Rational use of antiretroviral therapy in low-income and middle-income countries: optimizing regimen sequencing and switching

During the 4 years to the end of 2007, the number of people in low-income and middle-income countries (LMICs) receiving antiretroviral therapy (ART) increased from 400 000 to 3 million [1,2]. Although early mortality [3] and retention in care [4] remain significant challenges, the majority of reports from LMICs have shown encouraging immunological, virological and survival outcomes [5 12]. Reported rates of switching to second-line ART regimens have been lower than expected [13 15], in part due to actual rates of treatment success, but mainly because of limited access to both virological monitoring [16] and second-line drugs [14]. Clinicians have also been reluctant to switch therapy [15] due to regimen cost, complexity, inconvenience and lack of subsequent treatment options. As cohorts mature and expand and access to virological monitoring and second-line regimens increase, however, rates of diagnosed treatment failure and switch to second-line regimens will increase [17]. As the cost of second-line regimens are currently three to 20 times more expensive than that of first-line regimens [18], these increases will challenge the cost-effectiveness [19,20] and sustainability [21] of HIV-treatment programmes.An effective response to the challenges of HIV treatment failure in LMICs must include reductions in the cost of second-line agents [22], but changes to commercial regulations, particularly in India, suggest the scale of price reductions seen with first-line agents are unlikely to occur with second-line agents. Strategies to maximize the effectiveness of first-line and second-line regimens and optimize the timing of regimen switching are required to fully utilize the survival benefit of available treatment options, maintain programme cost-effectiveness and enable achievement of universal access to HIV treatment. A comprehensive strategy must be evidence based and focused on the rational long-term use of ART at a population level. The objective of this review is to support the development of these strategies by providing an overview of available evidence with an emphasis on regimen sequencing and switching.