Dolutegravir Plus Lamivudine Two-Drug Regimen: Safety, Efficacy and Diagnostic Considerations for Its Use in Real-Life Clinical Practice-A Refined Approach in the COVID-19 Era

Abstract

The diagnostic and therapeutic management of the Coronavirus Disease 2019 (COVID-19) pandemic in the HIV population brought some known criticalities (and opportunities) to the forefront, for both those who are facing their first therapeutic line today, and for those already well viro-suppressed. The clinical, socioeconomic, and psychological impact of the COVID-19 pandemic should not affect the long-term care of people living with HIV, which creates an urgent need to optimize the diagnostic and treatment approach to the first-line or switch regimens. The use of dolutegravir plus a lamivudine two-drug regimen is one of the most promising solutions to ease the management of HIV treatment in this difficult period. In this review, we report the most salient features related to the use of this regimen from real-life cohorts, meta-analyses, randomized clinical trials, and studies presented at international conferences up to March 2021. We focused on the diagnostic and clinical-management implications of its use in real life, and how these comply with the contingent historical situation. The issue of the timing and type of diagnostic procedures and the relevance of classical diagnostic tests (such as genotype for resistance detection) is also discussed. According to the currently available results, dolutegravir plus a lamivudine two-drug regimen represents an outstanding tool, whose expected advantages fulfill the current requirements for optimal daily care of our HIV patients.

Keywords: HIV drug-resistance; archived resistance; drug-naïve; dual therapy; integrase strand transfer inhibitor; treatment simplification.

Figure 1

Dolutegravir plus lamivudine two- and three-drug regimens in treatment-naïve patients. (a) Efficacy in randomized clinical trials by FDA snapshot analysis at week-144. Histograms represent individual studies—not a head-to-head comparison. (b) Efficacy of dolutegravir plus lamivudine in GEMINI-1 and GEMINI-2 randomized clinical trials by FDA snapshot analysis at week-144, in patients with baseline viral load >100,000 copies/mL, and in patients with baseline CD4 cell count <200 copies/mL. (c) Efficacy of dolutegravir plus lamivudine in URBAN real-life study, week-24 result in the effectiveness set (excluding missing data). 3TC = lamivudine; ABC = abacavir; BIC = bictegravir; BL = baseline; DTG = dolutegravir; EFV = efavirenz; FTC = emtricitabine; NI = noninferior treatment difference; ns = not statistically significant difference; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate.

Figure 2

96-week intention-to-treat efficacy of two-drug regimens in virologically suppressed patients in clinical trials. Histograms represent individual studies—not a head-to-head comparison. 3TC = lamivudine; ATV/r = ritonavir-boosted atazanavir; cART = combination antiretroviral therapy; DTG = dolutegravir; DRV/r = ritonavir-boosted darunavir; NI = noninferior treatment difference; RPV = rilpivirine; TAF = tenofovir alafenamide.

Figure 3

Achievement and maintenance of non-detectable viral-load values in patients enrolled in dolutegravir-based two-drug regimens clinical trials. Histograms represent individual studies—not a head-to-head comparison. (a) Proportion of drug-naïve participants with TND values by week of treatment from GEMINI-1 and -2 studies (snapshot analysis). (b) Proportion of treatment-experienced participants with TND values by week of treatment from the TANGO study (snapshot analysis). (c) Proportion of TND values by week of treatment for treatment-experienced participants with TND at baseline, from the SWORD-1 and SWORD-2 studies. 3TC = lamivudine; cART = combination antiretroviral therapy; DTG = dolutegravir; FTC = emtricitabine; RPV = rilpivirine; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TND = Target not detected.