Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review

Summary

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.

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.