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Cost-Effectiveness of Three Alternative Boosted Protease Inhibitor-Based Second-Line Regimens in HIV-Infected Patients in West and Central Africa.

ABSTRACT: BACKGROUND:While dolutegravir has been added by WHO as a preferred second-line option for the treatment of HIV infection, boosted protease inhibitor (bPI)-based regimens are still needed as alternative second-line options. Identifying optimal bPI-based second-line combinations is essential, given associated high costs and funding constraints in low- and middle-income countries. We assessed the cost-effectiveness of three alternative bPI-based second-line regimens in Burkina Faso, Cameroon and Senegal. METHODS:We used data collected over 2010-2015 in the 2LADY trial/post-trial cohort. Patients with first-line antiretroviral therapy (ART) failure were randomly assigned to tenofovir/emtricitabine?+?lopinavir/ritonavir (TDF/FTC LPV/r; arm A), abacavir?+?didanosine?+?lopinavir/ritonavir (arm B), or tenofovir/emtricitabine?+?darunavir/ritonavir (arm C). Costs (US dollars, 2016), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were computed for each country over 24 months of follow-up and extrapolated to 5 years using a simulated patient-level Markov model. We assessed uncertainty using cost-effectiveness acceptability curves, scenarios and prices threshold analysis. RESULTS:In each country, over 24 months, arm A was significantly less costly than arms B and C (incremental costs ranging from US$410-$US721 and US$468-US$546 for B and C vs A, respectively) and offered similar health benefits (incremental QALY: -?0.138 to 0.023 and -?0.179 to 0.028, respectively). Over 5 years, arm A remained the least costly, health benefits not being significantly different between arms. Compared with arms B and C, in each study country, Arm A had a???95% probability of being cost-effective for a large range of cost-effectiveness thresholds, irrespective of the scenario considered. CONCLUSIONS:Using TDF/FTC LPV/r as a bPI-based second-line regimen provided the best economic value in the three study countries. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT00928187.

SUBMITTER: Boyer S

PROVIDER: S-EPMC7018873 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Cost-Effectiveness of Three Alternative Boosted Protease Inhibitor-Based Second-Line Regimens in HIV-Infected Patients in West and Central Africa.

Boyer S S Nishimwe M L ML Sagaon-Teyssier L L March L L Koulla-Shiro S S Bousmah M-Q MQ Toby R R Mpoudi-Etame M P MP Ngom Gueye N F NF Sawadogo A A Kouanfack C C Ciaffi L L Spire B B Delaporte E E

PharmacoEconomics - open 20200301 1

<h4>Background</h4>While dolutegravir has been added by WHO as a preferred second-line option for the treatment of HIV infection, boosted protease inhibitor (bPI)-based regimens are still needed as alternative second-line options. Identifying optimal bPI-based second-line combinations is essential, given associated high costs and funding constraints in low- and middle-income countries. We assessed the cost-effectiveness of three alternative bPI-based second-line regimens in Burkina Faso, Cameroo ...[more]

PMID: 31273686

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Project description:WHO recommends ritonavir-boosted protease inhibitor with two nucleoside reverse transcriptase inhibitors in HIV-infected patients failing non-nucleoside reverse transcriptase inhibitor-based first-line treatment. Here, we aimed to provide more evidence for the choice of nucleoside reverse transcriptase inhibitor and boosted protease inhibitor.ANRS 12169 is a 48-week, randomized, open-label, non-inferiority trial in three African cities, comparing efficacy and safety of three second-line regimens.Patients failing non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy with confirmed plasma HIV-1 viral load above 1000?copies/ml were randomly assigned to tenofovir/emtricitabine + lopinavir/ritonavir (control group as per WHO recommendations), abacavir + didanosine + lopinavir/ritonavir (ABC/ddI group) or tenofovir/emtricitabine + darunavir/ritonavir (DRV group) regimens. The primary endpoint was the proportion of patients with plasma vral load below 50?copies/ml at week 48 in the modified intention-to-treat population. Non-inferiority was pre-specified with a 15% margin.Of the 454 randomized patients, 451 were included in the analysis. Globally, 294 (65.2%) and 375 (83.2%) patients had viral load below 50 and 200?copies/ml, respectively, at week 48. The primary endpoint was achieved in 105 (69.1%) control group patients versus 92 (63.4%) in the ABC/ddI (difference 5.6%, 95% confidence interval -5.1 to 16.4) and 97 (63.0%) in the DRV (difference 6.1%, 95% confidence interval -4.5 to 16.7) groups (non-inferiority not shown). Overall, less number of patients with baseline viral load at least 100?000?copies/ml (n?=?122) had a viral load below 50?copies/ml at week 48 (37.7 versus 75.4%; P?<?0.001).The three second-line regimens obtained similar and satisfactory virologic control and confirmed the WHO recommendation (TDF/FTC/LPVr) as a valid option. However, the suboptimal response for patients with high viral load warrants research for improved strategies.

Project description:Pygmy Chameleons of the genus Rhampholeon represent a moderately diverse, geographically circumscribed radiation, with most species (18 out of 19 extant taxa) limited to East Africa. The one exception is Rhampholeon spectrum, a species restricted to West-Central African rainforests. We set out to characterize the geographic basis of genetic variation in this disjunctly distributed Rhampholeon species using a combination of multilocus Sanger data and genomic sequences to explore population structure and range-wide phylogeographic patterns. We also employed demographic analyses and niche modeling to distinguish between alternate explanations to contextualize the impact of past geological and climatic events on the present-day distribution of intraspecific genetic variation. Phylogenetic analyses suggest that R. spectrum is a complex of five geographically delimited populations grouped into two major clades (montane vs. lowland). We found pronounced population structure suggesting that divergence and, potentially, speciation began between the late Miocene and the Pleistocene. Sea level changes during the Pleistocene climatic oscillations resulted in allopatric divergence associated with dispersal over an ocean channel barrier and colonization of Bioko Island. Demographic inferences and range stability mapping each support diversification models with secondary contact due to population contraction in lowland and montane refugia during the interglacial period. Allopatric divergence, congruent with isolation caused by geologic uplift of the East African rift system, the "descent into the Icehouse," and aridification of sub-Saharan Africa during the Eocene-Oligocene are identified as the key events explaining the population divergence between R. spectrum and its closely related sister clade from the Eastern Arc Mountains. Our results unveil cryptic genetic diversity in R. spectrum, suggesting the possibility of a species complex distributed across the Lower Guinean Forest and the Island of Bioko. We highlight the major element of species diversification that modelled today's diversity and distributions in most West-Central African vertebrates.

Project description:The South African national combination antiretroviral therapy (cART) roll-out program started in 2006, with over 4.4 million people accessing treatment since it was first introduced. HIV-1 drug resistance can hamper the success of cART. This study determined the patterns of HIV-1 drug-resistance associated mutations (RAMs) in People Living with HIV-1 (PLHIV-1). Receiving first (for children below 3 years of age) and second-line (for adults) cART regimens in South Africa. During 2017 and 2018, 110 patients plasma samples were selected, 96 samples including those of 17 children and infants were successfully analyzed. All patients were receiving a boosted protease inhibitor (bPI) as part of their cART regimen. The viral sequences were analyzed for RAMs through genotypic resistance testing. We performed genotypic resistance testing (GRT) for Protease inhibitors (PIs), Reverse transcriptase inhibitors (RTIs) and Integrase strand transfer inhibitors (InSTIs). Viral sequences were subtyped using REGAv3 and COMET. Based on the PR/RT sequences, HIV-1 subtypes were classified as 95 (99%) HIV-1 subtype C (HIV-1C) while one sample as 02_AG. Integrase sequencing was successful for 89 sequences, and all the sequences were classified as HIV-1C (99%, 88/89) except one sequence classified CRF02_AG, as observed in PR/RT. Of the 96 PR/RT sequences analyzed, M184V/I (52/96; 54%) had the most frequent RAM nucleoside reverse transcriptase inhibitor (NRTI). The most frequent non-nucleoside reverse transcriptase inhibitor (NNRTI) RAM was K103N/S (40/96, 42%). Protease inhibitor (PI) RAMs M46I and V82A were present in 12 (13%) of the sequences analyzed. Among the InSTI major RAM two (2.2%) sequences have Y143R and T97A mutations while one sample had T66I. The accessory RAM E157Q was identified in two (2.2%). The data indicates that the majority of the patients failed on bPIs didn't have any mutation; therefore adherence could be major issue in these groups of individuals. We propose continued viral load monitoring for better management of infected PLHIV.

Project description:ImportanceImmune checkpoint inhibitors have been approved for use as a second-line therapy for hepatocellular carcinoma (HCC) in patients who previously received sorafenib. Pembrolizumab has shown substantial antitumor activity and a favorable toxicity profile as a second-line treatment of HCC. However, considering the high cost of pembrolizumab, there is a need to assess its value by considering both the clinical efficacy and cost.ObjectiveTo evaluate the cost-effectiveness of pembrolizumab vs placebo as second-line therapy in patients with HCC from the US payer perspective.Design, setting, and participantsA Markov model was developed to compare the lifetime cost and efficacy of pembrolizumab as a second-line treatment of HCC with those of placebo using outcome data from the KEYNOTE-240 randomized placebo-controlled trial, which included 413 patients with advanced HCC previously treated with sorafenib and randomized patients to receive pembrolizumab plus best supportive care or placebo plus best supportive care in a 2:1 ratio.Main outcomes and measuresLife-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER) were estimated at a willingness-to-pay threshold of $150 000 per QALY. One-way and probabilistic sensitivity analyses were performed to account for the parameter of uncertainty. A cost-threshold analysis was also performed. The study was conducted from January 31 to July 29, 2020.ResultsThe base-case model found that treatment with pembrolizumab was associated with increased overall cost by $47 057 and improved effectiveness by 0.138 QALYs compared with placebo, leading to an ICER of $340 409 per QALY. The model was most sensitive to the hazard ratio of overall survival (range, 0.61-1.00), health utility of placebo (range, 0.59-0.93), price of pembrolizumab (range, $5531-$8297), and price of postprogression therapies (range, $5596-$7944 for pembrolizumab and $4770-$7156 for placebo). The ICER of pembrolizumab was larger than $150 000 per QALY in most of the sensitivity and subgroup analyses. The price of pembrolizumab needed to be reduced by 57.7% to $2925 per cycle to achieve cost-effectiveness.Conclusions and relevanceThe findings of this cost-effectiveness analysis suggest that, at its current price, pembrolizumab is not a cost-effective second-line therapy for HCC in the US, with a willingness-to-pay threshold of $150 000 per QALY.

Dataset Information

Cost-Effectiveness of Three Alternative Boosted Protease Inhibitor-Based Second-Line Regimens in HIV-Infected Patients in West and Central Africa.

Publications

Cost-Effectiveness of Three Alternative Boosted Protease Inhibitor-Based Second-Line Regimens in HIV-Infected Patients in West and Central Africa.

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