Dual-drug HIV treatment shines in 48-week DOLCE study results

Is antiretroviral therapy (ART) just as good with two drugs as it is with three? Newly published data from a well-constructed study give us the strongest evidence to date that, when it comes to the combination of dolutegravir and lamivudine, the answer is a ringing “Yes”—albeit with important caveats about exclusionary criteria.

Highlighted Study Population and Methods

DOLCE was a Phase 4, randomized, open-label, non-inferiority study that enrolled ART-naïve adults (age >18 years) with HIV from Argentina and Brazil. Enrolled participants had an HIV RNA > 1,000 copies/mL and CD4 cell counts < 200 cells/mm³.

There was a hefty exclusion list for this study, including people: who were pregnant or breastfeeding; who had hepatitis B virus coinfection; who had an active opportunistic infection; who had liver or renal insufficiency; or who harbored major viral resistance mutations to dolutegravir (DTG), lamivudine (3TC), or tenofovir (TDF).

In total, 230 eligible individuals were randomized 2:1 to receive DTG/3TC or DTG+TDF/XTC. (“XTC” is the commonly used abbreviation for “either 3TC or FTC”; FTC is short for the 3TC prodrug emtricitabine.) The two groups were similar in demographic characteristics:

• ~73% were male, 25% female, 2% transgender

• Median CD4 count = 116 cells/mm³

• 43% had CD4 ≤100, and 33% had CDC stage C diagnoses.T

• Median baseline viral load: 151,000 copies/mL (IQR: 49,027.5–446,947)

  • 61% >100,000 copies/mL; 23% ≥500,000 c/mL; 10% ≥1,000,000 c/mL

• HIV subtype B present in 63%

The study primary endpoint was the proportion of participants with HIV-1 RNA <50 copies/mL at week 48 (FDA Snapshot, ITT-E). Secondary endpoints included CD4 recovery, resistance in failures, and safety/tolerability.

Key Findings

Virologic suppression:

• 82% in DTG/3TC arm versus 81% in DTG+TDF/XTC arm. The adjusted difference was +2.0% (95% CI −8.7 to +12.8).

• Among people with high baseline VL (>100,000 copies/mL), the rate was 81% in the DTG/3TC arm versus 77% in the DTG+TDF/XTC arm.

CD4 recovery:

• Median +200 cells/mm³ on DTG/3TC versus +177 cells/mm³ on DTG+TDF/XTC.

Adverse events:

• Overall and serious adverse event frequency (including IRIS events) were similar in both groups.

• No emergent INSTI or NRTI resistance among virologic failures with sequences available.

Read an expert analysis from Benjamin Young, M.D., Ph.D. at TheBodyPro.