WHO approach to track HIV drug resistance emergence and transmission in countries scaling up HIV treatment

Treatment access programmes are currently expanding in resource-limited settings. The potential barriers to long-term success (such as intermittent drug supply, drug stock-outs, poor patient monitoring, incorrect prescribing practices and low adherence) as well as the need to begin programmes quickly to treat millions of individuals, have raised fears that the aggressive plan to roll out antiretroviral therapy (ART), particularly in Africa, may generate an epidemic of drug-resistant strains of HIV. Although the history of treatment programmes in developed countries suggests that some degree of resistance will inevitably develop, even if ART is appropriately provided and adherence supported, the extent of these fears may be greater than is warranted, as Blower et al. [1] explained in their recent article. We are pleased with their conclusion; however, we would like to clarify the World Health Organization (WHO) approach for the surveillance and monitoring of drug-resistant strains of HIV and factors associated with its emergence and transmission. The authors report that WHO 'is calling for wide-scale surveillance and monitoring of transmitted resistance during the rollout', and that '… sample sizes would be set in order to detect transmitted resistance if it exceeds 5% of new cases'. They concluded that the transmission rate of drug-resistant HIV will be below the surveillance threshold of 5% set by WHO and, as a consequence, the large-scale surveillance systems for detecting drug-resistant strains of HIV in Africa will be unnecessary. WHO is not recommending wide-scale surveillance as a first step for tracking drug-resistant HIV transmission, but instead a minimum-resource method called HIV Drug Resistance Threshold Survey. This method is designed for use in resource-limited countries, targeting geographical settings in which ART is already in use or is being rapidly scaled up (most likely urban settings) and where drug-resistant HIV transmission is more likely to be seen first. The HIV Drug Resistance Threshold Survey is performed by testing a limited number of eligible specimens from a recently infected population. These specimens are left over from those collected in the HIV sentinel surveys, which are conducted routinely in many resource-limited countries with generalized epidemics. The HIV Drug Resistance Threshold Survey is based on binomial sequential sampling, and up to 47 consecutively collected specimens are tested. The prevalence of resistance is not estimated precisely, but is rather classified (for each drug or drug class) as less than 5%, 5–15%, and over 15%. If prevalence is classified as less than 5% to all relevant drugs, the survey can be repeated 2 years later. If prevalence is higher, additional surveys or more resource-intensive surveillance will be required, as well as additional public health actions. In conclusion, large-scale representative HIV drug resistance surveys are recommended by WHO only for countries in which there is an indication that the prevalence of transmitted HIV drug resistance is in the higher category and resources are adequate. We also welcome the authors' suggestion that monitoring drug-resistant HIV in treated populations would be an effective approach. This is already an essential component of the new WHO HIV Drug Resistance Surveillance and Monitoring strategy, which focuses on three areas: (i) Reviewing ART clinical record analysis to examine the HIV Drug Resistance Early Warning Indicators' (such as ART prescribing practices, drug pick-up, access measures, adherence, drug supply, clinical outcomes, etc.), and to assess whether ART scale-up programmes are functioning to minimize the emergence and transmission of drug-resistant strains of HIV; (ii) Surveillance of drug-resistant HIV transmission in the ARV-naive population newly infected with HIV, to monitor whether the transmission of drug-resistant HIV has reached important levels, and to evaluate the pattern of mutations associated with resistance in transmitted strains, to support country decision-making on standard ART regimens; (iii) Monitoring of drug-resistant HIV emergence in populations starting first-line ART. These studies are to be performed at sentinel sites, with resistance testing at baseline, 12 months, and at failure or ART regimen switch. Monitoring drug-resistant strains of HIV has the objective of measuring the emergence of resistance within ART programmes; validating the HIV Drug Resistance Early Warning Indicators', and evaluating the patterns of mutations developing with various HIV subtypes and ART regimens.