AIDS 2024: Efficacy of Dolutegravir/Lamivudine (DTG/3TC) in Adults with HIV-1 and Isolated Reactive Hepatitis B Core Antibody (Anti-HBc): Results From the Phase 3/3b GEMINI-1/-2, STAT, TANGO and SALSA Studies.
Speaker: Danielle Fox
Dolutegravir/Lamivudine DTG/3TC is a recommended Antiretroviral therapy (ART) regimen for individuals initiating therapy or those virologically suppressed due to its robust efficacy and high barrier to resistance. The regimen is suitable for patients with an isolated reactive Hepatitis B Core Antibody (Anti-HBc), which indicates past exposure to hepatitis B. It is applicable even if the Hepatitis B Surface Antibody (Anti-HBs) is negative. Effective management is crucial to prevent liver disease progression and mitigate the risk of hepatitis B reactivation and associated liver complications. For patients co-infected with chronic hepatitis B and Human immunodeficiency virus (HIV), additional therapy is generally recommended. A real-world study presented at the European AIDS Conference (EACS) 2023 assessed the differences in virologic suppression efficacy between individuals with a positive anti-HBc and those without past hepatitis B infection following a switch to DTG/3TC. Despite having an HIV viral load of less than 50 copies before switching, the study found lower rates of viral suppression in patients with past hepatitis B infection. It was true even when using stringent viral load measures compared to patients without a history of hepatitis B. The real-world evidence has led to a systematic analysis of randomized clinical trial data to understand better how DTG/3TC affects HIV viral suppression in individuals with prior hepatitis B exposure but lacking immunity.
The Gemini 1 and 2 studies, along with the Strategic Timing of Antiretroviral Treatment (STAT) trial, examined adults living with HIV who were naive to ART and initiated DTG/3TC, compared to the Tenofovir Alafenamide and emtricitabine with or without a boosted protease inhibitor in HIV-infected participants (TANGO) and Study to Assess the Long-term Safety and Efficacy of a Single Tablet Regimen for HIV (SALSA) studies, which involved individuals who were virologically suppressed and switched from different regimens. The post hoc analysis focused on individuals with past exposure to HIV infection and no immunity to hepatitis B. Virologic outcomes were evaluated, and 76 participants with an isolated reactive Anti-HBc were identified across the phase 3 clinical trials. Demographics were comparable between treatment groups across all studies. It is important to note that these studies did not proactively collect data on hepatitis B vaccination.
The results demonstrated high rates of virologic suppression in the DTG/3TC arm compared to DTG plus Tenofovir Disoproxil Fumarate (TDF)/ Emtricitabine (FTC), including assessments of viral loads of less than 40 copies and target being not detected. The STAT study also showed high rates of virologic suppression among its participants. Additionally, the study evaluated virologic outcomes in participants from the TANGO and SALSA studies who switched to DTG/3TC. These participants exhibited high and comparable rates of viral suppression relative to those who continued with their existing ART. Its effectiveness was observed in both the TANGO study's early and late switcharms. The findings underscore the significance of assessing the impact of different treatment regimens and the potential benefits of various treatment approaches in optimizing ART for reducing viral loads.
The safety analysis of liver chemistry tests indicated that most elevations were mild to moderate. In the Gemini 1 and 2 studies, one participant met liver-stopping criteria due to an elevation in liver enzymes related to hepatitis E and discontinued treatment at week 144. Adverse events associated with hepatitis B were reported at low rates among participants receiving DTG plus 3TC, and no cases of hepatitis B reactivation were observed in any of the studies.
The study also demonstrated that the DTG/3TC regimen for HIV treatment achieves higher rates of viral suppression, even with stringent viral load measures as seen in phase three clinical trials. Additionally, no hepatitis B reactivation was reported, highlighting the safety and efficacy of DTG/3TC for individuals with an isolated reactive Anti-HBc.
Clinical trials involving DTG and cabotegravir do not include exclusion criteria based on anti-HB status. Some studies lack data on hepatitis B activity, and additional antiviral agents are considered for individuals with active infections. In Argentina, the circumcision rate is low, with only 11% of participants circumcised. Human Papillomavirus (HPV) detection studies reveal no significant differences in HPV prevalence between circumcised and non-circumcised individuals.
The 25th International AIDS conference (AIDS 2024). 22nd-26th July, Munich, Germany
