ART virological failure — DTM&H MCQ

Correct answer: D — Switch to a second-line PI-based regimen

The correct answer is D, switch to a second-line PI-based regimen. Two consecutive viral loads greater than 1000 copies/mL taken 3 months apart, with confirmed adherence support, meets the WHO definition of confirmed virological failure on a dolutegravir-based first-line regimen. Because dolutegravir has a high genetic barrier to resistance and integrase resistance is uncommon in this setting, WHO guidance directs a switch to a boosted protease inhibitor (such as atazanavir/ritonavir or lopinavir/ritonavir, with darunavir/ritonavir increasingly preferred) combined with an optimised NRTI backbone, rather than persisting with the failing integrase-inhibitor-based regimen. This reflects the standard first-line to second-line switch pathway used across sub-Saharan African ART programmes, including Mozambique, and is designed to preserve future drug options while achieving resuppression. Why the other options are wrong: C. Continue with enhanced adherence counselling: Adherence has already been confirmed, so repeating counselling alone will not address ongoing virological failure and risks accumulating resistance while the patient remains on a failing regimen. E. Switch to an NNRTI-based regimen: NNRTIs have a low genetic barrier to resistance and are not part of the WHO-recommended second-line switch after DTG failure; they offer no advantage over the current potent integrase-based regimen. A. Add a fourth drug: Simply intensifying the existing failing regimen does not address the underlying failure and is not a recognised WHO strategy for confirmed virological failure. B. Stop ART for a 4-week drug holiday: Treatment interruption is contraindicated in HIV management as it drives immune decline, opportunistic infection risk, and further selection of resistant virus. Key point: Confirmed virological failure (two viral loads greater than 1000 copies/mL despite adherence) on a dolutegravir-based first-line regimen mandates switch to a boosted PI-based second-line regimen with an optimised NRTI backbone.

Reference: World Health Organization, Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring (2021, updated recommendations), section on management of virological failure and second-line ART after dolutegravir-based first-line regimens. https://www.who.int/publications/i/item/9789240031593