Global HIV‐1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

Abstract

Introduction HIV-1 transmitted drug resistance (TDR) in treatment-naïve individuals is a well-described phenomenon. Baseline genotypic resistance testing is considered standard of care in most developed areas of the world. Methods In the Strategic Timing of AntiRetroviral Treatment (START) trial, baseline genotypic resistance testing results were collected at study entry and analysed centrally to determine the prevalence of TDR in the study population. Resistance was based on a modified 2009 World Health Organization definition to reflect newer resistance mutations. Results Baseline resistance testing was available in 1946 study participants. Higher rates of testing occurred in Europe (86.7%), the United States (81.3%), and Australia (89.9%) as compared to Asia (22.2%), South America (1.8%), and Africa (0.1%). The overall prevalence of TDR was 10.1%, most commonly to non-nucleoside reverse transcriptase inhibitors (4.5%) and nucleoside reverse transcriptase inhibitors (4%) compared to protease inhibitors (2.8%). The most frequent TDR mutations observed were M41L, D67N/G/E, T215F/Y/I/S/C/D/E/V/N, 219Q/E/N/R, K103N/S, and G190A/S/E in reverse transcriptase, and M46I/L and L90M in protease. By country, prevalence of TDR was highest in Australia (17.5%), France (16.7%), the United States (12.6%), and Spain (12.6%). No participant characteristics were identified as predictors for the presence of TDR. Conclusion START participants enrolled in resource-rich areas of the world were more likely to have baseline resistance testing. In Europe, the United States, and Australia, TDR prevalence rates varied by country.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

“…120–122 Nonnucleoside reverse transcriptase inhibitor mutations are the most common transmitted resistance mutations (4.5%-10%); NRTI (4.0%-4.5%) and PI mutations are less common (2.8%-3.4%). 107,123 Virologic failure with an InSTI-containing regimen requires integrase resistance testing, as integrase resistance has been described in up to 6.8% of patients. 124 Resistance testing is less reliable if a patient has stopped ART for longer than 1 month when the sample is collected.…”

What does preexposure prophylaxis mean for treatment; what does treatment mean for preexposure prophylaxis?

“…This has not been seen at scale, despite over a decade of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens, which have a very low resistance barrier, being used in developing countries. Resistance occurs, and can have severe consequences for individuals, but is not yet a major public health issue, and transmitted resistance appears relatively unusual [24,25]. In South Africa, where viral load monitoring has been done since inception of the programme, and where over 3 million people (20% of the world total) are on ART (almost all on), only 200 000 are on second line, and just over 300 on third line, with surveillance programmes suggesting community resistance remains unusual, especially resistance to the drugs used for PrEP [26].…”

From policy to action: how to operationalize the treatment for all agenda

“…Use of standard packages to optimize differentiated care must be field-tested for feasibility and impact on the achievement of TfA. Successful implementation of these packages will also be dependent on 1) the placement of policies that enable task shifting; 2) the development of metrics that reflect progress towards the 90Á90Á90 and assess the impact of the differentiated package of care; 3) the existence of sufficient programmatic infrastructure, including procurement and supply chains; and 4) support of sentinel sites to monitor transmitted and acquired drug resistance and to inform future first-line ART [34] Á especially in light of growing nonnucleoside reverse-transcriptase inhibitors [35] resistance and higher-than-expected tenofovir disoproxil fumarate [36] resistance.…”