Examining the cost-effectiveness and efficacy of combination therapies in HIV

An estimated 1.2 million people live with HIV in the United States. The annual direct spending for HIV/AIDS treatment is $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 The bronze poster award was received by AMCP. Researchers assessed the health care costs and utilization (HCRU), during antiretroviral treatment for PLWH switching from guideline recommmended INSTI with one or two nuceloside reverse transcriptase inhibiters (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.

An administrative claims database was used to perform a retrospective cohort analysis. This data covered 4251 Medicare Advantage and commercial health plans that enrolled adults in Optum Research Database between January 1, 2010 and March 31, 2020. The mean age of the patients was 52.3 years. The mean Charlson score was 58.4%. The majority of patients were men (84.1%), had insurance (65.9%), and resided 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, ABC/3TC/DTG and FTC/TAF+DTG were cited to be INSTI-based single-tablet regimens. FTC/TAF+DTG was an INSTI-based multitablet regimen. FTC/TDF+DTG and FTC/TAF+DTG were INSTI based multi-tablet regimens.

Multiple metrics were used for the examination of the primary end points.

• Health care resource usage: All-cause utilization and HIV-related utilization were calculated per month for ambulatory (office and outpatient), emergency room (ED) visits, inpatient stays, pharmacy fills and other health care services.
• Health care costs: All-cause and HIV-related costs were adjusted to 2019 US Dollars and calculated as the PPPM summation of patient and health plan paid amounts, including pharmacy and medical costs (ambulatory and ED hospitalization). [IP](and other medical expenses)
• If the costs included a diagnosis or a defining condition such as HIV (eg, lymphoma) or pneumonia, they were considered HIV-related.

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 accounting for covariates with the IPTW, it was found that monthly mean (SD) medical expenses were similar between triple INSTI-based INSTI-based regimens of B/FTC/TAF $699 (33602), ABC/3TC/DTG 770 ($3469), FTC/TAF+DTG 817 ($3128), FTC/TAF+DTG $817 (33128), FTC/TDF+DTG $3570 ($17.691)

The costs for ambulatory visits and IP stays were similar across all 4 cohorts. However, researchers noted that there were differences in baseline variables such as Charlson’s comorbidity index and renal dysfunction.

After accounting for the baseline measures left after IPTW through multivariable stepwise analyses, HIV-related costs were lowest for patients receiving INSTI-based singletable regimens. Comparable to B/FTC/TAF HIV-related medical expenses were 20% higher for ABC/3TC/DTG (cost ratio of 1.20; 95%CI, 0.851-1.694) P =.299), 49% more for FTC/TAF+DTG; cost ratio, 1.489; 95%CI, 1.018-2.179 P =.040), nearly 11 times higher for FTC/TDF+DTG; cost ratio, 10.759; 95%CI, 2.182-53.248; P = .004).

In addition, patients with a Charlson Comorbidity Score of 3 or more or with evidences of substance abuse and polypharmacy had significantly higher HIV -related medical expenses. Patients with lower baseline all cause health care costs had significantly lower HIV related medical costs.

Researchers noted that PLWH were primarily covered by commercial insurance. This means that results could differ for Medicare and Medicaid populations. The study’s limitations were also noted as the South-focused geographic focus and small sample size for the FTC/TDF+DTG cohort.

“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

Lenacapavir, a first-in-class, long-acting inhibitor of capsid function was developed for the treatment and prevention HIV-1. It was evaluated in the second poster for its safety and efficacy in long-term 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. The CALIBRATE study’s findings will be used to generate exploratory clinical information for the development of lenacapavir-containing regimens in the future, according to noted researchers. The December 27, 2022 Prescription Drug User Fee Act (PDUFA), action date for lenacapavir has been set.

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, while TG4 (n=25) received oral once daily B/F/TAF. There were no prespecified formal statistical analyses between the treatment groups.

The median age in the study cohort was 29. 15% had a viral load greater than 100,000c/mL. According to FDA Snapshot algorithm, week 28 results showed that 94% of the 4 treatment groups had a VL lower than 50 c/mL.

Comparative results at week 54 showed that 90%, 85% and 85% had VLs less than 50 c/mL. The majority of those who received lenacapavir from TG1 to TG3 had either stopped taking the study drug or had VLs below 50 c/mL by week 54.

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

None of the participants experienced an adverse event (AE) related to study drug. 3 participants of TG2 had to stop treatment because of injection site reactions (ISR). ISRs were of erythema (27%), swelling (23%), pain (19%), which were mostly mild-to-moderate in the TG1 to TG3 groups. The most common non-ISR AEs reported in TG1 to TG3 were headache and nausea (13%).

Researchers concluded that lenacapavir is being evaluated as an oral and injectable form of HIV-1 treatment for individuals with different needs.

Refer to

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 20,22; October 11-14th, 2022; National Harbor MD. Abstract B2.

2. Carter M, Gupta S, Oguchi G, et al. Week 54 Results: Lenacapavir in a Combination Treatment Regimen in Treatment-Naive HIV-Naive People: Presented at: AMCP Nexus 20, 22 October 2011-14, 2022; National Harbor MD. Abstract B6.