ReviewVirological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review
Introduction
An estimated 33 million people worldwide are infected with HIV, most of whom live in sub-Saharan Africa. Highly active antiretroviral therapy (HAART) was introduced in 1996 in developed countries and acknowledged as the standard of care for people with HIV/AIDS ever since. When the Doha declaration was adopted in 2001, which enabled developing countries to circumvent patent rights to increase access to essential medicines, HAART became more widely accessible in resource-limited settings. Subsequently, large funds were provided by the US President's Emergency Plan for AIDS Relief (PEPFAR), which was established in 2002, and by the Global Fund for AIDS, Tuberculosis and Malaria, operating since 2003. In that same year WHO launched their 3 by 5 Initiative, aimed at providing 3 million people with antiretroviral therapy by the end of 2005. Although this goal was not met, the initiative led to a substantial increase in the roll-out of antiretroviral therapy and 2 years later, by the end of 2007, nearly 3 million people worldwide were receiving HAART. The greatest increase in the number of people receiving treatment was in sub-Saharan Africa.1
Early results from antiretroviral treatment programmes in African countries have been promising, showing similar results to those in developed countries.2, 3 However, long-term data are scarce; the weighted average follow-up in 32 papers included in a review4 on retention of patients programmes in sub-Saharan Africa was less than 10 months.
Because of insufficient financial and logistical means, laboratory monitoring of patients receiving antiretroviral therapy is limited in sub-Saharan African countries. The cost of laboratory monitoring of patients has meant that HIV-RNA measurements and genotypic resistance tests are not generally recommended by WHO and are therefore not done consistently. As a substitute, recommendations have been made by WHO to define the failure of antiretroviral therapy by use of clinical criteria and CD4 T-cell counts. Several studies in African settings, however, have shown that the association between these determinants and virological failure is limited.5, 6, 7
Treatment switches in patients who do not experience virological failure will increase treatment costs and might limit treatment options in the future. Unnecessary loss of treatment options is especially hazardous since only one second-line antiretroviral therapy regimen is available in most sub-Saharan African countries.
Alternatively, continuation of a treatment regimen when patients experience virological failure might compromise patients' immunological and clinical status and, because of ongoing viral replication, lead to the selection of viruses with enhanced resistance to antiretroviral drugs. Resistance outcomes across programmes of antiretroviral treatment with differing intensities of virological monitoring were compared, showing how useful regular virological monitoring is in both resource-rich and resource-limited settings.8
In our Review, we assess the results of programmes of antiretroviral treatment in sub-Saharan Africa that reported any relevant virological outcome of first-line HAART in adults infected with HIV. We systematically analyse virological suppression (virological success) and failure as well as selection for drug resistance and discuss the possible implications of these findings on future treatment strategies in this region.
Section snippets
Search strategy
We systematically reviewed published work in accordance with QUORUM guidelines.9 We searched the online databases PubMed and Embase for articles available in English before June 1, 2009, with the terms “Africa” or “Afrika” or “sub-Sahara Africa” or “sub Sahara Africa” or “southern Africa” AND “HIV” or “AIDS” or “human immunodeficiency virus” or “acquired immunodeficiency syndrome” AND “antiretroviral therapy” or “antiretroviral*” or “HAART” or “ART” or “ARV” AND “viral load” or “HIV-RNA” or
Results
The search strategy identified 902 potential articles and 587 potential abstracts (figure). 1199 reports were excluded after checking the titles, mainly because they dealt with obviously different issues, and the abstracts of the remaining 290 reports were reviewed consequently excluding a further 149. Of the remaining 141 reports, the full-length text (if it concerned papers rather than abstracts) were retrieved and reviewed independently in duplicate. In this process another 52 reports were
Discussion
We identified 69 peer-reviewed papers and 20 abstracts that provided information on virological outcome of antiretroviral treatment programmes in sub-Saharan Africa.
Short-term results are promising. The proportions of patients with on-treatment success after 6–24 months of first-line therapy are comparable to those from developed countries, but intention-to-treat data are less optimistic.
In guidance published by WHO, a list of targets for antiretroviral therapy programmes in resource-limited
Conclusion
Achieving similar response rates in sub-Saharan Africa with those seen in developed countries is a substantial accomplishment considering the rate at which programme expansions have taken place since 2003 and the substantial limitations in patient monitoring. However, results from intention-to-treat analyses showed decreased response compared with on-treatment analyses, probably caused by a more advanced stage of infection at start of treatment in African patients. Therefore, efforts should be
References (107)
- et al.
Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment
Lancet
(2006) - 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) - et al.
Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement—Quality of Reporting of Meta-analyses
Lancet
(1999) - et al.
Effectiveness and safety of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine in HIV-1-infected adults in Cameroon: open-label multicentre trial
Lancet
(2004) - et al.
Viraemia and HIV-1 drug resistance mutations among patients receiving antiretroviral treatment in Mozambique
Trans R Soc Trop Med Hyg
(2009) - et al.
Adherence to antiretroviral therapy in a home-based AIDS care programme in rural Uganda
Lancet
(2006) Towards universal access: scaling up priority HIV/AIDS interventions in the health sector
(2008)- et al.
Effectiveness of highly active antiretroviral therapy administered by general practitioners in rural South Africa
Eur J Clin Microbiol Infect Dis
(2008) - et al.
Patient retention in antiretroviral therapy programs in sub-Saharan Africa: a systematic review
PLoS Med
(2007) - et al.
Utility of CD4 cell counts for early prediction of virological failure during antiretroviral therapy in a resource-limited setting
BMC Infect Dis
(2008)
Evaluation of the WHO criteria for antiretroviral treatment failure among adults in South Africa
AIDS
Anthropometric and immunological success of antiretroviral therapy and prediction of virological success in west African adults
Bull World Health Organ
Update of the drug resistance mutations in HIV-1: spring 2008
Top HIV Med
Subtype variability, virological response and drug resistance assessed on dried blood spots collected from HIV patients on antiretroviral therapy in Angola
J Antimicrob Chemother
Out-of-pocket costs of HAART limit HIV treatment responses in Botswana's private sector
AIDS
Five-year outcomes of initial patients treated in Botswana's National Antiretroviral Treatment Program
AIDS
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
Mutations and polymorphisms associated with antiretroviral drugs in HIV-1C-infected African patients
Antivir Chem Chemother
The reverse transcriptase 67N 70R 215Y genotype is the predominant TAM pathway associated with virologic failure among HIV type 1C-infected adults treated with ZDV/ddI-containing HAART in southern Africa
AIDS Res Hum Retroviruses
Initial response to highly active antiretroviral therapy in HIV-1C-infected adults in a public sector treatment program in Botswana
J Acquir Immune Defic Syndr
Characterization of drug-resistance mutations in HIV-1 isolates from non-HAART and HAART treated patients in Burkina Faso
J Med Virol
HIV drug resistance pattern among HAART-exposed patients with suboptimal virological response in Ouagadougou, Burkina Faso
J Acquir Immune Defic Syndr
Low prevalence of detectable HIV plasma viremia in patients treated with antiretroviral therapy in Burkina Faso and Mali
J Acquir Immune Defic Syndr
Characterization of drug resistance in antiretroviral-treated patients infected with HIV-1 CRF02_AG and AGK subtypes in Mali and Burkina Faso
Antivir Ther
Field assessment of generic antiretroviral drugs: a prospective cohort study in Cameroon
Antivir Ther
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
Long-term safety, effectiveness and quality of a generic fixed-dose combination of nevirapine, stavudine and lamivudine
AIDS
Antiretroviral drug resistance and routine therapy, Cameroon
Emerg Infect Dis
Virologic and immunologic outcomes and programmatic challenges of an antiretroviral treatment pilot project in Abidjan, Côte d'Ivoire
AIDS
Medium-term survival, morbidity and immunovirological evolution in HIV-infected adults receiving antiretroviral therapy, Abidjan, Côte d'Ivoire
Antivir Ther
Impact of genotypic drug resistance mutations on clinical and immunological outcomes in HIV-infected adults on HAART in west Africa
AIDS
Implementation of an antiretroviral access program for HIV-1-infected individuals in resource-limited settings: clinical results from 4 African countries
J Acquir Immune Defic Syndr
Short- and long-term efficacy of modified directly observed antiretroviral treatment in Mombasa, Kenya: a randomized trial
J Acquir Immune Defic Syndr
Evaluation of antiretroviral therapy results in a resource-poor setting in Blantyre, Malawi
Trop Med Int Health
Excessive early mortality in the first year of treatment in HIV type 1-infected patients initiating antiretroviral therapy in resource-limited settings
AIDS Res Hum Retroviruses
HIV drug resistance after the use of generic fixed-dose combination stavudine/lamivudine/nevirapine as standard first-line regimen
AIDS
Evaluating adherence to highly active antiretroviral therapy with use of pill counts and viral load measurement in the drug resources enhancement against AIDS and malnutrition program in Mozambique
Clin Infect Dis
Management of HIV-1 infection with a combination of nevirapine, stavudine, and lamivudine: a preliminary report on the Nigerian antiretroviral program
J Acquir Immune Defic Syndr
Direct observation therapy-highly active antiretroviral therapy in a resource-limited setting: the use of community treatment support can be effective
Int J STD AIDS
Antiviral efficacy and resistance in patients on antiretroviral therapy in Kigali, Rwanda: the real-life situation in 2002
HIV Med
Poor efficacy and tolerability of stavudine, didanosine, and efavirenz-based regimen in treatment-naive patients in Senegal
MedGenMed
Mortality and causes of death in adults receiving highly active antiretroviral therapy in Senegal: a 7-year cohort study
AIDS
Cited by (245)
Seemingly Unrelated Regression Analysis of the Cost and Health-Related Quality of Life Outcomes of the REVAMP Randomized Clinical Trial
2023, Value in Health Regional IssuesSystematic review of interventions aimed at improving HIV adherence to care in low- and middle-income countries in Sub-Saharan Africa
2022, Journal of Infection and Public HealthAcquired HIV drug resistance mutations on first-line antiretroviral therapy in Southern Africa: Systematic review and Bayesian evidence synthesis
2022, Journal of Clinical EpidemiologyThe health impact of free access to antiretroviral therapy in South Africa
2022, Social Science and MedicineDeterminants of health-related quality of life in people with Human Immunodeficiency Virus, failing first-line treatment in Africa
2023, Health and Quality of Life OutcomesMachine learning to predict virological failure among HIV patients on antiretroviral therapy in the University of Gondar Comprehensive and Specialized Hospital, in Amhara Region, Ethiopia, 2022
2023, BMC Medical Informatics and Decision Making