Introduction: There is a dearth of information on the prevalence of antiretroviral resistance in Africa. Previously, financial constraints limited the use of maximally suppressive regimens. Substantial reductions in drug costs have recently been implemented that substantially improve access to potent antiretroviral therapies. The majority of people treated prior to 2001, however, received sequential therapy with dual nucleosides. This, together with the widespread use of short-course single- or dual-drug regimens to prevent perinatal HIV-1 transmission, could promote the emergence of drug resistance.

Methods: We report  genotypic test results on 120 patients from South Africa (87), Botswana (31), and Zimbabwe (2) who were failing antiretroviral therapy. Virological failure was defined as a rebound in viral load of >0.6 log from nadir, or a persistent increase in viral load to > 1000 copies/mL. 30 were failing their first HAART regimen and 90 were no longer responding to subsequent therapies. Samples were tested using either the Visible Genetics TrueGene Assay (109 samples), or the ABI ViroSeq test (11 samples).

Results: Recognised resistance mutations were not detected in 15 samples (11%); lack of adherence and/or pharmacological factors were assumed to be responsible for virological failure. Resistance to 1 class of antiretroviral agents (ARV) was detected in 11 samples (8%), and to 2 or more classes in 104 samples (77%). The M184V, K103N, and thymidine analogue resistance mutations were most frequently encountered. Numerous polymorphisms were evident in the protease gene, perhaps reflecting the preponderance of non-clade B virus in the southern African region. 6 samples (4%) contained the multi-nucleoside resistance mutations Q151M (4 samples) and T69S-S (2 samples). These viral sequences from these samples contained primary mutations associated with resistance to NNRTIs and PIs. This is the first report of multi-drug resistant HIV-1 from southern Africa. The 6 patients were heavily pre-treated with sequential dual nucleoside regimens and were failing their first or second HAART combination. 

Conclusions: Despite previously low rates of antiretroviral use, there is a significant prevalence of drug-resistant HIV-1 in southern Africa. The intense cycle of transmission together with a background of drug-resistant virus poses a considerable risk for widespread dissemination of these strains. Surveillance of primary drug-resistance as well as resistance patterns among patients failing therapy is now warranted in the southern African region.