Laboratory-based survey of acquired HIV drug resistance using remnant viral load specimens
July 2, 2021
Silvia Bertagnolio,, in collaboration with Michael R. Jordan, et al.
(2021). Laboratory-based survey of acquired HIV drug resistance using remnant viral load specimens. World Health Organization. https://apps.who.int/iris/handle/10665/342053. License: CC BY-NC-SA 3.0 IGO
As antiretroviral therapy (ART) for the treatment of HIV expands, it is essential to estimate, in a standardized and nationally representative manner, the extent to which acquired HIV drug resistance emerges in populations receiving therapy. The overarching purpose of acquired HIV drug resistance surveillance is to generate a nationally representative prevalence estimate among adults (and children and adolescents) with viral non-suppression. Because the prevalence of acquired HIV drug resistance, its determinants and public health actions may differ for adults and children and adolescents, these populations are assessed separately in simultaneous surveys.
In 2014, WHO published a nationally representative survey method for assessing acquired HIV drug resistance among people receiving ART (1). This 2014 ART clinic-based survey approach uses a two-stage cluster design. The first stage consists of a random sample of ART clinics in the country where the survey is conducted; the second is a sample of patients attending the selected clinics. ART clinics are chosen using probability proportional to size sampling.
Subsequently, consecutive patients meeting the survey inclusion criteria are enrolled at sampled clinics and receive a viral load test and an HIV drug resistance test if the viral load ≥1000 copies/mL as part of the survey.
WHO recommends that viral load testing be performed early after initiating ART (within six months), at 12 months and annually thereafter to detect treatment failure (2). Patient-level HIV drug resistance genotyping is neither recommended as part of the public health model of ART delivery nor widely available in low- and middle-income countries; continuous surveillance of HIV drug resistance through analysis routine genotyping results is therefore not feasible. However, since an increasing number of people receive at least one viral load test per year, this guidance describes an approach to estimate the prevalence of acquired HIV drug resistance using routinely collected remnant viral load specimens.
Briefly, HIV drug resistance testing is conducted on a random sample of remnant viral load specimens collected from people with viral non-suppression (defined as viral load ≥1000 copies/mL1) in the context of routine viral load monitoring and stored in national viral load testing laboratories.
This method accommodates the transition to dolutegravir (DTG)-based first-line ART in most countries with a high burden of HIV infection and recognizes that the pace of transition varies by country and respects that transition to DTG-based therapies may not occur in the near future in some countries. Equally, the method acknowledges that global attention and concern is focused on the emergence of DTG resistance; thus, this method will yield robust estimates to facilitate the monitoring of trends of acquired DTG resistance over time. Simultaneously, the method yields prevalence estimates of acquired HIV drug resistance among people taking non-DTG-based regimens (such as ART based on a ritonavir-boosted protease inhibitor (PI/r) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)) and viral load suppression estimates, by regimen, since this information remains vital for strategic planning at the national, regional and global levels.