Examining Cost-effectiveness, Efficacy of Combination Therapies in HIV

There are an estimated 1.2 million people living with HIV (PLWH) in the United States, with total annual direct expenditures for HIV/AIDS treatment and care amounting to $10.7 billion. Two posters presented at the Academy of Managed Care Pharmacy (AMCP) Nexus 2022 meeting sought to investigate the cost-effectiveness of guideline recommended integrase strand transfer inhibitor (INSTI)–based triple therapy in patients with HIV-1, as well as the efficacy of adjuvant lenacapavir in treatment-naïve individuals.

For the first poster,¹ which received a bronze poster award from AMCP, researchers assessed the health care cost and utilization (HCRU) during lines of antiretroviral (ARV) treatment for PLWH switching to guideline recommmended INSTI in combination with one or 2 nuceloside reverse transcriptase inhibitors (NRTIs).

INSTI-based ARV regimens are better tolerated and associated with few drug-drug interactions and discontinuation compared with boosted protease inhibitor–based and non-nucleoside reverse transcriptase inhibitor–based regimens, they noted, but little is known regarding the economic burden of treatment experienced PLWH switching to these triple therapies.

“It was anticipated that in a switch population, patients with differing severity and intensity of resource needs will be channeled unequally between therapies; therefore, it was necessary to utilize statistical techniques such as inverse probability treatment weighting (IPTW) and general linear model comparisons with covariate adjustment to control for as many baseline differences as possible,” explained researchers.

A retrospective cohort analysis was conducted by using administrative claims data for a total of 4251 commercial and Medicare Advantage health plan enrolled adults in the Optum Research Database between January 1, 2010, and March 31, 2020 (mean age, 52.3 years; mean Charlson comorbidity score). A majority of patients were male (84.1%), had commercial insurance (65.9%), and lived in the South (58.4%)

HIV-related HCRU from the health plan and patient perspective were examined by site of service and compared between INSTI-based triple regimens: bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF) (n = 2727; 64.2%) vs abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) (n = 898; 21.1%), FTC/TAF+DTG (n = 539; 12.7%), and FTC/tenofovir (TDF)+DTG (n = 87; 2.1%). B/FTC/TAF and ABC/3TC/DTG were cited as INSTI-based single tablet regimens whereas FTC/TAF+DTG and FTC/TDF+DTG were INSTI-based multi-tablet regimens.

Several metrics were used to examine the primary end points:

• Health care resource utilization: all-cause and HIV-related utilization were calculated per patient per month for ambulatory visits (office and outpatient), emergency department (ED) vists, inpatient stays, and pharmacy fills
• Health care costs: all-cause and HIV-related health care costs were adjusted to 2019 US dollars and computed as the PPPM sum of health plan and patient paid amounts, including pharmacy costs and medical costs (ambulatory, ED, inpatient hospitalization [IP], and other medical costs)
• Costs were considered HIV-related if they included a diagnosis of HIV or an AIDS-defining condition (eg, lymphoma or pneumonia)
  

The first line of therapy during the study period for treatment-experienced adults switching to guideline recommended INSTI triple therapies was also included in the analysis.

After adjusting for covariates with IPTW, mean (SD) medical costs per month were shown to be similar between the INSTI-based triple regimens of B/FTC/TAF $699 ($3602), ABC/3TC/DTG $770 ($3469), FTC/TAF+DTG $817 ($3128), and FTC/TDF+DTG $3570 ($17,691).

Costs for ambulatory visits, IP stays, and ED visits were also similar across each of the 4 cohorts, though researchers noted that differences remained for baseline variables such as Charlson comorbidity index, renal dysfunction, and all-cause health care cost.

After further controlling for baseline measures remaining after IPTW via multivariable stepwise analysis, HIV-related medical costs were lowest for patients treated with INSTI-based single table regimens. Compared with B/FTC/TAF, HIV-related medical costs were 20% numerically higher for ABC/3TC/DTG (cost ratio, 1.20; 95% CI, 0.851-1.694; P = .299), 49% higher for FTC/TAF+DTG (cost ratio, 1.489; 95% CI, 1.018-2.179; P = .040), and nearly 11 times greater for FTC/TDF+DTG (cost ratio, 10.759; 95% CI, 2.182-53.048; P = .004).

The follow-up period additionally showed that patients with a Charlson comorbidity score of 3 or more or those with evidence of substance abuse and polypharmacy had significantly higher HIV-related medical costs. Significantly lower HIV-related medical costs were also found among patients with lower baseline all-cause health care costs.

As PLWH were primarily covered with commercial insurance, researchers said that results may differ for Medicaid and Medicare populations. The geographic focus on the South and the small sample size of the FTC/TDF+DTG cohort were also cited as limitations of the study.

“Overall, PLWH who are treated with guideline recommended INSTI-based triple therapy experienced a significant economic burden,” concluded the study authors. “Selecting the appropriate treatment regimen may help patients maintain lower health care costs.”

54-Week Results of Lenacapavir Combination Regimen in Treatment-Naïve PLWH

In development for treatment and prevention of HIV-1, lenacapavir, a long-acting first-in-class inhibitor of capsid function, was examined in the second poster for its long-term efficacy and safety in treatment-naive PLWH.²

The ongoing, open-label, phase 2 CALIBRATE study evaluating subcutaneous (SC) and oral lenacapavir, in combination with emtricitabine/tenofovir alafenamide (F/TAF), has previously demonstrated high rates of virologic suppression (94%) at 28 weeks. Findings of the CALIBRATE study serve to generate exploratory clinical data for the potential future development of lenacapavir containing regimens, noted researchers. A Prescription Drug User Fee Act (PDUFA) action date for lenacapavir is currently set for December 27, 2022.

A total of 182 treatment-naïve PLWH (7% female; 52% Black) part of the CALIBRATE study were randomized (2:2:2:1) to 1 of 4 treatment groups (TG). TG1 (n = 52) and TG2 (n = 53) received SC lenacapavir plus oral daily F/TAF for 28 weeks, after which virologically-suppressed participants continued a 2-drug maintenance regimen: SC lenacapavir with once-daily TAF (TG1) or once-daily B [bictegravir] (TG2). TG3 (n = 52) received oral once-daily lenacapavir plus F/TAF and TG4 (n = 25) received oral once-daily B/F/TAF throughout. No prespecified formal statistical comparisons were conducted between treatment groups.

Among the study cohort, median age was 29 years and 15% had viral load (VL) greater than 100,000 c/mL. As previously reported, week 28 findings showed that 94%, 92%, 94%, and 100% of the 4 treatment groups had VL less than 50 c/mL by FDA Snapshot algorithm.

Findings at week 54 comparitvely showed that 90%, 85%, 85%, and 92% had VL less than 50 c/mL. For the groups who received lenacapavir (TG1 to TG3), the majority of the remaining participants had discontinued the study drug or achieved VL less than 50 c/mL later.

Among those with VL less than 50 c/mL at week 28, starting the 2-drug maintenance regimen in TG1 and TG2 resulted in 94% and 92% achieving VL less than 50 c/mL at week 54. Moreover, for participants in TG1 to TG3, CD4 count increased by a median of 219 cells/µL at week 54 vs TG4.

No participant experienced a study drug-related serious adverse event (AE). Injection site reactions (ISR) led to 3 participants of TG2 to discontinue treatment, with ISRs of erythema (27%), swelling (23%), and pain (19%) reported in groups TG1 to TG3, which were mostly mild or moderate. In TG1 to TG3, the most frequent non-ISR AEs were headache and nausea (13% each).

Researchers concluded that the results support ongoing evaluation of lenacapavir, as both injectable and oral formulations, in combination with other antiretroviral agents for the treatment of HIV-1 infection in individuals with diverse needs.

References

1. Rock M, Anderson A, Webb N, et al. Health care cost and utilization among treatment-experienced patients with HIV switching to an INSTI-based guideline recommended triple therapy since 2018. Presented at: AMCP Nexus 2022; October 11-14, 2022; National Harbor, MD. Abstract B2.

2. Carter M, Gupta S, Oguchi G, et al. Lenacapavir as part of a Combination Regimen in Treatment-Naive People with HIV: Week 54 Results. Presented at: AMCP Nexus 2022; October 11-14, 2022; National Harbor, MD. Abstract B6.