Antiretroviral therapy (ART) drug resistance testing may not benefit people who have HIV in terms of mortality risk or disease progression but may improve virologic outcomes in patients who have virologic failure, according to a review published in the Cochrane Database of Systemic Reviews.
With approximately 36.7 million people living with HIV worldwide, the widespread use of ART has reduced HIV-associated mortality and morbidity. However, only 40% of patients eligible for ART are currently using it. In patients who are taking ART, drug resistance emergence poses a serious threat to a sustained virologic response to treatment and it reduces effective therapeutic options, which then may increase morbidity, mortality, and infectivity. Drug resistance can either be transmitted or acquired. Roughly 68% of patients who have received treatment with ART have experienced lack of treatment response and have developed resistance to at least 1 drug. Although the numbers are decreasing, these patients may still benefit from an earlier detection of resistance and an informed selection of ART regimen. Previous studies have demonstrated that a higher percentage of participants who have undergone resistance testing have subsequently achieved viral suppression.
Antiretroviral resistance testing is conducted in 2 ways: (1) genotypic testing sequences the viral RNA and compares it with a database of known drug resistance mutations to determine which medications it is resistant to; and (2) phenotypic testing to measure susceptibility of the virus to ART in a controlled environment exposed to specific antiretrovirals. This systemic review summarized the relative merits of resistance testing in treatment-naïve and treatment-exposed people living with HIV.
Through searches of electronic databases and conference proceedings from January 1, 1989 through January 2018, the review included all randomized controlled trials and observational studies that compared resistance testing with no resistance testing in people with HIV irrespective of their exposure to ART. A total of 11 randomized controlled trials were selected that included 2531 participants. Data on an intention-to-treat basis was analyzed using a random-effects model. In addition, subgroup analyses were performed for the type of resistance test used (phenotypic or genotypic), use of expert advice to interpret resistance tests, and age (children and adolescents vs adults). Primary outcomes of interest were mortality and virologic failure; secondary outcomes included change in mean CD4-T-lymphocyte count, clinical progression to AIDS, change in viral load, development of a second or new opportunistic infection, and quality of life.
The study results showed that resistance testing made little or no difference in mortality (odds ratio [OR] 0.89) and may have slightly reduced the number of people with virologic failure (OR 0.70). Further, resistance testing likely made little or no difference in change in CD4 cell count or progression to AIDS (OR 0.64). Resistance testing also made little to no difference in the number of adverse events experienced from medications (OR 0.89). No studies examined reported on the development of new opportunistic infections or quality of life.
These results were based on studies conducted up to 12 years ago and included very few participants from low- and middle-income countries. Overall, the study authors concluded that, “Resistance testing did not demonstrate important patient benefits in terms of risk of death or progression to AIDS.”
Aves T, Tambe J, Siemieniuk RAC, Mbuagbaw L. Antiretroviral resistance testing in HIV-positive people [published online November 9, 2018]. Cochrane Database of Systemic Reviews. doi:10.1002/14651858.CD006495.pub5