These new recombinant forms may reflect the diversification of the HIV-1 epidemic in this country, as a result of both migration from neighbouring countries and recombination events within the local population. This increasing diversity could lead to the emergence of new resistance pathways that could affect first-line

therapy in the future. Several studies have suggested that non-B isolates show a different pattern of resistance mutations from subtype B [10,11]. Reports have shown that the mutation V106M confers resistance to NNRTIs in subtype C HIV [12], and is preferentially selected in vivo [13], and that the D30N mutation is not preferentially selected in HIV-1 click here subtype C in the development of resistance to nelfinavir [14]. We have previously shown that subtype K reverse transcriptase may preferentially select for the thymidine analogue mutation 2 (TAM-2) pathways in the presence of NRTIs [15]. Differences in the way in which resistance evolves among subtypes may mean that some second-line regimens will be less effective than previously thought. Moreover, treatment of patients with primary resistance will be compromised from the DNA/RNA Synthesis inhibitor outset, potentially leading to onward transmission of drug-resistant HIV. Use of compromised treatment regimens may not result in the expected prevention benefits; that is, decreased HIV transmission. The

World Health Organization (WHO) currently recommends first-line therapy with two NRTIs and one NNRTI, a combination with high efficacy, tolerability and simplicity and low cost, and showing high adherence to treatment [16]. First-line regimens in Mali are based on this recommendation. Antiretroviral drugs have been made available in Mali

since 1997, and have been free since 2004. The recommended first-line regimen is a fixed-dose combination of stavudine/lamivudine/nevirapine, currently prescribed free of charge for the majority of patients. The alternative first-line regimens are zidovudine/lamivudine/efavirenz and zidovudine/lamivudine/nevirapine. The recommended second-line regimen is abacavir/didanosine/indinavir, and the alternative drugs are tenofovir Histone demethylase and lopinavir [7] or indinavir/ritonavir. An increase in the prevalence of primary resistance could jeopardize these second-line options. The availability of antiretrovirals has brought great hope to HIV-infected individuals in resource-limited countries. The emergence and transmission of resistant virus could compromise the effectiveness of specific treatments in areas where therapeutic options are limited [17]. There were limited data on primary antiretroviral drug resistance before 2000 in these countries [18]. Preliminary data suggest that resistance may be emerging in countries currently scaling up access to antiretroviral therapy [19]. Data from Africa support this suggestion.