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Assistant Professor, HIV Program
Department of Infectious Diseases
Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán
Mexico City, Mexico
Brenda E. Crabtree Ramirez, MD, has disclosed that she has received consulting fees from Janssen, MSD, and ViiV Healthcare.
Antiretroviral therapy (ART) with 2-drug regimens and metabolic outcomes of ART are both topics of particular interest in Latin America. Effective 2-drug regimens provide an opportunity to decrease pill burden while maintaining high rates of viral suppression. Metabolic complications of ART are of concern given that many people with HIV (PWH) develop metabolic comorbidities at a younger age, and we would like to use ART regimens that minimize this risk when possible. I am excited to share my thoughts on studies presented at IDWeek 2021 evaluating outcomes in both of those realms.
Studies 1489 and 1490: Metabolic Complications at 3 Years With First-line BIC/FTC/TAF, DTG/ABC/3TC, or DTG Plus FTC/TAF Among PWH
Comorbidities among PWH appear at a younger age and more frequently compared with their peers without HIV. Those include cardiovascular disease, diabetes, and dyslipidemia. Obesity is prevalent, especially in some regions of Latin America, and contributes to metabolic complications in PWH.
Currently, first-line ART is based on integrase strand transfer inhibitors (INSTIs), which are associated with weight gain and increased glucose levels and which may increase the risk for diabetes. Studies 1489 and 1490 are noninferiority phase III studies analyzing the incidence of metabolic changes over 144 weeks in treatment-naive patients receiving first-line ART with an INSTI-based regimen, and they compared bictegravir (BTC)/emtricitabine (FTC)/tenofovir alafenamide (TAF) with dolutegravir (DTG)-based regimens. At 144 weeks, there were no significant differences between groups for treatment-emergent diabetes, hypertension, changes in BMI, or fasting blood glucose. Surprisingly, BIC/FTC/TAF showed a greater increase in BMI through Week 96 compared with DTG/abacavir (ABC)/lamivudine (3TC), but no difference was found at 144 weeks. Changes in BMI did not differ between sex and race. Requirements of lipid-lowering therapy during the 144 weeks were similar among the 4 groups. Based on these data, this is encouraging information that INSTI-based ART, which is commonly used in Latin America, does not substantially increase one’s risk of metabolic complications.
STAT: 48-Week Results for a Rapid Test-and-Treat Approach Using DTG/3TC in Newly Diagnosed Adults With HIV
Rapid ART initiation is associated with greater retention in care and reduced time to virological suppression, as demonstrated in 2 large clinical trials in low- to middle-income countries. This is important for countries in Latin America because patients in low- to middle-income countries often present with profound immunosuppression, and it is reassuring to know that rapid initiation is effective in these patients. Dual therapy based on DTG/3TC demonstrated noninferiority efficacy, safety, and robustness to resistance in the GEMINI trials (treatment-naive patients).
The STAT study was a small pilot study evaluating DTG/3TC as a rapid test-and-treat intervention in patients newly diagnosed with HIV. The 48-week analysis focused on the efficacy of rapidly starting ART within 14 days of HIV diagnosis. From baseline to Week 48, some patients required a change from DTG/3TC to other ART because of resistance at baseline (n = 1) or hepatitis B virus (HBV) coinfection (n = 5). At 48 weeks, 2 patients met criteria for confirmed virologic failure (1 of the 2 had a baseline HIV-1 RNA of >500,000 copies/mL). Neither patient had evidence of treatment-emergent resistance, and both remained on DTG/3TC. At 48 weeks, 1 patient achieved HIV-1 RNA <50 copies/mL, and the other achieved an HIV-1 RNA of 70 copies/mL. None of the 7 patients with baseline HBV coinfection developed treatment-emergent HBV resistance to 3TC, which could have undermined the success of the rapid ART initiation.
TANGO: Week 144 Analysis of Switch to DTG/3TC vs Continued 3-Drug or 4-Drug TAF-Based Regimen
TANGO is an ongoing randomized, open-label, noninferiority phase III study evaluating the efficacy and safety of switching to DTG/3TC in virologically suppressed individuals currently receiving a 3- or 4-drug TAF-based regimen. At 144 weeks, the percentage of patients with HIV-1 RNA <40 copies/mL and target not detected in the DTG/3TC group was noninferior to remaining on a 3- or 4-drug TAF-based regimen. Confirmed virologic failure with 2 consecutive HIV-1 RNA results ≥50 copies/mL with at least one result ≥200 copies/mL was observed in 0 patients in DTG/3TC group vs 3 patients in the TAF-based group. No nucleos(t)ide reverse transcriptase inhibitor– or INSTI-associated mutations were observed at failure. Of 7 participants with preexisting archived M184V/I mutations, 4 of 4 receiving DTG/3TC and 2 of 3 receiving 3- or 4-drug TAF-based regimens had an HIV-1 RNA <50 copies/mL at their last study visit. No new safety concerns were observed through 144 weeks. The changes in weight, renal markers, and inflammatory biomarkers observed between groups were similar, and improved fasting lipids were observed with dual therapy with DTG/3TC vs 3- or 4-drug TAF-based regimens, making it an attractive option for patients wishing to streamline therapy to a 2-drug regimen without creating extra risk for developing or worsening metabolic comorbidities.
Implications for PWH in Latin America
INSTI-based regimens are used as first-line ART in Latin America and worldwide. In Latin America and in other countries, there is a need for more information and a deeper understanding of comorbidities, including weight gain associated with INSTI-based ART. The newest drug in this class is BIC, which is only available coformulated as BIC/FTC/TAF. In recent years, concerns about comorbidities associated with INSTIs in PWH have emerged. The results of the studies presented at IDWeek 2021 and described above demonstrate that BIC/FTC/TAF is a comparable option to DTG/ABC/3TC in terms of weight gain, incidence of diabetes, and incidence of hypertension and support the expansion of its use. In addition, evidence about the efficacy of longer-term use of dual therapy with DTG/3TC is becoming more and more robust, and its rapid initiation within 14 days is feasible as safe.
Will the results of these studies influence your practice and how you manage metabolic adverse events and patients receiving a 2-drug regimen? Join the discussion by posting a comment. For more details on this and other key HIV issues from IDWeek 2021, review more CCO Conference Coverage, including Capsule summary slidesets, video recaps with expert faculty, and other ClinicalThought commentaries highlighting US and global perspectives.