Concern that a rapid
massive scale-up of antiretroviral therapy (ART) would lead to the widespread emergence and transmission of drug-resistant virus1,2
was expressed early in the development of ART access programs in Africa. These were based largely on the challenges associated with early treatments (high pill burden, frequent dosing, toxicity) and financial constraints that would cause drug “stock-outs” and prohibit essential laboratory monitoring.3
Although some programs in sub-Saharan Africa have experienced difficulty maintaining a constant supply of drugs,4
pooled data obtained before the widespread roll-out of ART programs indicate that adherence levels in Africa have been as high, or higher, than as those in North America (77% vs. 55%, respectively, p
Although high levels of adherence may be maintained following widespread roll-out of ART, missed drug pick-ups due to family obligations and travel costs have been leading causes of viremia and the selection of drug resistance in Africa.6–8
Transmitted drug resistance (TDR) levels vary widely, depending on factors such as the population studied, availability, and access to ART, duration of the treatment programs, quality of medical care, risk-taking behaviors, mode of transmission, and viral subtype.9,10
In developed countries, the use of mono therapy and dual therapy in the pre-highly active antiretroviral therapy (HAART) era (1980s and early 1990s) resulted in the rapid emergence of TDR with peak levels as high as 27%11–17
in some population groups. However, recent evidence suggests that TDR is decreasing with the current levels ranging between 5% and 15% in Europe (2007) and 10% and 18% in the United States.18
Since transmitted resistance can seriously limit future therapeutic options, North American and European treatment guidelines recommend resistance testing for all treatment-naive patients prior to the initiation of HAART. This provides an opportunity to avoid ineffective drug combinations and allows for individualized optimization of first-line HAART.
In most African countries, formalized ART became available in the public health system only after 2002/2003 with the introduction of first-line treatment with combination drug regimens consisting of two nucleoside combined with one nonnucleoside reverse transcriptase inhibitor (NRTIs, NNRTIs). These simple and affordable treatments have been effective and, until recently, levels of primary resistance have remained low (i.e., <5%). However, several recent studies in southern (Lusaka, Durban, Cape Town) and East (Entebbe, Kigali, Kilifi) Africa have reported TDR rates ≥5%.19, 20
All of these studies were conducted in large urban centers, either in young primagravidas attending antenatal clinics (ANC) or in treatment-naive individuals starting ART.
In resource-constrained countries where a substantial proportion of the population may be in need of treatment (i.e., have an AIDS-defining illness and/or a CD4+
T cell count <350 cells/μl), WHO recommends resistance genotyping of remnant specimens collected from recently infected treatment-naive individuals, either young (<25 years of age) primagravida women, individuals consecutively diagnosed with HIV-1 in seroprevalence surveys, or individuals who have laboratory confirmed evidence of recent infection using a test such as the cBED assay.21
With approximately 57 samples, a binomial sequential sampling method is recommended to estimate the potential prevalence of resistance as <5%, 5–15%, or >15%.22,23
To date, most WHO “threshold” surveys have been conducted in the antenatal setting. Whether the results can be extrapolated to the general population remains to be determined. Population-based estimates of TDR are rare but can be derived from surveillance, prevention, and vaccine studies including the identification of individuals with laboratory evidence of recent infection.
The current population-based study is nested within a large 7-year HIV-1 surveillance study conducted in the Hlabisa subdistrict of rural KwaZulu-Natal (KZN).24,25
Using samples collected in 2010, we estimated the level of transmitted drug resistance in a group of 72 recent seroconverters (defined by a confirmed positive serological test in 2010 preceded by a negative test in the previous surveillance round in which the person participated). To track temporal changes and assess demographic differences in TDR, we compared our population-based results to previous resistance studies conducted in diverse setting across South Africa.