by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer

July 28, 2020

AIDS 2020: Virtual Meeting of the 23rd International AIDS Conference, July 6-10

Below are 3 studies from AIDS 2020. The first two are from the same clinical trial – TANGO ( Identifier: NCT03446573; Clin Infect Dis. Jan 6,2020) which continue to support the efficacy of 2-drug ART for HIV patients. Based on data from the GEMINI-1 and GEMINI-2 trials (JAIDS 83;3: March 1, 2020) the current DHHS guidelines now recommend dolutegravir/lamivudine for treatment naïve HIV patients if: VL < 500,000 and there is no evidence of chronic HBV infection. The TANGO studies summarized below support both efficacy and safety of changing patients to DTG/3TC from a 3- or 4-drug regimen. It may also provide cost savings for patients whose ART is deescalated to 2-drug ART regimen. TANGO is a 144-week study, so more data will be forthcoming.

For those of us who have been treating HIV patients since the days of AZT monotherapy and then dual nucleoside therapy (which ultimately failed), it remains cognitively challenging to use only 2 drugs to treat patients. However, the data continues to become increasingly compelling and we will soon have IM cabotegravir/rilpivirine as another dual therapy option.

Comparison of viral replication at <40c/mL for the 2-drug regimen of dolutegravir/lamivudine (DTG/3TC) versus a 3-drug regimen-based with tenofovir alafenamide (TAF) in the TANGO study. Wang R. Abstract PEB0238.

The TANGO study showed that switching to the 2-drug regimen of DTG/3TC from a 3-drug regimen was non-inferior in regards to maintaining viral suppression (VL< 50c/ml). This study of patients from TANGO used the Abbott RealTime PCR assay which measures HIV-1 viral loads from 40 copies to 10 million copies/mL. The assay also provides a qualitative target detected (TD) or target not detected (TND) outcome for those with a VL<40 copies/mL. This study assessed the number of subjects with TD or TND through Week-48 in Tango – comparing the DTG/3T patients with those taking 3-drugs. At week-48, 79% of subjects in the 2-drug arm and 76% in the 3-drug arm had TND for a VL < 40 c/mL. Of participants with TND at baseline, the proportion with TND at all follow-up visits through week-48 was 53% in 2-drug and 46% in the 3-drug arm. This study concludes that post-baseline incident viremia (>=40c/mL) was more often associated with baseline TD than baseline TND. However, when using the strict TND threshold there was NO difference in the number of subjects with detectable viremia at week-48 of TANGO whether they were taking 2-drugs or 3-drugs.


Improved metabolic parameters after switching from TAF-based 3- or 4-drug regimen to the 2-drug regimen of DTG/3TC (dolutegravir/lamivudine): The TANGO study. Van Wyk J. OAB0606

Primary outcomes from the TANGO study demonstrated that switching to DTG/3TC is non-inferior at 48 weeks to continuing a 3 or 4-drug TAF-based regimen in suppressed patients. However, switching from TDF to TAF or using boosting agents has been associated with weight gain and dyslipidemia. This study of TANGO participants summarizes changes over 48 weeks in regards to fasting glucose and insulin levels, A1C, lipid levels, the prevalence of metabolic syndrome, and weight gain. Most participants were male (92%) with a median age of 40 years. Changes in fasting glucose and A1C levels were minimal across arms although changes in fasting insulin favored the DTG/3TC arm. Changes in lipids, including TC:HDL ratio, favored the DTG/3TC group compared to those on a TAF or a boosted ART regimen. Those diagnosed with metabolic syndrome included 11% in the DTG/3TC and 12% in the TAF-based patients. Regarding weight gain, this was similar at 0.81kg (DTG/3TC) and 0.76 kg (3-drug). The authors conclude that switching from 3 or 4-drug TAF-based regimens to DTG/3TC led to similar increases in weight, but with improvements in other metabolic parameters that are clinically important.

Comparative efficacy and safety of a combination therapy of dolutegravir and lamivudine vs 3-drug antiretroviral regimens in treatment-naïve HIV-1 infected patients at 96 weeks: A systematic review and network meta-analysis. Nickel K, et al. Abstract PDB0104

This study compared the efficacy and safety of DTG/3TC to other 3-drug guideline-recommended ART regimens for up to 96 weeks. The authors performed a systematic review of 11 randomized controlled trials two versus three drug ART in treatment-naïve HIV-1 patients (n=7997). The proportion of patients with baseline viral loads of > 100,000 copies/ml and attained virologic suppression to <50 RNA copies/mL was compared between DTG+3TC and other DHHS recommended ART regimens. Other outcomes studied were CD4+ cell count changes from baseline, treatment discontinuations, and adverse events. Treatment differences for viral suppression at 96 weeks for DTG/3TC compared to the other ART regimens were similar, ranging from -3% vs DTG+TDF (or) TAF/FTC to 13% compared to ritonavir-boosted darunavir + TDF/FTC. Regarding other outcomes DTG+3TC was similar to all 3-drug ARTs. Mean changes in CD4 counts were significantly higher from baseline in the DTG/3TC group compared to five of the other ART regimens. There were significantly fewer drug-related and serious adverse events in the DTG/3TC patients. The authors conclude that DTG+3TC offers comparable efficacy and safety to 3-drug regimen in treatment naïve patients.


The author has no conflicts of interest to disclose.

View archived Clinical Research Update entries here.