According to World Health Organization (WHO) estimates, 33.4 million people were infected with the human immunodeficiency virus (HIV) type 1 globally at the end of 2008.1 Sub-Saharan Africa and Asia are the two regions that have the highest HIV prevalence, with 22.4 and 4.7 million people infected, respectively.1 During the 5 years prior, access to combination antiretroviral therapy (ART) in low- and middle-income countries increased 10-fold to reach 4 million people, providing coverage to 28% of those in need.2 Several studies have reported significant reductions in HIV-related morbidity and mortality for individuals with access to treatment in these regions.3–5 In resource-limited settings, to facilitate the rapid expansion of access to ART, WHO recommends a standardized, public-health approach.6 This is in contrast to the individualized patient-management strategies in developed countries, based on routinely available diagnostic monitoring.7 Standardized first-line ART regimens consist of a non-nucleoside reverse transcriptase inhibitor (NNRTI) and a dual nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbone, available in some countries as generic fixed-dose combinations.6 Recommended second-line regimens combine a ritonavir-boosted protease inhibitor (PI) with two previously unused and/or recycled NRTIs.6
Routine HIV viral-load monitoring is not generally available in resource-limited countries and treatment failure is frequently identified based on immunological definitions and/or the occurrence of clinical events.6 Virological breakthrough may be detected late while the failing regimen is continued, thus facilitating the acquisition and accumulation of drug resistance-associated mutations.8 Drug-resistant HIV variants may compromise the effectiveness of subsequent lines of treatment and their transmission to newly infected individuals has severe public health consequences.9,10 To date, ART programmes have been implemented without accompanying HIV drug resistance (HIVDR) monitoring. Monitoring studies are hampered by the lack of a molecular laboratory infrastructure required for genotypic resistance testing, logistical challenges related to maintaining specimen integrity in remote settings and the high costs of testing.11 Challenges to scaling up ART in resource-limited countries, such as absence of routine virological monitoring and limited choices of drug regimen, advocate for the development of a global public-health framework to monitor and prevent the emergence of HIVDR and thus maximize long-term ART effectiveness.12
HIV-1 subtype B is the predominant viral subtype in North America, Western Europe and Australia, and antiretroviral (ARV) drugs have been developed on this subtype. However, in sub-Saharan Africa and Asia, the genetic diversity in HIV subtypes and circulating recombinant forms (CRFs), resulting from recombination between subtypes within a dually infected person, is extensive.13 Although current evidence is limited, some reports have suggested that the propensity to develop HIVDR and the spectrum of mutations that emerge during drug selective pressure, may differ across subtypes and CRFs.14–17 Viral heterogeneity may, therefore, have implications for rates of disease progression and patient response to ART, warranting further study of inter-subtype differences in mutational pathways to resistance.
To help assess the extent of HIVDR in sub-Saharan Africa and Asia, a collaborative bi-regional programme was established, called LAASER [Linking African and Asian Societies for an Enhanced Response (LAASER) to HIV/AIDS; http://www.laaser-hivaids.org] with the primary aim of increasing regional capacities for the monitoring of HIVDR. PharmAccess Foundation, a non-profit organization dedicated to the strengthening of health systems and improving access to quality basic health care in sub-Saharan Africa, has developed the PharmAccess African Studies to Evaluate Resistance (PASER). TREAT Asia (Therapeutics, Research, Education and AIDS Training in Asia) is a network of clinics, hospitals and research institutions working to ensure safe and effective delivery of HIV/AIDS treatment throughout the Asia-Pacific and has developed the TREAT Asia Studies to Evaluate Resistance (TASER). Both PASER and TASER programmes incorporate a monitoring and evaluation (M) and a surveillance (S) protocol. Laboratories providing genotyping results for PASER and TASER are required to participate in the TREAT Asia Quality Assurance Scheme (TAQAS), which is an ongoing assessment programme to build genotyping laboratory capacity, described elsewhere.18 The focus of this cohort profile is the monitoring and evaluation protocols, PASER-M and TASER-M.