Cost effectiveness of single-dose nevirapine regimen for mothers and babies to decrease vertical HIV-1 transmission in sub-Saharan Africa

Cassia abbreviata is widely used in Sub-Saharan Africa for treating many diseases, including HIV-1 infection. We have recently described the chemical structures of 28 compounds isolated from an alcoholic crude extract of barks and roots ofC. abbreviata, and showed that six bioactive compounds inhibit HIV-1 infection. In the present study, we demonstrate that the six compounds block HIV-1 entry into cells: oleanolic acid, palmitic acid, taxifolin, piceatannol, guibourtinidol-(4α®8)-epiafzelechin, and a novel compound named as cassiabrevone. We report, for the first time, that guibourtinidol-(4α®8)-epiafzelechin and cassiabrevone inhibit HIV-1 entry (IC50 of 42.47 µM and 30.96 µM, respectively), as well as that piceatannol interacts with cellular membranes. Piceatannol inhibits HIV-1 infection in a dual-chamber assay mimicking the female genital tract, as well as HSV infection, emphasizing its potential as a microbicide. Structure-activity relationships (SAR) showed that pharmacophoric groups of piceatannol are strictly required to inhibit HIV-1 entry. By a ligand-based in silico study, we speculated that piceatannol and norartocarpetin may have a very similar mechanism of action and efficacy because of the highly comparable pharmacophoric and 3D space, while guibourtinidol-(4α®8)-epiafzelechin and cassiabrevone may display a different mechanism. We finally show that cassiabrevone plays a major role of the crude extract of CA by blocking the binding activity of HIV-1 gp120 and CD4.

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Addressing Pediatric HIV Pretreatment Drug Resistance and Virologic Failure in Sub-Saharan Africa: A Cost-Effectiveness Analysis of Diagnostic-Based Strategies in Children ≥3 Years Old

Diagnostics ◽

10.3390/diagnostics11030567 ◽

2021 ◽

Vol 11 (3) ◽

pp. 567

Author(s):

Mutita Siriruchatanon ◽

Shan Liu ◽

James G. Carlucci ◽

Eva A. Enns ◽

Horacio A. Duarte

Keyword(s):

Drug Resistance ◽

Cost Effectiveness ◽

Virologic Failure ◽

Pediatric Hiv ◽

Sub Saharan Africa ◽

Financial Investment ◽

Switching Strategy ◽

Wide Range ◽

Sub Saharan ◽

Living With Hiv

Improvement of antiretroviral therapy (ART) regimen switching practices and implementation of pretreatment drug resistance (PDR) testing are two potential approaches to improve health outcomes for children living with HIV. We developed a microsimulation model of disease progression and treatment focused on children with perinatally acquired HIV in sub-Saharan Africa who initiate ART at 3 years of age. We evaluated the cost-effectiveness of diagnostic-based strategies (improved switching and PDR testing), over a 10-year time horizon, in settings without and with pediatric dolutegravir (DTG) availability as first-line ART. The improved switching strategy increases the probability of switching to second-line ART when virologic failure is diagnosed through viral load testing. The PDR testing strategy involves a one-time PDR test prior to ART initiation to guide choice of initial regimen. When DTG is not available, PDR testing is dominated by the improved switching strategy, which has an incremental cost-effectiveness ratio (ICER) of USD 579/life-year gained (LY), relative to the status quo. If DTG is available, improved switching has a similar ICER (USD 591/LY) relative to the DTGstatus quo. Even when substantial financial investment is needed to achieve improved regimen switching practices, the improved switching strategy still has the potential to be cost-effective in a wide range of sub-Saharan African countries. Our analysis highlights the importance of strengthening existing laboratory monitoring systems to improve the health of children living with HIV.

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Are low and middle-income countries prioritising high-value healthcare interventions?

BMJ Global Health ◽

10.1136/bmjgh-2019-001850 ◽

2020 ◽

Vol 5 (2) ◽

pp. e001850

Author(s):

Ashley A Leech ◽

David D Kim ◽

Joshua T Cohen ◽

Peter J Neumann

Keyword(s):

Cost Effectiveness ◽

Cost Saving ◽

National Health ◽

Sub Saharan Africa ◽

Health Plans ◽

Middle Income ◽

Middle Income Countries ◽

Health Priority ◽

Sub Saharan ◽

Low And Middle Income

IntroductionSince resources are finite, investing in services that produce the highest health gain ‘return on investment’ is critical. We assessed the extent to which low and middle-income countries (LMIC) have included cost-saving interventions in their national strategic health plans.MethodsWe used the Tufts Medical Center Global Health Cost-Effectiveness Analysis Registry, an open-source database of English-language cost-per-disability-adjusted life year (DALY) studies, to identify analyses published in the last 10 years (2008–2017) of cost-saving health interventions in LMICs. To assess whether countries prioritised cost-saving interventions within their latest national health strategic plans, we identified 10 countries, all in sub-Saharan Africa, with the highest measures on the global burden of disease scale and reviewed their national health priority plans.ResultsWe identified 392 studies (63%) targeting LMICs that reported 3315 cost-per-DALY ratios, of which 207 ratios (6%) represented interventions reported to be cost saving. Over half (53%) of these targeted sub-Saharan Africa. For the 10 countries we investigated in sub-Saharan Africa, 58% (79/137) of cost-saving interventions correspond with priorities identified in country plans. Alignment ranged from 95% (21/22 prioritised cost-saving ratios) in South Africa to 17% (2/12 prioritised cost-saving ratios) in Cameroon. Human papillomavirus vaccination was a noted priority in 70% (7/10) of national health prioritisation plans, while 40% (4/10) of countries explicitly included prenatal serological screening for syphilis. HIV prevention and treatment were stated priorities in most country health plans, whereas 40% (2/5) of countries principally outlined efforts for lymphatic filariasis. From our sample of 45 unique interventions, 36% of interventions (16/45) included costs associated directly with the implementation of the intervention.ConclusionOur findings indicate substantial variation across country and disease area in incorporating economic evidence into national health priority plans in a sample of sub-Saharan African countries. To make health economic data more salient, the authors of cost-effectiveness analyses must do more to reflect implementation costs and other factors that could limit healthcare delivery.

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