Secondary distribution of HIV self-test kits by HIV index and antenatal care clients: implementation and costing results from the STAR Initiative in South Africa.

BACKGROUND: Partner-delivered HIV self-testing kits has previously been highlighted as a safe, acceptable and effective approach to reach men. However, less is known about its real-world implementation in reaching partners of people living with HIV. We evaluated programmatic implementation of partner-delivered self-testing through antenatal care (ANC) attendees and people newly diagnosed with HIV by assessing use, positivity, linkage and cost per kit distributed. METHODS: Between April 2018 and December 2019, antenatal care (ANC) clinic attendees and people or those newly diagnosed with HIV clients across twelve clinics in three cities in South Africa were given HIVST kits (OraQuick Rapid HIV-1/2 Antibody Test, OraSure Technologies) to distribute to their sexual partners. A follow-up telephonic survey was administered to all prior consenting clients who were successfully reached by telephone to assess primary outcomes. Incremental economic costs of the implementation were estimated from the provider's perspective. RESULTS: Fourteen thousand four hundred seventy-three HIVST kits were distributed - 10,319 (71%) to ANC clients for their male partner and 29% to people newly diagnosed with HIV for their partners. Of the 4,235 ANC clients successfully followed-up, 82.1% (3,475) reportedly offered HIVST kits to their male partner with 98.1% (3,409) accepting and 97.6% (3,328) using the kit. Among ANC partners self-testing, 159 (4.8%) reported reactive HIVST results, of which 127 (79.9%) received further testing; 116 (91.3%) were diagnosed with HIV and 114 (98.3%) initiated antiretroviral therapy (ART). Of the 1,649 people newly diagnosed with HIV successfully followed-up; 1,312 (79.6%) reportedly offered HIVST kits to their partners with 95.8% (1,257) of the partners accepting and 95.9% (1,206) reported that their partners used the kit. Among these index partners, 297 (24.6%) reported reactive HIVST results of which 261 (87.9%) received further testing; 260 (99.6%) were diagnosed with HIV and 258 (99.2%) initiated ART. The average cost per HIVST distributed in the three cities was US$7.90, US$11.98, and US$14.81, respectively. CONCLUSIONS: Partner-delivered HIVST in real world implementation was able to affordably reach many male partners of ANC attendees and index partners of people newly diagnosed with HIV in South Africa. Given recent COVID-19 related restrictions, partner-delivered HIVST provides an important strategy to maintain essential testing services.

The cost and intermediary cost-effectiveness of oral HIV self-test kit distribution across 11 distribution models in South Africa.

BACKGROUND: Countries around the world seek innovative ways of closing their remaining gaps towards the target of 95% of people living with HIV (PLHIV) knowing their status by 2030. Offering kits allowing HIV self-testing (HIVST) in private might help close these gaps. METHODS: We analysed the cost, use and linkage to onward care of 11 HIVST kit distribution models alongside the Self-Testing AfRica Initiative's distribution of 2.2 million HIVST kits in South Africa in 2018/2019. Outcomes were based on telephonic surveys of 4% of recipients; costs on a combination of micro-costing, time-and-motion and expenditure analysis. Costs were calculated from the provider perspective in 2019 US$, as incremental costs in integrated and full costs in standalone models. RESULTS: HIV positivity among kit recipients was 4%-23%, with most models achieving 5%-6%. Linkage to confirmatory testing and antiretroviral therapy (ART) initiation for those screening positive was 19%-78% and 2%-72% across models. Average costs per HIVST kit distributed varied between $4.87 (sex worker model) and $18.07 (mobile integration model), with differences largely driven by kit volumes. HIVST kit costs (at $2.88 per kit) and personnel costs were the largest cost items throughout. Average costs per outcome increased along the care cascade, with the sex worker network model being the most cost-effective model across metrics used (cost per kit distributed/recipient screening positive/confirmed positive/initiating ART). Cost per person confirmed positive for HIVST was higher than standard HIV testing. CONCLUSION: HIV self-test distribution models in South Africa varied widely along four characteristics: distribution volume, HIV positivity, linkage to care and cost. Volume was highest in models that targeted public spaces with high footfall (flexible community, fixed point and transport hub distribution), followed by workplace models. Transport hub, workplace and sex worker models distributed kits in the least costly way. Distribution via index cases at facility as well as sex worker network distribution identified the highest number of PLHIV at lowest cost.

Implementation of different HIV self-testing models with implications for HIV testing services during the COVID-19 pandemic: study protocol for secondary data analysis of the STAR Initiative in South Africa.

INTRODUCTION: HIV self-testing (HIVST) presents a convenient, private approach that removes barriers to providing HIV testing services. The Self-Testing Africa (STAR) Initiative aims to scale up HIVST among priority and undertested populations. HIVST has the potential to help maintain testing services during the social distancing restrictions implemented to prevent the spread of COVID-19. This project evaluates linkage to confirmatory testing and treatment for HIV-positive clients for the STAR South Africa site. METHODS AND ANALYSIS: This secondary data analysis protocol aims to evaluate different HIVST distribution models from a prospective study implemented during November 2017 and December 2020 by Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute. Routinely collected distribution and self-reported HIVST outcomes data will be deidentified and analysed. The main outcomes of interest are linkage to care and treatment among HIVST users who report a reactive HIVST result. Additionally, we plan to determine sociodemographic factors associated with linkage to care and treatment among HIVST users. Descriptive statistics will be used to describe the variables of interest, and modified Poisson regression with robust variance estimation will be performed to identify factors associated with linkage to care and treatment among HIVST users who report a reactive HIVST result. Risk ratios and 95% CIs for the risk ratios will be reported. ETHICS AND DISSEMINATION: The study protocol has been approved by the University of Witwatersrand Human Research Ethics Committee. The dissemination plan for the study findings will include presentations to local and international health authorities, international conferences and publications in open access journals.

HIV prevalence and the cascade of care in five South African correctional facilities.

BACKGROUND: South Africa is home to the world's largest HIV epidemic. Throughout the world, incarcerated individuals have a higher prevalence of HIV than the general public, and South Africa has one of the highest rates of incarceration in sub-Saharan Africa. In spite of this, little has been published about the burden of HIV and how care is delivered in South African correctional facilities. OBJECTIVE: To estimate the prevalence of people living with HIV and identify initiation and retention in the HIV cascade of care across five correctional facilities. METHODS: Cross-sectional retrospective analysis of 30,571 adult inmates who participated in a tuberculosis screening and HIV counseling and testing campaign in South African correctional facilities (January 1, 2014-January 31, 2015). Descriptive statistics were used to estimate the proportion and 95% confidence intervals of HIV. Proportions of persons retained and lost at each step in the HIV cascade of care under this intervention were calculated. Poisson regression with robust variance estimates were used, and clustering by facility was accounted for in all analyses. RESULTS: Results of the screening campaign found previously undiagnosed HIV among 13.0% of those consenting to screening, with a total estimated HIV prevalence of 17.7% (n = 3,184, 95% CI: 17.2-18.3%) in the sample. When examining the overall cascade of care, 48.3% of those with HIV initiated care, and overall 45.6% of persons who entered care qualified for ART initiated treatment. A Poisson regression accounting for clustering by facility found HIV high risk groups within the population such as women (aRR = 1.72, 95% CI: 1.57, 1.89), those over 35 years of age (aRR = 2.43, 95% CI: 1.53, 3.85), and people incarcerated less than one year (aRR = 1.41, 95% CI: 1.19, 1.67). CONCLUSION: In this setting, routine screening is recommended, and measures are needed to ensure that persons diagnosed are adequately linked to and retained in care.

Implementing a large-scale systematic tuberculosis screening program in correctional facilities in South Africa.

Background. Tuberculosis (TB) prevalence is high in correctional facilities in southern Africa. With support from local South African nongovernmental organizations, the South African Department of Correctional Services initiated a program of systematically screening newly admitted and current inmates for symptoms followed by GeneXpert Mycobacterium tuberculosis (MTB)/rifampicin (Rif) for microbiologic testing of symptomatic inmates. Methods. We conducted a program evaluation during a 5-month window describing program reach, effectiveness, adoption within the facilities, cost, and opportunities for sustainability. This evaluation included 4 facilities (2 large and 2 smaller) with a total daily census of 20 700 inmates. Results. During the 5-month evaluation window from May to September 2013, 7426 inmates were screened at the 4 facilities. This represents screening 87% of all new admits (the remaining new admits were screened by correctional staff only and are not included in these statistics) and 23% of the daily inmate census, reaching 55% of the overall screening target as calculated per annum. The reach ranged from 57% screened during these 5 months at one of the smaller facilities to 13% at the largest facility. Two hundred one cases of pulmonary TB were diagnosed, representing 2.1% of the screened population; 93% had documented initiation of TB treatment. The cost per TB case identified was $1513, excluding treatment costs (with treatment costs it was $1880). Conclusions. We reached a large number of inmates with high-volume screening and effectively used GeneXpert MTB/Rif to diagnose pulmonary TB and rapidly initiate treatment. The cost was comparable to other screening programs.

Quinoline antimalarials containing a dibemethin group are active against chloroquinone-resistant Plasmodium falciparum and inhibit chloroquine transport via the P. falciparum chloroquine-resistance transporter (PfCRT).

A series of 4-amino-7-chloroquinolines with dibenzylmethylamine (dibemethin) side chains were shown to inhibit synthetic hemozoin formation. These compounds were equally active against cultures of chloroquine-sensitive (D10) and chloroquine-resistant (K1) Plasmodium falciparum. The most active compound had an IC(50) value comparable to that of chloroquine, and its potency was undiminished when tested in three additional chloroquine-resistant strains. The three most active compounds exhibited little or no cytotoxicity in a mammalian cell line. When tested in vivo against mouse malaria via oral administration, two of the dibemethin derivatives reduced parasitemia by over 99%, with mice treated at 100 mg/kg surviving the full length of the experiment. Three of the compounds were also shown to inhibit chloroquine transport via the parasite's chloroquine-resistance transporter (PfCRT) in a Xenopus oocyte expression system. This constitutes the first example of a dual-function antimalarial for which the ability to inhibit both hemozoin formation and PfCRT has been demonstrated directly.

A series of structurally simple chloroquine chemosensitizing dibemethin derivatives that inhibit chloroquine transport by PfCRT.

A series of 12 new dibemethin (N-benzyl-N-methyl-1-phenylmethanamine) derivatives bearing an N-aminomethyl group attached to the one phenyl ring and an H, Cl, OCH3 or N(CH3)2 group on the other have been synthesized. These compounds all showed strong chloroquine chemosensitizing activity, comparable to verapamil, when present at 1 µM in an in vitro culture of the chloroquine-resistant W2 strain of the human malaria parasite, Plasmodium falciparum. Their N-formylated derivatives also exhibited resistance-reversing activity, but only at substantially higher IC10 concentrations. A number of the dibemethin derivatives were shown to inhibit chloroquine transport via the parasite's 'chloroquine resistance transporter' (PfCRT) in a Xenopus laevis oocyte expression system. The reduced resistance-reversing activity of the formylated compounds relative to their free amine counterparts can probably be ascribed to two factors: decreased accumulation of the formylated dibemethins within the parasite's internal digestive vacuole (believed to be the site of action of chloroquine), and a reduced ability to inhibit PfCRT. The resistance-reversing activity of the compounds described here demonstrates that the amino group need not be attached to the two aromatic rings via a three or four carbon chain as has been suggested by previous QSAR studies. These compounds may be useful as potential side chains for attaching to a 4,7-dichloroquinoline group in order to generate new resistance-reversing chloroquine analogues with inherent antimalarial activity.

Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols.

BACKGROUND: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel remains the main drug used for schistosomiasis treatment, and reliance on the single therapy has been prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within the S. mansoni gut is a major heme detoxification route with lipid droplets involved in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of three antimalarial compounds, quinine (QN), quinidine (QND) and quinacrine (QCR) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. METHODOLOGY/PRINCIPAL FINDINGS: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN, and QND (75 mg/kg/day) from the 11(th) to 17(th) day after infection caused significant decreases in worm burden (39%-61%) and egg production (42%-98%). Hz formation was significantly inhibited (40%-65%) in female worms recovered from QN- and QND-treated mice and correlated with reduction in the female worm burden. We also observed that QN treatment promoted remarkable ultrastructural changes in male and female worms, particularly in the gut epithelium and reduced the granulomatous reaction to parasite eggs trapped in the liver. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. CONCLUSIONS: The overall significant reduction in several disease burden parameters by the antimalarial quinoline methanols indicates that interference with Hz formation in S. mansoni represents an important mechanism of schistosomicidal action of these compounds and points out the heme crystallization process as a valid chemotherapeutic target to treat schistosomiasis.