outcomes reported in high-income countries after 12 months of NNRTI-based ART, such as the 5873% viral suppression seen in intention-to-treat analyses in early clinical trials and in a meta-analysis at thresholds set from 400 to 500 viral RNA copies per ml.7072 Observational data from Canada, the United Kingdom and the United States of America also indicate similar frequencies of viral suppression after 12 months of ART. For example, when a viral load threshold of 50 copies per ml was used, 82% of an on-treatment population investigated in the United Kingdom showed viral suppression.73 In Canada and the United States, in on-treatment analyses based on suppression thresholds between 500 and 1000 copies per ml, 6063% of individuals initiating ART when they had CD4+ T-lymphocyte counts of < 200 cells per µl were found to have attained viral suppression 12 months later.74,75
As anticipated, summary estimates for viral suppression were found to be higher in the on-treatment analyses than in the intention-to-treat analyses and to increase as the viral RNA thresholds used to define suppression increased. Individuals who are lost to follow-up in studies on the efficacy of ART and included in intention-to-treat analyses but excluded from on-treatment analyses are defined as not having achieved viral suppression. In addition, as the viral load thresholds for suppression are increased, increasing numbers of patients with low-level viraemia are categorized as cases of viral suppression.
We found no evidence of studies in LMICs that had used viral load thresholds of 10 000 or 5000 copies per ml as recommended in the ART guidelines published by WHO in 20062 and 2010,76 respectively to define viral suppression. The reasons for this are unclear. Investigators in LMICs may simply have preferred to use the lower thresholds supported either by the national ART guidelines used in the country where the study was performed or by guidelines not specifically intended for use in a public health model of care.57 They may also have wished to use thresholds based on the lower limit of sensitivity of the viral load assay that they had available.
Only one study68 reported the frequency of viral suppression based on two viral load measurements per patient. In this case, use of a second test increased the percentage of patients showing viral suppression. A second test is particularly likely to increase the percentage of patients who are virologically suppressed if an intervention to improve adherence to ART occurs after an initial detectable viral load, in a strategy that is recommended by WHO2 and already followed in several LMICs.33,77,78 Given that the overwhelming majority of reported outcomes are based on a single viral load measurement per patient, efforts to understand and summarize virological outcomes in LMICs should also be based on a single test result for each patient.
As far as possible, this review used intention-to-treat estimates of viral suppression that, as recommended in the relevant international guidelines,1518 excluded individuals who transferred out of the included studies. Individuals were reported to have transferred out of only six cohorts included in the review and, in each case, such individuals were excluded from the intention-to-treat estimate of viral suppression.21,24,25,38,46,48,49 However, only two of the reports included in the review specifically stated that no patient had transferred out.44,53 For the other 19 cohorts with intention-to-treat estimates of viral suppression, no data on transfers out were presented. This lack of data left it unclear whether any patients had transferred out and, if so, whether such patients had been incorporated in the denominator used in the final analyses. If any patients who did transfer out were unreported and still included in the denominators used in the final analyses, the intention-to-treat summary estimates generated in this review may be too low.
The summary estimates presented in this systematic review are important for target-setting and benchmarking. They provide guidance to ART clinics and programmes on the mean rates of viral suppression achieved in LMICs (normative referencing). The managers of ART programmes may define adequate levels of programme performance as those that lead to levels of viral suppression that match or exceed the summary estimates (criterion referencing).79 A combination of normative and criterion referencing methods, incorporating the data summarized in this review, may be used to categorize poor, intermediate and optimal levels of performance. In its strategy for the surveillance and monitoring of resistance to antiretrovirals, WHO recommends that ART treatment sites achieve viral suppression (as indicated by a viral load of < 1000 copies per ml) in at least 70% of the intention-to-treat population after 12 months of ART.80 Although data from this review are limited, this target should probably be increased since, in the four reviewed studies that used the same viral load threshold (n = 1201), 78% of the intention-to-treat population achieved suppression. Although detectable viral RNA after ART does not prove the presence of resistance to antiretrovirals, individuals who are virologically suppressed on ART have no effective drug resistance. Detectable viral RNA in populations receiving ART is often associated with suboptimal adherence to ART, which is predictive of the emergence of drug-resistant strains of the virus.65
The estimates presented in this review may not be truly representative, despite being mean or normative levels of viral suppression. For example, ART programmes or clinics that evaluated and reported viral loads may have greater resources and better clinical outcomes than those where viral loads were not evaluated and/or where virological outcomes were not reported. Additionally, in settings where viral loads were evaluated but where poor virological outcomes were observed, researchers may have chosen not to disseminate the results, and this may have led to publication bias. The summary estimates may therefore overestimate the mean frequency of viral suppression in the broader population receiving ART in LMICs. In addition, high levels of statistical heterogeneity (I2 > 90%) were observed during the review. Analyses that focused on year of ART initiation and the delays between the recording and publishing of results revealed persistent heterogeneity but no major differences in the proportions achieving viral suppression between the subgroups considered. These findings suggest that other, unidentified factors are potentially contributing to the between-study variation seen in the proportions of viral suppression. Despite these limitations, the systematic method used to identify studies and the statistical methods used to generate summary estimates allow for a reliable estimate of viral suppression rates based on the data available from LMICs. Another potential limitation of the present review is that most of the data investigated came from studies that used thresholds between 300 and 500 copies per ml. Relatively few results from studies based on thresholds set at 1000 or at or below 200 viral RNA copies per ml were available. In the on-treatment analyses, the summary estimate of suppression seen with a threshold of 1000 copies per ml was similar to that seen with thresholds in the range of 300 to 500 copies per ml. However, only nine cohorts were included in the calculation of viral suppression at the high threshold (n = 3192), whereas 32 cohorts (n = 25 708) were included in the calculation at the lower thresholds. The summary estimates established at 1000 copies per ml may have been too underpowered to demonstrate a difference with the estimates established at thresholds between 300 and 500 copies per ml.
In conclusion, this is the first systematic review of viral-suppression rates from LMICs after 12 months of ART. It includes summary estimates, at multiple HIV RNA thresholds, based on both on-treatment and intention-to-treat analyses. At the most commonly reported viral RNA thresholds (i.e. 300500 copies per ml), approximately 71% of the patients in the intention-to-treat analyses and 84% of those in the on-treatment analyses had attained viral suppression 12 months after ART initiation. These proportions compare favourably with outcomes observed in high-income countries and represent a substantial achievement for LMICs, where ART is generally provided under great resource constraints.
The data reported in this review have important public health implications. Researchers and managers of ART programmes in LMICs could use these results to support mathematical models of the effects of ART and set rates of viral suppression as performance targets. Use of these targets would help identify those ART clinics with suboptimal performance that would most benefit from focused interventions to improve service delivery and patient outcomes.
The authors alone are responsible for the views expressed in this publication, which do not necessarily represent the decisions or stated policies of the World Health Organization. JHM has a dual appointment with the Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, USA. JHE has dual appointments with the Department of Medicine, Monash University, Melbourne, Australia and the Burnet Institute, Melbourne, Australia. MRJ has a dual appointment with the Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, USA.
Funding: The authors received support via a Postgraduate Scholarship from the Australian National Health and Medical Research Council (JHM) and from the United States National Institutes of Health 5K23AI074423-04 (MRJ.)
Competing interests: None declared.
1. Together we will end AIDS. Geneva: Joint United Nations Programme on HIV/AIDS; 2012.
2. Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach. 2010 revision. Geneva: World Health Organization; 2010.
3. Hamers RL, Kityo C, Lange JM, de Wit TF, Mugyenyi P. Global threat from drug resistant HIV in sub-Saharan Africa. BMJ 2012;344:e4159. doi: http://dx.doi.org/10.1136/bmj.e4159 PMID: 22709963
4. Bennett DE, Bertagnolio S, Sutherland D, Gilks CF. The World Health Organization's global strategy for prevention and assessment of HIV drug resistance. Antivir Ther 2008;13(Suppl 2):113. PMID: 18578063
5. Thompson MA, Aberg JA, Cahn P, Montaner JS, Rizzardini G, Telenti A et al.; International AIDS Society-USA. Antiretroviral treatment of adult HIV infection: 2010. Recommendations of the International AIDS Society-USA panel. JAMA 2010;304:32133. doi: http://dx.doi.org/10.1001/jama.2010.1004 PMID: 20639566
6. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Washington: Department of Health and Human Services; 2012. Available from: http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf [accessed 12 May 2012] .
7. Asboe D, Aitken C, Boffito M, Booth C, Cane P, Fakoya A et al.; BHIVA Guidelines Subcommittee. British HIV Association guidelines for the routine investigation and monitoring of adult HIV-1-infected individuals 2011. HIV Med 2012;13:144. doi: http://dx.doi.org/10.1111/j.1468-1293.2011.00971.x PMID: 22171742
8. Fox MP, Rosen S. Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 20072009: systematic review. Trop Med Int Health 2010;15(Suppl 1):115. doi: http://dx.doi.org/10.1111/j.1365-3156.2010.02508.x PMID: 20586956
9. Braitstein P, Brinkhof MW, Dabis F, Schechter M, Boulle A, Miotti P et al.; Antiretroviral Therapy in Lower Income Countries (ART-LINC) Collaboration; ART Cohort Collaboration (ART-CC) groups. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet 2006;367:81724. doi: http://dx.doi.org/10.1016/S0140-6736(06)68337-2 PMID: 16530575
10. Barth RE, van der Loeff MF, Schuurman R, Hoepelman AI, Wensing AM. Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review. Lancet Infect Dis 2010;10:15566. doi: http://dx.doi.org/10.1016/S1473-3099(09)70328-7 PMID: 20185094
11. Gupta RK, Hill A, Sawyer AW, Cozzi-Lepri A, von Wyl V, Yerly S et al. Virological monitoring and resistance to first-line highly active antiretroviral therapy in adults infected with HIV-1 treated under WHO guidelines: a systematic review and meta-analysis. Lancet Infect Dis 2009;9:40917. doi: http://dx.doi.org/10.1016/S1473-3099(09)70136-7 PMID: 19555900
12. International AIDS Society [Internet]. Abstract search. Geneva: IAS; 2012. Available from: http://www.iasociety.org/AbstractSearch.aspx [accessed 12 February 2013] .
13. 18th Conference on Retroviruses and Opportunistic Infections [Internet]. Search abstracts. Boston: CROI; 2011. Available from: http://retroconference.org/AbstractSearch/Default.aspx?Conf=20 [accessed 12 February 2013] .
14. McMahon JH, Elliott JH, Bertagnolio S, Kubiak R, Jordan M. Protocol for the systematic review of virological outcomes after 12 months of antiretroviral therapy in low and middle income countries. York: University of York; 2011. Available from: http://www.crd.york.ac.uk/PROSPEROFILES/3867_STRATEGY_20130114.pdf [accessed 19 February 2013] .
15. Monitoring the Declaration of Commitment on HIV/AIDS: guidelines on construction of core indicators: 2010 reporting. Geneva: Joint United Nations Programme on HIV/AIDS; 2009.
16. Next generation indicator reference guide, version 1.1: the President's Emergency Plan for AIDS Relief. Washington: US Department of Health and Human Services; 2009.
17. Monitoring and evaluation toolkit. 4th ed. Geneva: Global Fund to Fight AIDS, Tuberculosis and Malaria; 2011.
18. A guide on indicators for monitoring and reporting on the health sector response to HIV/AIDS. Geneva: World Health Organization; 2011.
19. DerSimonian R, Laird N. Meta-analysis in clinical trials Control Clin Trials 1986;7:17788. doi: http://dx.doi.org/10.1016/j.trstmh.2008.11.007 PMID: 19110288
20. Stuart A, Ord JK. Kendall's advanced theory of statistics. 6th ed. London: Edward Arnold; 1994.
21. Ahoua L, Guenther G, Pinoges L, Anguzu P, Chaix ML, Le Tiec C et al. Risk factors for virological failure and subtherapeutic antiretroviral drug concentrations in HIV-positive adults treated in rural northwestern Uganda. BMC Infect Dis 2009;9:81. doi: http://dx.doi.org/10.1186/1471-2334-9-81 PMID: 19493344
22. Keiser O, Orrell C, Egger M, Wood R, Brinkhof MW, Furrer H et al. Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared PLoS Med 2008;5:e148. doi: http://dx.doi.org/10.1186/1471-2334-9-81 PMID: 19493344
23. Orrell C, Bangsberg DR, Badri M, Wood R. Adherence is not a barrier to successful antiretroviral therapy in South Africa. AIDS 2003;17:136975. doi: http://dx.doi.org/10.1097/00002030-200306130-00011 PMID: 12799558
24. Wouters E, Van Damme W, Van Loon F, van Rensburg D, Meulemans H. Public-sector ART in the Free State Province, South Africa: community support as an important determinant of outcome. Soc Sci Med 2009;69:117785. doi: http://dx.doi.org/10.1016/j.socscimed.2009.07.034 PMID: 19692165
25. Wouters E, Van Damme W, van Rensburg D, Meulemans H. Impact of baseline health and community support on antiretroviral treatment outcomes in HIV patients in South Africa. AIDS 2008;22:25458. doi: http://dx.doi.org/10.1097/QAD.0b013e32831c5562 PMID: 19005281
26. Ananworanich J, Gayet-Ageron A, Ruxrungtham K, Chetchotisakd P, Prasithsirikul W, Kiertiburanakul S et al.; Staccato Thailand Study Group. Long-term efficacy and safety of first-line therapy with once-daily saquinavir/ritonavir. Antivir Ther 2008;13:37580. PMID: 18572750
27. Barth RE, van der Meer JT, Hoepelman AI, Schrooders PA, van de Vijver DA, Geelen SP et al. Effectiveness of highly active antiretroviral therapy administered by general practitioners in rural South Africa. Eur J Clin Microbiol Infect Dis 2008;27:97784. doi: http://dx.doi.org/10.1007/s10096-008-0534-2 PMID: 18629557
28. Bedelu M, Ford N, Hilderbrand K, Reuter H. Implementing antiretroviral therapy in rural communities: the Lusikisiki model of decentralized HIV/AIDS care. J Infect Dis 2007;196(Suppl 3):S4648. doi: http://dx.doi.org/10.1086/521114 PMID: 18181695
29. Bisson GP, Gross R, Bellamy S, Chittams J, Hislop M, Regensberg L et al. Pharmacy refill adherence compared with CD4 count changes for monitoring HIV-infected adults on antiretroviral therapy PLoS Med 2008;5:e109. doi: http://dx.doi.org/10.1186/1471-2334-9-81 PMID: 19493344
30. Blacher RJ, Muiruri P, Njobvu L, Mutsotso W, Potter D, Ong'ech J et al. How late is too late? Timeliness to scheduled visits as an antiretroviral therapy adherence measure in Nairobi, Kenya and Lusaka, Zambia. AIDS Care 2010;22:132331. doi: http://dx.doi.org/10.1080/09540121003692235 PMID: 20711886
31. Bourgeois A, Laurent C, Mougnutou R, Nkoué N, Lactuock B, Ciaffi L et al. Field assessment of generic antiretroviral drugs: a prospective cohort study in Cameroon. Antivir Ther 2005;10:33541. PMID: 15865228
32. Bussmann H, Wester CW, Ndwapi N, Grundmann N, Gaolathe T, Puvimanasinghe J et al. Five-year outcomes of initial patients treated in Botswana's National Antiretroviral Treatment Program. AIDS 2008;22:230311. doi: http://dx.doi.org/10.1097/QAD.0b013e3283129db0 PMID: 18981769
33. Bussmann H, Wester CW, Thomas A, Novitsky V, Okezie R, Muzenda T et al. Response to zidovudine/didanosine-containing combination antiretroviral therapy among HIV-1 subtype C-infected adults in Botswana: two-year outcomes from a randomized clinical trial. J Acquir Immune Defic Syndr 2009;51:3746. doi: http://dx.doi.org/10.1097/QAI.0b013e31819ff102 PMID: 19282782
34. Charles M, Noel F, Leger P, Severe P, Riviere C, Beauharnais CA et al. Survival, plasma HIV-1 RNA concentrations and drug resistance in HIV-1-infected Haitian adolescents and young adults on antiretrovirals. Bull World Health Organ 2008;86:9707. doi: http://dx.doi.org/10.2471/BLT.07.050120 PMID: 19142298
35. Djomand G, Roels T, Ellerbrock T, Hanson D, Diomande F, Monga B et al. Virologic and immunologic outcomes and programmatic challenges of an antiretroviral treatment pilot project in Abidjan, Côte d'Ivoire. AIDS 2003;17(Suppl 3):S515. doi: http://dx.doi.org/10.1097/00002030-200317003-00002 PMID: 14565604
36. Fatti G, Grimwood A, Bock P. Better antiretroviral therapy outcomes at primary healthcare facilities: an evaluation of three tiers of ART services in four South African provinces. PLoS One 2010;5:e12888. doi: http://dx.doi.org/10.1371/journal.pone.0012888 PMID: 20877631
37. Ferradini L, Jeannin A, Pinoges L, Izopet J, Odhiambo D, Mankhambo L et al. Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment. Lancet 2006;367:133542. doi: http://dx.doi.org/10.1016/S0140-6736(06)68580-2 PMID: 16631912
38. Fielding KL, Charalambous S, Stenson AL, Pemba LF, Martin DJ, Wood R et al. Risk factors for poor virological outcome at 12 months in a workplace-based antiretroviral therapy programme in South Africa: a cohort study. BMC Infect Dis 2008;8:93. doi: http://dx.doi.org/10.1186/1471-2334-8-93 PMID: 18631397
39. Gandhi NR, Moll AP, Lalloo U, Pawinski R, Zeller K, Moodley P et al.; Tugela Ferry Care and Research (TFCaRes) Collaboration. Successful integration of tuberculosis and HIV treatment in rural South Africa: the Sizonq'oba study. J Acquir Immune Defic Syndr 2009;50:3743. doi: http://dx.doi.org/10.1097/QAI.0b013e31818ce6c4 PMID: 19295333
40. Garrido C, Zahonero N, Fernándes D, Serrano D, Silva AR, Ferraria N et al. Subtype variability, virological response and drug resistance assessed on dried blood spots collected from HIV patients on antiretroviral therapy in Angola. J Antimicrob Chemother 2008;61:6948. doi: http://dx.doi.org/10.1093/jac/dkm515 PMID: 18218644
41. Hegazi A, Bailey RL, Ahadzie B, Alabi A, Peterson K. Literacy, education and adherence to antiretroviral therapy in The Gambia. AIDS Care 2010;22:13405. doi: http://dx.doi.org/10.1080/09540121003693514 PMID: 20711888
42. Kamya MR, Mayanja-Kizza H, Kambugu A, Bakeera-Kitaka S, Semitala F, Mwebaze-Songa P et al.; Academic Alliance for AIDS Care and Prevention in Africa. Predictors of long-term viral failure among Ugandan children and adults treated with antiretroviral therapy. J Acquir Immune Defic Syndr 2007;46:18793. doi: http://dx.doi.org/10.1097/QAI.0b013e31814278c0 PMID: 17693883
43. Kouanfack C, Montavon C, Laurent C, Aghokeng A, Kenfack A, Bourgeois A et al. Low levels of antiretroviral-resistant HIV infection in a routine clinic in Cameroon that uses the World Health Organization (WHO) public health approach to monitor antiretroviral treatment and adequacy with the WHO recommendation for second-line treatment. Clin Infect Dis 2009;48:131822. doi: http://dx.doi.org/10.1086/597779 PMID: 19320592
44. Landman R, Poupard M, Diallo M, Ngom Gueye NF, Diakhate N, Ndiaye B et al. Tenofovir-emtricitabine-efavirenz in HIV-I-infected adults in Senegal: a 96-week pilot trial in treatment-naive patients. J Int Assoc Physicians AIDS Care (Chic) 2009;8:37984. doi: http://dx.doi.org/10.1177/1545109709344352 PMID: 19755618
45. Laurent C, Ngom Gueye NF, Ndour CT, Gueye PM, Diouf M, Diakhaté N et al.; ANRS 1215/1290 Study Group. Long-term benefits of highly active antiretroviral therapy in Senegalese HIV-1-infected adults. J Acquir Immune Defic Syndr 2005;38:147. doi: http://dx.doi.org/10.1097/00126334-200501010-00003 PMID: 15608518
46. Lester RT, Ritvo P, Mills EJ, Kariri A, Karanja S, Chung MH et al. Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial. Lancet 2010;376:183845. doi: http://dx.doi.org/10.1016/S0140-6736(10)61997-6 PMID: 21071074
47. Lyagoba F, Dunn DT, Pillay D, Kityo C, Robertson V, Tugume S et al.; DART Virology and Trial Team. Evolution of drug resistance during 48 weeks of zidovudine/lamivudine/tenofovir in the absence of real-time viral load monitoring. J Acquir Immune Defic Syndr 2010;55:27783. doi: http://dx.doi.org/10.1097/QAI.0b013e3181ea0df8 PMID: 20686411
48. Moore E, Beadsworth MBJ, Chaponda M, Mhango B, Faragher B, Njala J et al. Favourable one-year ART outcomes in adult Malawians with hepatitis B and C co-infection. J Infect 2010;61:15563. doi: http://dx.doi.org/10.1016/j.jinf.2010.04.009 PMID: 20470823
49. Mujugira A, Wester CW, Kim S, Bussmann H, Gaolathe T et al. Patients with advanced HIV type 1 infection initiating antiretroviral therapy in Botswana: treatment response and mortality. AIDS Res Hum Retroviruses 2009;25:12733. doi: http://dx.doi.org/10.1089/aid.2008.0172 PMID: 19239353
50. Mutevedzi PC, Lessells RJ, Heller T, Bärnighausen T, Cooke GS, Newell M-L. Scale-up of a decentralized HIV treatment programme in rural KwaZulu-Natal, South Africa: does rapid expansion affect patient outcomes? Bull World Health Organ 2010;88:593600. doi: http://dx.doi.org/10.2471/BLT.09.069419 PMID: 20680124
51. Nachega JB, Chaisson RE, Goliath R, Efron A, Chaudhary MA, Ram M et al. Randomized controlled trial of trained patient-nominated treatment supporters providing partial directly observed antiretroviral therapy. AIDS 2010;24:127380. PMID: 20453627
52. Nachega JB, Hislop M, Nguyen H, Dowdy DW, Chaisson RE, Regensberg L et al. Antiretroviral therapy adherence, virologic and immunologic outcomes in adolescents compared with adults in southern Africa. J Acquir Immune Defic Syndr 2009;51:6571. doi: http://dx.doi.org/10.1097/QAI.0b013e318199072e PMID: 19282780
53. Ndembi N, Goodall RL, Dunn DT, McCormick A, Burke A, Lyagoba F et al.; Development of Antiretroviral Treatment in Africa Virology Group and Trial Team. Viral rebound and emergence of drug resistance in the absence of viral load testing: a randomized comparison between zidovudine-lamivudine plus nevirapine and zidovudine-lamivudine plus abacavir. J Infect Dis 2010;201:10613. doi: http://dx.doi.org/10.1086/648590 PMID: 19938977
54. Oyomopito R, Lee MP, Phanuphak P, Lim PL, Ditangco R, Zhou J et al.; TREAT Asia HIV Observational Database. Measures of site resourcing predict virologic suppression, immunologic response and HIV disease progression following highly active antiretroviral therapy (HAART) in the TREAT Asia HIV Observational Database (TAHOD). HIV Med 2010;11:51929. PMID: 20345881
55. Ramadhani HO, Thielman NM, Landman KZ, Ndosi EM, Gao F, Kirchherr JL et al. Predictors of incomplete adherence, virologic failure, and antiviral drug resistance among HIV-infected adults receiving antiretroviral therapy in Tanzania. Clin Infect Dis 2007;45:14928. doi: http://dx.doi.org/10.1086/522991 PMID: 17990233
56. Sarna A, Luchters S, Geibel S, Chersich MF, Munyao P, Kaai S et al. Short- and long-term efficacy of modified directly observed antiretroviral treatment in Mombasa, Kenya: a randomized trial. J Acquir Immune Defic Syndr 2008;48:6119. doi: http://dx.doi.org/10.1097/QAI.0b013e3181806bf1 PMID: 18645509
57. Seyler C, Anglaret X, Dakoury-Dogbo N, Messou E, Touré S, Danel C et al.; ANRS 1203 Study Group. Medium-term survival, morbidity and immunovirological evolution in HIV-infected adults receiving antiretroviral therapy, Abidjan, Côte d'Ivoire. Antivir Ther 2003;8:38593. PMID: 14640385
58. Vanni T, Morejón KM, Santana RC, Melo Ld, Ferrão SB, Amorim AP et al. Comparison of the effectiveness of initial combined antiretroviral therapy with nelfinavir or efavirenz at a university-based outpatient service in Brazil. Braz J Med Biol Res 2007;40:9639. doi: http://dx.doi.org/10.1590/S0100-879X2007000700011 PMID: 17653450
59. Bertagnolio S, Kelley K, Saadani Hassani A, Obeng-Aduasare Y, Jordan M. Surveillance of transmitted and acquired HIV drug resistance using WHO surveys in resource-limited settings. In: Proceedings of the 18th Conference on Retroviruses and Opportunistic Infections, 27 February to 2 March 2011, Boston, United States of America. Alexandria: CROI; 2011. Available from: http://www.retroconference.org/2011/Abstracts/41940.htm [accessed 24 January 2013] .
60. Calmy A, Balestre E, Boulle A, Thiébaut R, Bonnet F, Sprinz E et al. Prediction of CD4 cell count slope in patients with virological failure to first-line of antiretroviral combinations in resource-limited settings. Geneva: International AIDS Society 2010 (abstract CDB081 2009 11/23/2010). Available from: http://www.iasociety.org/Default.aspx?pageId=11&abstractId=200722018 [accessed 24 January 2013] .
61. Chang L, Kagaayi J, Nakigozi G, Ssempijja V, Serwadda D, Packer A et al. Effect of peer health workers and a mobile phone support intervention on AIDS care in Rakai, Uganda: a cluster-randomized trial. Geneva: International AIDS Society; 2010 (abstract WEPED158 2009 11/23/2010). Available from: http://www.iasociety.org/Default.aspx?pageId=11&abstractId=200722818 [accessed 24 January 2013] .
62. Chasombat S, Kantipong P, Pathipvanich P, Luakamlung N, Malai S, Kohreanudom S et al. Thailand national surveillance system to determine the development of HIV drug resistance among ARV treated patients. Geneva: International AIDS Society; 2010. (abstract THPE0427 2010 11/23/2010). Available from: http://www.iasociety.org/Default.aspx?pageId=11&abstractId=200739558 [accessed 24 January 2013] .
63. Crabtree-Ramírez B, Caro-Vega Y, Sierra-Madero J. Late diagnosis of HIV infection results in a higher mortality but not in virological failure after starting HAART. Geneva: International AIDS Society; 2010 (abstract THPE0122 2010 11/23/2010). Available from: http://www.iasociety.org/Default.aspx?pageId=11&abstractId=200740133 [accessed 24 January 2013] .
64. Lockman S, Smeaton L, Ogwu A, Shapiro R, Leidner J, Powis K et al. Long-term maternal and pediatric virologic outcomes on nevirapine-based HAART following receipt of peripartum single-dose nevirapine or placebo, Botswana. In: Proceedings of the 16th Conference on Retroviruses and Opportunistic Infections, 811 February 2009, Montréal, Canada. Alexandria: CROI; 2009. Available from: http://www.retroconference.org/2009/Abstracts/36058.htm [accessed 24 January 2013] .
65. Messou E, Chaix M-L, Gabillard D, Minga A, Losina E, N'Dri-Yoman T et al. Strong association between medication possession ratio and early virological outcomes in adults on ART in Côte d'Ivoire. In: Proceedings of the 17th Conference on Retroviruses and Opportunistic Infections, 1619 February 2010, San Francisco, United States of America. Alexandria: CROI; 2010. Available from: http://www.retroconference.org/2010/Abstracts/38493.htm [accessed 24 January 2013] .
66. Ratsela A, Polis M. Phidisa II: A randomized 2x2 factorial trial comparing initial therapy of efavirenz with lopinavir/ritonavir and zidovudine + didanosine with stavudine + lamivudine in treatment-naïve HIV-infected persons with < 200 CD4+ cells/mm3 or a prior AIDS diagnosis. In: Proceedings of the 16th Conference on Retroviruses and Opportunistic Infections, 811 February 2009, Montréal, Canada. Alexandria: CROI; 2009. Available from: http://www.retroconference.org/2009/Abstracts/34300.htm [accessed 24 January 2013] .
67. Reynolds S, Sendagire H, Newell K, Castelnuovo B, Kiragga A, Namugga I et al. Routine VLM reduces the rate of accumulated genotypic resistance to commonly used ART in Uganda. In: Proceedings of the 18th Conference on Retroviruses and Opportunistic Infections, 27 February to 2 March 2011, Boston, United States of America. Alexandria: CROI; 2011. Available from: http://www.retroconference.org/2011/Abstracts/41522.htm [accessed 24 January 2013] .
68. Scarsi K, Darin K, Rawizza H, Meloni S, Chang C, Olaitan R et al. TDF-3TC-NVP is inferior to AZT-3TC-NVP in a large ART program in Nigeria. Geneva: International AIDS Society; 2010 (abstract THPE0115 2010 11/23/2010). Available from: http://www.iasociety.org/Default.aspx?pageId=11&abstractId=200738740 [accessed 24 January 2013] .
69. Stafford K, Hossain M, Mesubi R, Etienne M, Oshi R, Bositis A et al. Viral suppression outcomes of patients using nevirapine in combination with tenofovir and a cytosine analog (3TC or FTC) as a first line regimen in resource limited settings. Geneva: International AIDS Society; 2010 (abstract CDB080 2009 11/23/2010). Available from: http://www.iasociety.org/Default.aspx?pageId=11&abstractId=200721588 [accessed 24 January 2013] .
70. van Leeuwen R, Katlama C, Murphy RL, Squires K, Gatell J, Horban A et al. A randomized trial to study first-line combination therapy with or without a protease inhibitor in HIV-1-infected patients. AIDS 2003;17:98799. doi: http://dx.doi.org/10.1097/00002030-200305020-00007 PMID: 12700448
71. Staszewski S, Morales-Ramirez J, Tashima KT, Rachlis A, Skiest D, Stanford J et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med 1999;341:186573. doi: http://dx.doi.org/10.1056/NEJM199912163412501 PMID: 10601505
72. Bartlett JA, Fath MJ, Demasi R, Hermes A, Quinn J, Mondou E et al. An updated systematic overview of triple combination therapy in antiretroviral-naive HIV-infected adults. AIDS 2006;20:205164. doi: http://dx.doi.org/10.1097/01.aids.0000247578.08449.ff PMID: 17053351
73. Bansi L, Sabin C, Gilson R, Gazzard B, Leen C, Anderson J et al.; UK Collaborative HIV Cohort Study. Virological response to initial antiretroviral regimens containing abacavir or tenofovir. J Infect Dis 2009;200:7104. doi: http://dx.doi.org/10.1086/605024 PMID: 19635022
74. Uy J, Armon C, Buchacz K, Wood K, Brooks JT; HOPS Investigators. Initiation of HAART at higher CD4 cell counts is associated with a lower frequency of antiretroviral drug resistance mutations at virologic failure. J Acquir Immune Defic Syndr 2009;51:4503. doi: http://dx.doi.org/10.1097/QAI.0b013e3181acb630 PMID: 19474757
75. Moore DM, Mermin J, Awor A, Yip B, Hogg RS, Montaner JS. Performance of immunologic responses in predicting viral load suppression: implications for monitoring patients in resource-limited settings. J Acquir Immune Defic Syndr 2006;43:4369. doi: http://dx.doi.org/10.1097/01.qai.0000243105.80393.42 PMID: 17019367
76. Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach 2006 revision. Geneva: World Health Organization; 2006.
77. Hoffmann CJ, Charalambous S, Sim J, Ledwaba J, Schwikkard G, Chaisson RE et al. Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. Clin Infect Dis 2009;49:192835. doi: http://dx.doi.org/10.1086/648444 PMID: 19911963
78. Wilson D, Keiluhu AK, Kogrum S, Reid T, Seriratana N, Ford N et al. HIV-1 viral load monitoring: an opportunity to reinforce treatment adherence in a resource-limited setting in Thailand. Trans R Soc Trop Med Hyg 2009;103:6016. doi: http://dx.doi.org/10.1016/j.trstmh.2008.11.007 PMID: 19110288
79. Glaser R. Instructional technology and the measurement of learning outcomes: some questions. In: Notterman JM, editor. The evolution of psychology: fifty years of the American Psychologist. Washington: American Psychological Association; 1963. pp. 33742.
80. HIV drug resistance early warning indicators: World Health Organization indicators to monitor HIV drug resistance prevention at antiretroviral treatment sites. June 2010 update. Geneva: World Health Organization; 2010. Available from: www.unaids.org.br/biblioteca/links/OPAS.../OPAS%2014.pdf [accessed 21 February 2013] .
(Submitted: 16 September 2012 Revised version received: 1 January 2013 Accepted: 21 January 2013 Published online: 21 February 2013)