Cost-effectiveness of broadly neutralizing antibodies for infant HIV prophylaxis in settings with high HIV burdens: a simulation modeling study.

Introduction: Approximately 130 000 infants acquire HIV annually despite global maternal antiretroviral therapy scale-up. We evaluated the potential clinical impact and cost-effectiveness of offering long-acting, anti-HIV broadly neutralizing antibody (bNAb) prophylaxis to infants in three distinct settings. Methods: We simulated infants in Côte d'Ivoire, South Africa, and Zimbabwe using the Cost-Effectiveness of Preventing AIDS Complications-Pediatric (CEPAC-P) model. We modeled strategies offering a three-bNAb combination in addition to WHO-recommended standard-of-care oral prophylaxis to infants: a) with known, WHO-defined high-risk HIV exposure at birth (HR-HIVE); b) with known HIV exposure at birth (HIVE); or c) with or without known HIV exposure (ALL). Modeled infants received 1-dose, 2-doses, or Extended (every 3 months through 18 months) bNAb dosing. Base case model inputs included 70% bNAb efficacy (sensitivity analysis range: 10-100%), 3-month efficacy duration/dosing interval (1-6 months), and $20/dose cost ($5-$100/dose). Outcomes included pediatric HIV infections, life expectancy, lifetime HIV-related costs, and incremental cost-effectiveness ratios (ICERs, in US$/year-of-life-saved [YLS], assuming a ≤50% GDP per capita cost-effectiveness threshold). Results: The base case model projects that bNAb strategies targeting HIVE and ALL infants would prevent 7-26% and 10-42% additional pediatric HIV infections, respectively, compared to standard-of-care alone, ranging by dosing approach. HIVE-Extended would be cost-effective (cost-saving compared to standard-of-care) in Côte d'Ivoire and Zimbabwe; ALL-Extended would be cost-effective in South Africa (ICER: $882/YLS). BNAb strategies targeting HR-HIVE infants would result in greater lifetime costs and smaller life expectancy gains than HIVE-Extended. Throughout most bNAb efficacies and costs evaluated in sensitivity analyses, targeting HIVE infants would be cost-effective in Côte d'Ivoire and Zimbabwe, and targeting ALL infants would be cost-effective in South Africa. Discussion: Adding long-acting bNAbs to current standard-of-care prophylaxis would be cost-effective, assuming plausible efficacies and costs. The cost-effective target population would vary by setting, largely driven by maternal antenatal HIV prevalence and postpartum incidence.

Accelerating access and scale-up of optimized ART in low-income and middle-income countries: a call for a coordinated end-to-end approach.

PURPOSE OF REVIEW: To discuss how aligning the collective power of scientists, regulators, drug companies, donors, implementers and advocates to achieve a single goal - accelerating access to simpler, safer, more robust and more affordable HIV treatment - can rapidly advance antiretroviral optimization efforts and enable scale-up. RECENT FINDINGS: Harmonization of traditionally sequential processes can address the delays commonly experienced in introducing new products to low-income and middle-income countries, by facilitating an 'end-to-end' approach that mitigates risk and encourages early planning for all aspects of product introduction. SUMMARY: Planning with the 'end-in-mind' can facilitate healthy markets, benefit the application of new technologies, and accelerate the development of improved products in parallel (versus traditionally sequential efforts).

Short-Term Radiographic Complications and Healing Assessment of Single-Session Bilateral Tibial Tuberosity Advancements.

The objective of this study is to report on the short-term radiographic complications and bone healing associated with single-session bilateral tibial tuberosity advancements (TTAs). This retrospective study consists of 74 client-owned dogs with bilateral cranial cruciate ligament rupture that underwent consecutive single-session bilateral TTAs. Radiographs from 74 dogs (148 stifles) were evaluated for evidence of postoperative complications. One hundred forty-three of 148 stifles were scored for radiographic healing using a previously described scoring system. Variables evaluated for a relationship with radiographic complications and healing scores were: breed, age, body weight, sex, and TTA plate type. The overall radiographic complication rate was 17.6% (13/74). Twelve of the 13 radiographic complications were considered to be minor and one was major. Increasing body weight and use of a fork implant were statistically significant factors associated with an increased risk of complication. One hundred forty-three stifle radiographs met the inclusion criteria to be assessed for healing. The mean score was 2.96 out of 4.0. The overall radiographic complication rate and healing scores associated with single-session bilateral TTAs were found to be similar to those described for unilateral TTA.

Prevalence of HIV and hepatitis B virus co-infection in sub-Saharan Africa and the potential impact and program feasibility of hepatitis B surface antigen screening in resource-limited settings.

BACKGROUND: Screening people living with HIV for hepatitis B virus (HBV) co-infection is recommended in resource-rich settings to optimize HIV antiretroviral therapy (ART) and mitigate HBV-related liver disease. This review examines the need, feasibility, and impact of screening for HBV in resource-limited settings (RLS). METHODS: We searched 6 databases to identify peer-reviewed publications between 2007 and 2013 addressing (1) HIV/HBV co-infection frequency in sub-Saharan Africa (SSA); (2) performance of hepatitis B surface antigen (HBsAg) rapid strip assays (RSAs) in RLS; (3) impact of HBV co-infection on morbidity, mortality, or liver disease progression; and/or (4) impact of HBV-suppressive antiretroviral medications as part of ART on at least one of 5 outcomes (mortality, morbidity, HIV transmission, retention in HIV care, or quality of life). We rated the quality of individual articles and summarized the body of evidence and expected impact of each intervention per outcome addressed. RESULTS: Of 3940 identified studies, 85 were included in the review: 55 addressed HIV/HBV co-infection frequency; 6 described HBsAg RSA performance; and 24 addressed the impact of HIV/HBV co-infection and ART. HIV/HBV frequency in sub-Saharan Africa varied from 0% to >28.4%. RSA performance in RLS showed good, although variable, sensitivity and specificity. Quality of studies ranged from strong to weak. Overall quality of evidence for the impact of HIV/HBV co-infection and ART on morbidity and mortality was fair and good to fair, respectively. CONCLUSIONS: Combined, the body of evidence reviewed suggests that HBsAg screening among people living with HIV could have substantial impact on preventing morbidity and mortality among HIV/HBV co-infected individuals in RLS.