Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line antiretroviral therapy in adults failing a tenofovir-based first-line regimen.

OBJECTIVE

Recycling tenofovir and lamivudine/emtricitabine (XTC) with dolutegravir would provide a more tolerable, affordable, and scalable second-line regimen than dolutegravir with an optimized nucleoside reverse transcriptase inhibitor (NRTI) backbone. We evaluated efficacy of tenofovir/lamivudine/dolutegravir (TLD) in patients failing first-line tenofovir/XTC/efavirenz or nevirapine.

DESIGN

Single arm, prospective, interventional study.

SETTING

Two primary care clinics in Khayelitsha, South Africa.

PARTICIPANTS

Sixty adult patients with two viral loads greater than 1000 copies/ml.

INTERVENTION

Participants were switched to TLD with additional dolutegravir (50 mg) for 2 weeks to overcome efavirenz induction.

PRIMARY OUTCOME

Proportion achieving viral load less than 50 copies/ml at week 24 using the FDA snapshot algorithm.

RESULTS

Baseline median CD4+ cell count was 248 cells/μl, viral load 10 580 copies/ml and 48 of 54 (89%) had resistance (Stanford score ≥15) to one or both of tenofovir and XTC. No participants were lost to follow-up. At week 24, 51 of 60 [85%, 95% confidence interval (CI) 73-93%] were virologically suppressed, six had viral load 50-100 copies/ml, one had viral load 100-1000 copies/ml, one no viral load in window, and one switched because of tenofovir-related adverse event. No integrase mutations were detected in the one participant meeting criteria for resistance testing. Virological suppression was achieved by 29 of 35 (83%, 95% CI 66-93%) with resistance to tenofovir and XTC, 11 of 13 (85%, 95% CI 55-98%) with resistance to XTC, and six of six (100%, 95% CI 54-100%) with resistance to neither.

CONCLUSION

A high proportion of adults switching to second-line TLD achieved virologic suppression despite substantial baseline NRTI resistance and most not suppressed had low-level viraemia (≤100 copies/ml). This suggests recycling tenofovir and XTC with dolutegravir could provide an effective second-line option.