ABSTRACT
INTRODUCTION: Dolutegravir/lamivudine (DTG/3TC) and dolutegravir/rilpivirine (DTG/RPV) are fixed-dose, complete, single-tablet, two-drug regimens (2DRs) indicated for HIV-1. DTG/3TC is approved for antiretroviral therapy (ART)-naive people with HIV-1 and virologically suppressed individuals to replace current ART; DTG/RPV is indicated for virologically suppressed individuals as a switch option. Virologic efficacy and effectiveness of these DTG-based 2DRs have been demonstrated in phase 3 clinical trials and real-world cohorts, primarily from Europe. This study characterized real-world use of DTG-based 2DRs for HIV-1 treatment in the USA. METHODS: TANDEM was a retrospective medical chart review across 24 US sites. Individuals aged ≥ 18 years who initiated DTG/3TC or DTG/RPV before September 30, 2020, with ≥ 6 months of follow-up were included. One cohort included ART-naive people who initiated DTG/3TC (n = 126), and two other cohorts included virologically suppressed (HIV-1 RNA < 50 copies/mL) people on stable ART regimens for ≥ 3 months before switch to either DTG/3TC (n = 192) or DTG/RPV (n = 151). Clinical characteristics, treatment history, and outcomes are described. RESULTS: Virologically suppressed individuals were older than those who were ART-naive, and the ART-naive cohort had higher proportions of individuals assigned male at birth and of Hispanic ethnicity. The most common healthcare provider-reported reason for choosing a DTG-based 2DR was avoidance of long-term toxicities (25-33% across cohorts), followed by simplification/streamlining of treatment. Among ART-naive people on DTG/3TC, 94% achieved virologic suppression after initiation, and 83% maintained suppression at last follow-up; discontinuation rate was < 1%. Among cohorts who switched to DTG-based 2DRs, 96% maintained virologic suppression on DTG/3TC and 93% on DTG/RPV; 2% on DTG/3TC and 3% on DTG/RPV discontinued. CONCLUSION: Motivation for selecting DTG-based 2DRs was primarily driven by a desire to avoid or manage toxicities and simplify treatment. Results demonstrate that DTG/3TC and DTG/RPV are effective in real-world settings, with few discontinuations, reflecting data from clinical trials.
ABSTRACT
INTRODUCTION: Dolutegravir/lamivudine (DTG/3TC) was first approved by the US Food and Drug Administration in 2019 for the treatment of antiretroviral therapy (ART)-naive people with HIV-1 based on results from the pivotal GEMINI-1/GEMINI-2 trials. Around that time, immediate initiation of treatment upon diagnosis was recommended in the US Department of Health and Human Services guidelines. Here we report results from 126 treatment-naive people with HIV-1 who initiated DTG/3TC as part of a test-and-treat strategy (n = 61) or with high baseline viral loads (HIV-1 RNA ≥ 100,000 copies/ml; n = 16) from the TANDEM study. METHODS: TANDEM was a US-based, retrospective chart review study that included a cohort of 126 individuals aged ≥ 18 years with no prior history of ART who initiated DTG/3TC before September 30, 2020, and had ≥ 6 months of follow-up. Test-and-treat was defined as ART initiation shortly after diagnosis without available viral load, CD4 + cell count, or HIV-1 resistance data. Outcomes included virologic suppression (HIV-1 RNA < 50 copies/ml; overall and by baseline viral load) and discontinuations. Analyses were descriptive. RESULTS: Among 61 individuals who initiated DTG/3TC in a test-and-treat setting (median [interquartile range (IQR)] treatment duration, 1.3 [0.9-1.7] years), 57 (93%) achieved virologic suppression, and 51 (84%) remained suppressed; 1 (< 1%) individual discontinued DTG/3TC due to persistent low-level viremia. The most common healthcare provider (HCP)-reported reason for initiating DTG/3TC was avoidance of long-term toxicities among individuals in the test-and-treat subgroup. Of 16 treatment-naive individuals with high baseline viral loads (median [IQR] treatment duration, 100,000-250,000 copies/ml: 1.2 [0.8-1.8] years; > 250,000 copies/ml: 1.0 [0.7-1.1] years), 14 (88%) achieved virologic suppression, 13 (81%) remained suppressed, and none discontinued DTG/3TC. Patient preference was the most common HCP-reported reason for initiating DTG/3TC in this subgroup. CONCLUSIONS: Results demonstrate real-world effectiveness of DTG/3TC, with few discontinuations, in people with HIV-1 in test-and-treat settings or with high baseline viral loads.
ABSTRACT
OBJECTIVE: Cabotegravir long-acting (CAB-LA) administered every 2 months was approved in the USA as pre-exposure prophylaxis (PrEP) for individuals at risk of acquiring human immunodeficiency virus (HIV)-1 infection based on the HIV Prevention Trials Network (HPTN) 083 and HPTN 084 clinical trials, which demonstrated superior reduction in HIV-1 acquisition compared with daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in men who have sex with men (MSM), transgender women (TGW), and cisgender women. A decision-analytic model was developed to assess the lifetime cost-effectiveness of initiating CAB-LA versus generic oral FTC/TDF for HIV PrEP in the USA from a healthcare sector perspective. METHODS: PrEP-eligible adults entered the Markov model receiving CAB-LA or FTC/TDF and could continue initial PrEP, transition to a second PrEP option, or discontinue PrEP over time. Efficacy was taken from the HPTN 083 and HPTN 084 clinical trials. Individuals who acquired HIV-1 infection incurred lifetime HIV-related costs, could transmit HIV onwards, and could develop PrEP-related resistance mutations. Input parameter values were obtained from public and published sources. Model outcomes were discounted at 3%. RESULTS: The model estimated that the CAB-LA pathway prevented 4.5 more primary and secondary HIV-1 infections per 100 PrEP users than the oral PrEP pathway, which yielded 0.2 fewer quality-adjusted life-years (QALYs) lost per person. Additional per-person lifetime costs were $9476 (2022 US dollars), resulting in an incremental cost-effectiveness ratio of $46,843 per QALY gained. Results remained consistent in sensitivity and scenario analyses, including in underserved populations with low oral PrEP usage. CONCLUSIONS: Our analysis suggests that initiating CAB-LA for PrEP is cost-effective versus generic daily oral FTC/TDF for individuals at risk of acquiring HIV-1 infection.
