Assessment of swallowability and acceptability of scored darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) tablets in HIV-1-infected children aged ≥6 to <12 years, using matching placebo tablets: A randomized study.

BACKGROUND: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) was developed as a once-daily, complete antiretroviral (ARV) regimen therapy to address the need for simplified protease inhibitor-based ARV regimens. This study assessed the swallowability and acceptability for long-term use of scored placebo tablets matching the D/C/F/TAF FDC tablets in children living with HIV-1. METHODS: This study (NCT04006704) was a Phase 1, open-label, randomized, single-dose, 2-period, 2-sequence crossover study in children living with HIV-1, aged ≥6 to <12 years and weighing ≥25 to <40 kg, on a stable ARV regimen for ≥3 months. Participants were asked to swallow whole (size, 21 × 11 × 7 mm) and split matching placebo D/C/F/TAF tablets. Swallowability of the matching placebo D/C/F/TAF tablets (primary endpoint) was assessed by observers. Acceptability of taking matching placebo D/C/F/TAF tablets and current ARVs was evaluated by participants using a 3-point questionnaire. Participants rated the acceptability for long-term daily use of the placebo D/C/F/TAF tablets, and observers assessed how easily caregivers could split a scored tablet by hand, using 3-point questionnaires. RESULTS: Among the 24 participants who enrolled and completed the study, 95.8% (23/24) were able to swallow the whole and split matching placebo D/C/F/TAF tablets after 1 or 2 attempts. Most participants (>70%) rated the acceptability of tablets for long-term daily use as acceptable or good to take. Breaking the tablets was considered easy or OK by 79.2% (19/24) of caregivers. CONCLUSION: Scored D/C/F/TAF FDC tablets are swallowable - with whole favoured over split - and considered at least acceptable for long-term daily intake in children living with HIV-1 aged ≥6 to <12 years. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04006704.

Cost-effectiveness of switching from tenofovir disoproxil fumarate to tenofovir alafenamide versus entecavir for chronic hepatitis B patients in Greece.

Aim: This study assessed the clinical impact and cost-effectiveness of switching from tenofovir disoproxil fumarate (TDF) to either tenofovir alafenamide (TAF) or entecavir (ETV) in a Greek chronic hepatitis B (CHB) population. Patients & methods: A Markov model from the perspective of a third-party payer in Greece quantified the health and economic benefits of switching from TDF to either TAF or ETV over a lifetime horizon. Results: Over a lifetime, patients who switch from TDF to TAF versus patients who switch from TDF to ETV had an overall lower incidence of compensated cirrhosis (0.4% lower), decompensated cirrhosis (0.04% lower) and hepatocellular carcinoma (0.25% lower). Chronic kidney disease and end-stage renal disease were also lower in patients who switch to TAF; major osteoporotic fractures were similar for both groups. While total costs were higher for switching from TDF to TAF versus TDF to ETV due to the higher cost of TAF, switching from TDF to TAF versus ETV was cost effective with an incremental cost-effectiveness ratio of €17,113 per quality-adjusted life year. Conclusion: Switching from TDF to TAF in patients living with CHB is a cost effective strategy to reduce adverse liver disease outcomes, while improving bone- and renal-related safety outcomes.

Long-term health and economic benefits of switching to tenofovir alafenamide versus continuing on entecavir in chronic hepatitis B patients with low-level viremia in Saudi Arabia.

BACKGROUND: Despite the success of current treatments, many chronic hepatitis B (CHB) patients still live with low-level viremia [LLV] resulting in liver disease progression. This study evaluated the long-term health and economic impact of switching to tenofovir alafenamide (TAF) from entecavir (ETV) in Saudi Arabia (SA) in chronic hepatitis B (CHB) LLV patients. METHODS: A hybrid decision tree Markov state-transition model was developed to simulate a cohort of patients with CHB LLV treated with ETV and switched to TAF over a lifetime horizon in SA. While on treatment, patients either achieved complete virologic response (CVR) or maintained LLV. CVR patients experienced slower progression to advanced liver disease stages as compared to LLV patients. Demographic data, transition probabilities, treatment efficacy, health state costs, and utilities were sourced from published literature. Treatment costs were sourced from publicly available databases. RESULTS: Base case analysis found that over a lifetime horizon, switching to TAF versus remaining on ETV increased the proportion of patients achieving CVR (76% versus 14%, respectively). Switching to TAF versus remaining on ETV resulted in a reduction in cases of compensated cirrhosis (-52%), decompensated cirrhosis (-5%), hepatocellular carcinoma (-22%), liver transplants (-12%), and a 37% reduction in liver-related deaths. Switching to TAF was cost-effective with an incremental cost-effectiveness ratio of $57,222, assuming a willingness-to-pay threshold of three times gross national income per capita [$65,790/QALY]. CONCLUSIONS: This model found that switching to TAF versus remaining on ETV in SA CHB LLV patients substantially reduced long-term CHB-related morbidity and mortality and was a cost-effective treatment strategy.

Global HIV Incidence Analysis and Implications for Affordability Using Long-Acting Cabotegravir Versus Continuous and Event-Driven Oral Preexposure Prophylaxis.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 083/084 trials showed up to 88% increased efficacy of long-acting cabotegravir (CAB-LA) versus continuous oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). However, CAB-LA's high price limits the number of people who can be treated within fixed prevention budgets. Global human immunodeficiency virus (HIV) prevention budgets are highly limited, with TDF/FTC widely available as a low-cost generic. In randomized clinical trials, event-driven TDF/FTC has shown similar preventive efficacy to continuous TDF/FTC. METHODS: A systematic review of global HIV incidence studies was conducted. Weighted incidence was calculated in each at-risk population. HIV infection rates were evaluated for 5 prevention strategies, with additional HIV testing, education, and service access costs assumed for each ($18 per person per year). Assumed efficacies were 90% (continuous CAB-LA), 60% (continuous TDF/FTC), and 60% (event-driven TDF/FTC). Using weighted incidence and an assumed 100 000 target population, annual HIV infection rates by population were calculated for each prevention strategy. RESULTS: Ninety-eight studies in 5 230 189 individuals were included. Incidence per 100 person-years ranged from 0.03 (blood donors) to 3.82 (people who inject drugs). Using the number needed to treat to benefit for each strategy, a mean incidence of 2.6 per 100 person-years in at-risk populations, and a 100 000 target population, current-price continuous CAB-LA cost $949 487 per HIV infection successfully prevented, followed by target-price CAB-LA ($11 453), continuous TDF/FTC ($4231), and event-driven TDF/FTC ($1923). CONCLUSIONS: High prices of CAB-LA limit numbers treatable within fixed budgets. Low-cost event-driven TDF/FTC consistently prevents the most HIV infections within fixed budgets.

Geographic Variation in Qualified Health Plan Coverage and Prior Authorization Requirements for HIV Preexposure Prophylaxis.

Importance: HIV preexposure prophylaxis (PrEP) is a key component of the Ending the HIV Epidemic (EHE) Initiative to curb new HIV diagnoses. In October 2019, emtricitabine/tenofovir alafenamide was added as an approved formulation for PrEP in addition to emtricitabine/tenofovir disoproxil fumarate; despite availability of another formulation with a similar prevention indication, variations in coverage may limit access. Objective: To assess qualified health plan (QHP) coverage, prior authorization (PA) requirements, and specialty tiering for emtricitabine/tenofovir disoproxil fumarate and emtricitabine/tenofovir alafenamide following emtricitabine/tenofovir alafenamide approval as a PrEP treatment. Design, Setting, and Participants: This cross-sectional study analyzed QHPs in the US that were compliant with the Patient Protection and Affordable Care Act from 2018 to 2020. QHPs were categorized by region and EHE priority jurisdictions. Data analysis occurred from March 2022 to March 2023. Exposures: Enrollment in a qualified health plan certified by the Patient Protection and Affordable Care Act. Main Outcome and Measures: Annual variation in QHP coverage and PA requirement for emtricitabine/tenofovir disoproxil fumarate and/or emtricitabine/tenofovir alafenamide. Descriptive statistics were reported for all outcomes. A secondary outcome was whether the PrEP formulation was determined by the QHP to be placed on a specialty drug tier. Results: A total of 58 087 QHPs (19 533 for 2018; 17 007 for 2019; and 21 547 for 2020) were analyzed. QHPs covered emtricitabine/tenofovir disoproxil fumarate (19 165 QHPs [98.1%] in 2018; 16 970 QHPs [99.8%] in 2019; 20 045 QHPs [94.8%] in 2020) at a higher rate than emtricitabine/tenofovir alafenamide (17 391 QHPs [91.9%] in 2018; 15 757 QHPs [92.7%] in 2019; 18 836 QHPs [87.4%] in 2020). QHPs in the South required exclusive PA (ie, PA for 1 of the formulations even if the QHP covered both) for emtricitabine/tenofovir disoproxil fumarate and emtricitabine/tenofovir alafenamide at the highest rates in all 3 years. In the South, the rate of PA for emtricitabine/tenofovir disoproxil fumarate increased from 806 of 8023 QHPs (10.0%) in 2018 to 3466 of 7401 QHPs (46.8%) in 2020. QHPs with exclusive PA requirement for emtricitabine/tenofovir disoproxil fumarate were higher in EHE jurisdictions than non-EHE jurisdictions (difference: 2018, 0.9 percentage points; 2019, 3.5 percentage points; 2020, 29.1 percentage points). QHPs were more likely to place emtricitabine/tenofovir disoproxil fumarate on a specialty tier compared with emtricitabine/tenofovir alafenamide (difference: 2018, 1.8 percentage points; 2019, 3.7 percentage points; 2020, 4.1 percentage points). Conclusions and Relevance: In this cross-sectional study, despite similar indications for biomedical prevention, QHPs were more likely to cover emtricitabine/tenofovir disoproxil fumarate than emtricitabine/tenofovir alafenamide, and QHPs were also more likely to subject emtricitabine/tenofovir disoproxil fumarate to PA or place it on a specialty tier despite the broader clinical indication. QHP PA requirements of emtricitabine/tenofovir disoproxil fumarate following emtricitabine/tenofovir alafenamide approval does not reflect clinical guidelines. The requirements could reflect differences in clinical indication, manufacturer discounts, or anticipation of a changing regulations and emerging generics. High rates of exclusive PA for emtricitabine/tenofovir disoproxil fumarate in areas where rates of HIV diagnoses are highest and PrEP is most needed (eg, the South and EHE priority jurisdictions) is concerning; policy solutions to address the growing PrEP health equity crisis could include regulator actions and a national PrEP program.

Potential cost-effectiveness of community availability of tenofovir, lamivudine, and dolutegravir for HIV prevention and treatment in east, central, southern, and west Africa: a modelling analysis.

BACKGROUND: Post-exposure prophylaxis (PEP) offers protection from HIV after condomless sex, but is not widely available in a timely manner in east, central, southern, and west Africa. To inform the potential pilot implementation of such an approach, we modelled the effect and cost-effectiveness of making PEP consisting of tenofovir, lamivudine, and dolutegravir (TLD) freely and locally available in communities without prescription, with the aim of enabling PEP use within 24 h of condomless sex. Free community availability of TLD (referred to as community TLD) might also result in some use of TLD as pre-exposure prophylaxis (PrEP) and as antiretroviral therapy for people living with HIV. METHODS: Using an existing individual-based model (HIV Synthesis), we explicitly modelled the potential positive and negative effects of community TLD. Through the sampling of parameter values we created 1000 setting-scenarios, reflecting the uncertainty in assumptions and a range of settings similar to those seen in east, central, southern, and west Africa (with a median HIV prevalence of 14·8% in women and 8·1% in men). For each setting scenario, we considered the effects of community TLD. TLD PEP was assumed to have at least 90% efficacy in preventing HIV infection after condomless sex with a person living with HIV. FINDINGS: The modelled effects of community TLD availability based on an assumed high uptake of TLD resulted in a mean reduction in incidence of 31% (90% range over setting scenarios, 6% increase to 57% decrease) over 20 years, with an HIV incidence reduction over 50 years in 91% of the 1000 setting scenarios, deaths averted in 55% of scenarios, reduction in costs in 92% of scenarios, and disability-adjusted life-years averted in 64% of scenarios with community TLD. Community TLD was cost-effective in 90% of setting scenarios and cost-saving (with disability-adjusted life-years averted) in 58% of scenarios. When only examining setting scenarios in which there was lower uptake of community TLD, community TLD is cost-effective in 92% of setting scenarios. INTERPRETATION: The introduction of community TLD, enabling greater PEP access, is a promising approach to consider further in pilot implementation projects. FUNDING: Bill & Melinda Gates Foundation to the HIV Modelling Consortium.

Cost-effectiveness of tenofovir prophylaxis during pregnancy for the elimination of mother-to-child transmission of the hepatitis B virus: real-world analysis from Thailand.

OBJECTIVE: Despite implementing hepatitis B immunoglobulin (HBIG) and vaccination, data suggest it would not be sufficient to reach the elimination targets. Tenofovir disoproxil fumarate (TDF) has been added to the Thai national standards of care for prevention of transmission of the hepatitis B virus during birth. To optimise national strategies in Thailand, we assessed TDF's effectiveness for prevention of mother-to-child transmission and conducted cost-effectiveness analyses of different TDF-based strategies. RESEARCH DESIGN AND METHODS: We retrospectively reviewed medical records of mother and infant pairs whose mothers were positive for hepatitis B e-antigen (HBeAg) and received TDF to prevent maternal transmission of viral hepatitis B during 2018-2020. Based on the available data on transmission rate, we also applied a decision tree to estimate the cost-effectiveness of different TDF-based strategies to eligible mothers. These included: (1) HBIG for all hepatitis B virus (HBV) exposed infants; (2) HBIG for only infants of HBeAg-positive mothers ('HBIG for e-positive') and (3) without HBIG to infants ('HBIG-free'). The incremental cost-effectiveness ratio between the different strategies and baseline intervention without TDF was calculated. The one-way sensitivity analysis was used to adjust prevalence of HBeAg-positive mothers, cost of HBIG, cost of TDF and transmission rate. RESULTS: Of 223 infants enrolled, 212 (95.0%) received HBIG, while 11 (5.0%) did not. None of the infants had chronic HBV infection. The most cost-saving intervention was 'HBIG-free' followed by 'HBIG for e-positive'. The one-way sensitivity demonstrated that the results were reasonably robust to changes. The cost-saving was greater with a higher hepatitis B virus surface antigen (HBsAg) prevalence. The HBIG-free strategy remained best at 0%-1.4% transmission rates, meeting the additional target for eliminations. CONCLUSION: The study is the first cost-effectiveness analyses to provide evidence supporting an HBIG-free strategy in an antiviral era. This approach should be considered to prevent mother-to-child transmission in resource-constrained settings, particularly in countries with a high HBsAg prevalence.

Utilization of Chemometric-Aided UV Spectrophotometric Methods for Concurrent Assessment of Emtricitabine, Tenofovir Disoproxil Fumarate, Elvitegravir, and Cobicistat in Tablet Formulation.

BACKGROUND: Emtricitabine (ETC), tenofovir disoproxil fumarate (TNF), elvitegravir (EVG), and cobicistat (CBS) are antiviral drugs used to treat human immunodeficiency virus (HIV) infections. OBJECTIVE: To develop chemometric-aided UV spectrophotometric methods for concurrent estimation of the aforementioned drugs used to treat HIV. This method can be used to reduce modification of the calibration model by assessing the absorbance at various points in the zero-order spectra within the selected wavelength range. Additionally, it eliminates interfering signals and provides sufficient resolution in multi-component systems. METHODS: Two chemometric-assisted UV spectrophotometric methods, namely, partial least-squares (PLS) and principal component regression (PCR) models, were established for the concurrent assessment of EVG, CBS, TNF, and ETC in tablet formulations. The proposed methods were applied to decrease complexity of overlapped spectra and to achieve maximum sensitivity and the lowest error. These approaches were performed in accordance with International Council on Harmonization (ICH) criteria and compared to the reported HPLC method. RESULTS: The proposed methods were used to assess EVG, CBS, TNF, and ETC in the ranges of 5-30, 5-30 , 5-50, and 5-50 µg/mL, respectively, with an excellent correlation coefficient (r2 ≥ 0.998). The accuracy and precision results were found to be within the acceptable limits. No statistical difference was observed between the proposed and reported studies. CONCLUSION: The chemometric-aided UV spectrophotometric approaches could be considered as alternatives to chromatographic procedures in the pharmaceutical industry for routine analysis and testing of readily accessible commercial formulations. HIGHLIGHTS: Novel chemometric-assisted UV spectrophotometric techniques were developed for assessment of multicomponent antiviral combinations in single-tablet formulations. The proposed methods were performed without using harmful solvents, tedious preparation, or expensive instruments. The proposed methods were compared statistically with a reported HPLC method. Assessment of EVG, CBS, TNF, and ETC was performed without interference from excipients in their multicomponent formulations.

Federal Funding For Discovery And Development Of Costly HIV Drugs Was Far More Than Previously Estimated.

In July 2012, tenofovir disoproxil fumarate-emtricitabine (TDF-FTC, brand name Truvada) was approved by the Food and Drug Administration (FDA) to prevent HIV infection. To estimate the extent of the US government's direct financial contribution to the discovery and development of Truvada, we identified National Institutes of Health awards using FDA documents, peer-reviewed literature, patent records, court filings, and other publicly available materials. We classified seventy-three federal government awards to eleven researchers as being directly linked to the development and clinical testing of Truvada for prevention therapy, through which the US government spent an estimated $143 million. The substantial public funding raises questions about the high price charged by the drug's manufacturer, which reduced its affordability and limited its accessibility as HIV preventive therapy.

Contingency Management for Integrated Harm Reduction Among Men Who Have Sex with Men Who Use Methamphetamine in Los Angeles: A Pilot Assessment.

Methamphetamine (MA) use is associated with HIV transmission among men who have sex with men (MSM) and lapses in medication adherence. Contingency Management (CM) is effective in reducing MA use, but studies of CM to support adherence to HIV prevention or treatment are limited. We conducted a pilot trial of a CM intervention to reduce MA use and improve PrEP/ART adherence among MSM prescribed a tenofovir (TFV)-based regimen for HIV prevention or treatment. Participants were randomly assigned to receive escalating incentives for either MA abstinence or TFV adherence (based on point-of-care urine testing), and to a monitoring schedule of either 2 or 3 visits/week for 4 weeks. 19 MSM were randomized to either CM for MA use or CM for PrEP/ART adherence (median age: 38; IQR: 28-46) and 15 were living with HIV. Participants attended 95.7% (67/70) of scheduled visits in the 2x/week arm and 74.8% (74/99) in the 3x/week arm. TFV adherence was higher among participants in the TFV adherence arm with 93.5% (n = 72/77) of urine samples positive for TFV, compared to 76.6% (n = 49/64) in the MA abstinence arm (p = 0.007). Participants in the MA abstinence arm had more urine samples negative for MA metabolites (20.3%, n = 13/64) than those receiving CM for TFV adherence (6.5%, n = 5/77; p = 0.021). A CM model for MA abstinence and PrEP/ART adherence using twice-weekly visits and urine testing for MA and TFV for MSM who use MA is feasible and potentially effective as an integrated harm reduction strategy.

Relative cost-effectiveness of long-acting injectable cabotegravir versus oral pre-exposure prophylaxis in South Africa based on the HPTN 083 and HPTN 084 trials: a modelled economic evaluation and threshold analysis.

BACKGROUND: Long-acting injectable cabotegravir, a drug taken every 2 months, has been shown to be more effective at preventing HIV infection than daily oral tenofovir disoproxil fumarate and emtricitabine, but its cost-effectiveness in a high-prevalence setting is not known. We aimed to estimate the incremental cost-effectiveness of long-acting injectable cabotegravir compared with tenofovir disoproxil fumarate and emtricitabine in South Africa, using methods standard to government planning, and to determine the threshold price at which long-acting injectable cabotegravir is as cost-effective as tenofovir disoproxil fumarate and emtricitabine. METHODS: In this modelled economic evaluation and threshold analysis, we updated a deterministic model of the South African HIV epidemic with data from the HPTN 083 and HPTN 084 trials to evaluate the effect of tenofovir disoproxil fumarate and emtricitabine and long-acting injectable cabotegravir provision to heterosexual adolescents and young women and men aged 15-24 years, female sex workers, and men who have sex with men. We estimated the average intervention cost, in 2021 US$, using ingredients-based costing, and modelled the cost-effectiveness of two coverage scenarios (medium or high, assuming higher uptake of long-acting injectable cabotegravir than tenofovir disoproxil fumarate and emtricitabine throughout) and, for long-acting injectable cabotegravir, two duration subscenarios (minimum: same pre-exposure prophylaxis duration as for tenofovir disoproxil fumarate and emtricitabine; maximum: longer duration than tenofovir disoproxil fumarate and emtricitabine) over 2022-41. FINDINGS: Across long-acting injectable cabotegravir scenarios, 15-28% more new HIV infections were averted compared with the baseline scenario (current tenofovir disoproxil fumarate and emtricitabine roll-out). In scenarios with increased coverage with oral tenofovir disoproxil fumarate and emtricitabine, 4-8% more new HIV infections were averted compared with the baseline scenario. If long-acting injectable cabotegravir drug costs were equal to those of tenofovir disoproxil fumarate and emtricitabine for the same 2-month period, the incremental cost of long-acting injectable cabotegravir to the HIV programme was higher than that of tenofovir disoproxil fumarate and emtricitabine (5-10% vs 2-4%) due to higher assumed uptake of long-acting injectable cabotegravir. The cost per infection averted was $6053-6610 (tenofovir disoproxil fumarate and emtricitabine) and $4471-6785 (long-acting injectable cabotegravir). The cost per long-acting cabotegravir injection needed to be less than twice that of a 2-month supply of tenofovir disoproxil fumarate and emtricitabine to remain as cost-effective, with threshold prices ranging between $9·03 per injection (high coverage; maximum duration) and $14·47 per injection (medium coverage; minimum duration). INTERPRETATION: Long-acting injectable cabotegravir could potentially substantially change HIV prevention. However, for its implementation to be financially feasible across low-income and middle-income countries with high HIV incidence, long-acting injectable cabotegravir must be reasonably priced. FUNDING: United States Agency for International Development, The Bill & Melinda Gates Foundation.

Estimated changes in price discounts for tenofovir-inclusive HIV treatments following introduction of tenofovir alafenamide.

We estimated list and net prices for tenofovir disoproxil fumarate (TDF) products Truvada, Complera, and Stribild, and their tenofovir alafenamide (TAF) versions Descovy, Odefsey, and Genvoya. Gilead offered discounts for Descovy that resulted into lower net prices compared to Truvada. This strategy encouraged patients switching from Truvada to Descovy before the availability of generic Truvada. Conversely, Gilead offered lower discounts for Odefsey and Genvoya, which resulted into higher net prices compared to Complera and Stribild.

Assessment of Adherence to Clinical Guidelines in Patients with Chronic Hepatitis B.

Background and aims: Adherence to guidelines is associated with improved long-term outcomes in patients with chronic hepatitis B (CHB). We aimed to study the degree of adherence and determinants of non-adherence to management guidelines in a low endemic country. Methods: We reviewed the medical records of all CHB patients who visited our outpatient clinic in 2020. Adherence to guidelines was assessed based on predefined criteria based on the EASL guidance, and included the initiation of antiviral therapy when indicated, the optimal choice of antiviral therapy based on comorbidities, an assessment of HAV/HCV/HDV/HIV serostatus, renal function monitoring and enrolment in a HCC surveillance program if indicated. The adherence rates were compared across types of outpatient clinic (dedicated viral hepatitis clinic versus general hepatology clinic). Results: We enrolled 482 patients. Among the 276 patients with an indication for antiviral therapy, 268 (97.1%) received treatment. Among the patients with renal and/or bone disease, 26/29 (89.7%) received the optimal choice of antiviral agent. The assessment of HAV/HCV/HDV/HIV serostatus was performed in 86.1/91.7/94.4/78.4%. Among the 91 patients treated with tenofovir disoproxil, 57 (62.6%) underwent monitoring of renal function. Of the 241 patients with an indication for HCC surveillance, 212 (88.3%) were enrolled in a surveillance program. Clinics dedicated to viral hepatitis had superior adherence rates compared to general hepatology clinics (complete adherence rates 63.6% versus 37.2%, p < 0.001). Conclusions: Follow-up at a dedicated viral hepatitis clinic was associated with superior adherence to management guidelines.

Estimating the budget impact of adopting tenofovir/emtricitabine for pre-exposure prophylaxis of HIV in the public health sector in Namibia (2021 - 2023).

BACKGROUND: Although Namibia started implementing pre-exposure prophylaxis (PrEP) of Human Immunodeficiency Virus (HIV) in 2016, no study to determine its budget impact has been conducted. This study, therefore, aimed to estimate the budget impact of adopting tenofovir/emtricitabine for PrEP of HIV for all eligible people in the public health sector in Namibia from 2021 to 2023. METHODS: A country-specific model was developed for this budget impact analysis (BIA). PrEP has targeted all eligible people in Namibia who receive health services from the public sector. It was assumed that the adherence rate was 75% and PrEP effectiveness 60% in this study. Costs used in this study were taken from a study that included Namibian costs. RESULTS: The BIA suggests that adopting PrEP may be cost saving as US$104 823, US$143 620, and US$182 452 of additional HIV care costs will potentially be saved in 2021, 2022, and 2023, respectively. Cost savings rely on high adherence rates, high PrEP effectiveness rates, low PrEP costs, and a small number of people living with HIV (PLHIV). CONCLUSION: Further economic analysis could aid decision-making in Namibia, both to stress test assumptions in the BIA and conduct cost-effectiveness analysis to estimate the value for money of PrEP.

Economic evaluation of doravirine/tenofovir disoproxil fumarate/lamivudine for HIV-1-infected adults in Russia: a cost-minimization and budget impact analysis.

BACKGROUND: In Russia, before 2022, the list of vital and essential drugs for HIV-infected patients previously untreated with antiretroviral drugs included the fixed-dose combination rilpivirine/tenofovir disoproxil fumarate/emtricitabine (RPV/TDF/FTC) but not doravirine/tenofovir disoproxil fumarate/lamivudine (DOR/TDF/3TC). METHODS: An indirect comparison of the efficacy of DOR/TDF/3TC and RPV/TDF/FTC defined by virologic suppression (HIV-1 RNA of <50 copies/mL at week 48) was made. The per-patient drug costs over 1 year were compared in a cost-minimization analysis. A budget impact analysis considered the costs to the healthcare system of including DOR/TDF/3TC as a treatment option for eligible patients in Russia over a 3-year time horizon. RESULTS: The indirect treatment comparison of DOR/TDF/3TC and RPV/TDF/FTC in treatment-naïve patients with baseline HIV-1 RNA 100,000 copies/ml or less showed no statistically significant difference (RR 0.914, 95% CI 0.833-1.003). In the cost-minimization analysis, the per-patient cost of one year of treatment with RPV/TDF/FTC and DOR/TDF/3TC was, respectively, ₽320,975 and ₽151,192, for a saving of ₽169,783. In the budget impact analysis, the adoption of DOR/TDF/3TC into clinical practice is expected to reduce drug costs by ₽333 million (23.8%) in year 3. CONCLUSIONS: Fixed-dose combination DOR/TDF/3TC is equally effective and cost-saving compared to RPV/TDF/FTC from Russian vital and essential drugs list perspective.

Stepped care to optimize pre-exposure prophylaxis (PrEP) effectiveness in pregnant and postpartum women (SCOPE-PP) in South Africa: a randomized control trial.

BACKGROUND: HIV incidence among pregnant and postpartum women remains high in South Africa. Pre-exposure prophylaxis (PrEP) use remains suboptimal in this population, particularly during the postpartum period when women's engagement with routine clinic visits outside PrEP decreases. Key barriers to sustained PrEP use include the need for ongoing contact with the health facility and suboptimal counseling around effective PrEP use. METHODS: Stepped Care to Optimize PrEP Effectiveness in Pregnant and Postpartum women (SCOPE-PP), is a two-stepped unblinded, individually randomized controlled trial (RCT) that aims to optimize peripartum and postpartum PrEP use by providing a stepped package of evidence-based interventions. We will enroll 650 pregnant women (> 25 weeks pregnant) who access PrEP at a busy antenatal clinic in Cape Town at the time of recruitment and follow them for 15 months. We will enroll and individually randomize pregnant women > 16 years who are not living with HIV who are either on PrEP or interested in starting PrEP during pregnancy. In step 1, we will evaluate the impact of enhanced adherence counselling and biofeedback (using urine tenofovir tests for biofeedback) and rapid PrEP collection (to reduce time required) on PrEP use in early peripartum compared to standard of care (SOC) (n = 325 per arm). The primary outcome is PrEP persistence per urine tenofovir levels and dried blood spots of tenofovir diphosphate (TFV-DP) after 6-months. The second step will enroll and individually randomize participants from Step 1 who discontinue taking PrEP or have poor persistence in Step 1 but want to continue PrEP. Step 2 will test the impact of enhanced counseling and biofeedback plus rapid PrEP collection compared to community PrEP delivery with HIV self-testing on PrEP use (n = up to 325 postpartum women). The primary outcome is PrEP continuation and persistence 6-months following second randomization (~ 9-months postpartum). Finally, we will estimate the cost effectiveness of SCOPE-PP vs. SOC per primary outcomes and disability-adjusted life-years (DALYs) averted in both Step 1 and 2 using micro-costing with trial- and model-based economic evaluation. DISCUSSION: This study will provide novel insights into optimal strategies for delivering PrEP to peripartum and postpartum women in this high-incidence setting. TRIAL REGISTRATION: NCT05322629 : Date of registration: April 12, 2022.