In the relentless battle against HIV, the advent of antiretroviral therapy (ART) has marked a significant turning point. The development and introduction of drug regimens have revolutionized HIV treatment, transforming HIV from a fatal illness into a manageable chronic condition. However, the dynamic nature of the virus and its ability to develop resistance to drugs necessitates continuous research into new treatment strategies.
Among the various ART regimens, Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) and Dolutegravir/Lamivudine (DTG/3TC) have become prominent choices in the United States. Both are once-daily single tablet regimens, simplifying the treatment process and enhancing adherence. This article will delve into an extensive comparative study between B/F/TAF and DTG/3TC, shedding light on their effectiveness and tolerability among HIV patients.
Background of HIV Treatment Regimens
In the realm of HIV treatment, B/F/TAF and DTG/3TC have emerged as two prominent regimens in the United States. B/F/TAF is the most prescribed regimen overall, while DTG/3TC is the most prescribed 2-drug regimen. Both regimens are composed of potent antiretroviral drugs that inhibit the replication of HIV, thus helping to control the virus in affected individuals.
These regimens are recommended as initial treatments for most people living with HIV, with the exception that B/F/TAF is also suitable for patients co-infected with hepatitis B virus (HBV). The efficacy, safety, and tolerability of these regimens have been demonstrated in several randomized controlled trials (RCTs), involving individuals who had achieved viral suppression with previous ART experience.
The Study: Objectives and Methodology
The primary objective of the comparative study was to assess and compare the risk of confirmed virologic failure and regimen discontinuation among HIV patients who switched from a prior regimen to either B/F/TAF or DTG/3TC. The study was observational and incorporated pharmaco-epidemiology research and analysis, a robust methodology that uses existing data sources to study the effects of drugs in large numbers of people.
The study’s inclusion criteria were patients aged 18 or older, who were ART-experienced, had a viral load of less than 200 copies/mL, had at least one visit to the OPERA (Observational Pharmaco-Epidemiology Research & Analysis) project, and had switched to either B/F/TAF or DTG/3TC between August 2020 and June 2022. The OPERA project encompasses approximately 14% of people with HIV in the United States, providing a large, diverse patient population for the study.
The outcomes examined in the study were confirmed virologic failure, defined as two consecutive viral loads (VLs) of 200 copies/mL or more, or one VL of 200 copies/mL or more plus discontinuation, and discontinuation, defined as any regimen modification or a treatment gap of over 45 days.
Statistical Analyses in the Study
The study used various statistical tools to analyze the collected data. A sensitivity analysis was conducted, defining confirmed virologic failure as two consecutive VLs of 50 copies/mL or more, or one VL of 50 copies/mL or more plus discontinuation. The incidence rates of virologic failure and discontinuation were calculated using Poisson regression, a type of statistical analysis suitable for data involving counts, such as the number of virologic failures.
The study also employed Cox proportional hazard models to determine the association between the regimen and time to virologic failure and discontinuation. The analyses were statistically adjusted for factors such as race, payer type, baseline CD4 cell count, and baseline estimated glomerular filtration rate (eGFR).
Results and Discussion
The study included a large cohort of 3,512 participants who switched to B/F/TAF and 2,327 who switched to DTG/3TC. The median follow-up for the B/F/TAF group was 16 months, whereas it was 15 months for the DTG/3TC group.
In terms of virologic failure, both regimens demonstrated effectiveness. Virologic failure was infrequent, and there was no statistically baseline CD4 cell count, and baseline estimated glomerular filtration rate (eGFR), which is a measure of kidney function.
Study Population and Baseline Characteristics
The study population consisted of individuals who switched to B/F/TAF (N=3,512) and those who switched to DTG/3TC (N=2,327). The median follow-up was 16 months for the B/F/TAF group and 15 months for the DTG/3TC group.
The baseline characteristics of the participants were assessed, including age, gender, race, and payer type (Medicaid or Ryan White/ADAP). Additionally, clinical characteristics such as prior regimen failure, CD4 count (a measure of immune system health), BMI (body mass index), and eGFR were also examined.
The study utilized inverse probability of treatment weights (IPTW) to achieve balance between the two groups, ensuring that differences in results were due to the treatment regimen and not confounding factors.
Risk of Confirmed Virologic Failure
The researchers analyzed the risk of confirmed virologic failure, which was defined as two consecutive viral loads (VLs) of 200 copies/mL or more, or one VL of 200 copies/mL or more plus discontinuation.
This analysis showed that both regimens were virologically effective, with infrequent virologic failure. There was no statistically significant difference between B/F/TAF and DTG/3TC in terms of virologic failure.
This result was further confirmed by a sensitivity analysis, which defined confirmed virologic failure as two consecutive VLs of 50 copies/mL or more, or one VL of 50 copies/mL or more plus discontinuation.
Risk of Regimen Discontinuation
The risk of regimen discontinuation was also assessed in the study. Discontinuation was defined as any regimen modification or treatment gap of over 45 days. The analysis indicated that discontinuation occurred statistically earlier with DTG/3TC than B/F/TAF.
Reasons for discontinuation were categorized into treatment-related reasons and other reasons. Treatment-related reasons included last VL being equal to or greater than 200 copies/mL, the occurrence of an adverse diagnosis or side effect, and lab abnormalities. Other reasons included switching to a long-acting regimen, pregnancy, access issues, a treatment gap of 45 days or more without ART, and choices made by the patient or provider. In certain cases, the reason for discontinuation was unknown.
The study’s findings shed light on the real-world use of these two prominent HIV treatment regimens. A large cohort of virologically suppressed adults in the US switched to B/F/TAF or DTG/3TC. B/F/TAF was more likely to be prescribed to Black individuals, those on Medicaid or Ryan White/ADAP, those who had experienced virologic failure on their prior regimen, those with lower CD4 cell counts, and those with higher eGFR.
Both regimens proved to be virologically effective, with infrequent virologic failure and no significant difference was observed between the two groups in terms of virologic failure.
However, the study revealed a significant difference when it came to regimen discontinuation. Discontinuation occurred statistically earlier with DTG/3TC than with B/F/TAF. More treatment-related discontinuations were observed with DTG/3TC than B/F/TAF. These treatment-related discontinuations included reasons such as last VL being equal to or greater than 200 copies/mL, the occurrence of an adverse diagnosis or side effect, and lab abnormalities.
Other reasons for discontinuation were also explored. These included switching to a long-acting regimen, pregnancy, access issues, a treatment gap of 45 days or more without ART, and choices made by the patient or provider. In certain cases, the reason for discontinuation was unknown.
Key Findings
The study uncovered several key findings. B/F/TAF was more likely to be prescribed to Black individuals, those on Medicaid or Ryan White/ADAP, those who had experienced virologic failure on their prior regimen, those with lower CD4 cell counts, and those with higher eGFR.
Despite the differences in prescription patterns, both regimens proved to be virologically effective, with infrequent virologic failure. This suggests that both B/F/TAF and DTG/3TC are viable treatment options for HIV patients. However, the study also revealed that discontinuation occurred statistically earlier with DTG/3TC than B/F/TAF. More treatment-related discontinuations were noted with DTG/3TC than B/F/TAF.
In conclusion, the findings of this study contribute to a deeper understanding of the comparative efficacy and tolerability of B/F/TAF and DTG/3TC. They can provide valuable insights for clinicians when deciding on the most suitable treatment regimen for their patients. However, it’s important to note that the choice of regimen should always be individualized to the patient, taking into account their specific needs, lifestyle, co-morbidities, and potential for drug-drug interactions.
