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.

User perspectives and preferences on a novel TB LAM diagnostic (Fujifilm SILVAMP TB LAM)-a qualitative study in Malawi and Zambia.

Widely available tuberculosis (TB) diagnostics use sputum samples. However, many patients, particularly children and patients living with HIV (PLHIV), struggle to provide sputum. Urine diagnostics are a promising approach to circumvent this challenge while delivering reliable and timely diagnosis. This qualitative study in two high TB/HIV burden countries assesses values and preferences of end-users, along with potential barriers for the implementation of the novel Fujifilm SILVAMP TB-LAM (FujiLAM, Fujifilm, Japan) urine test. Between September 2020 and March 2021, we conducted 42 semi-structured interviews with patients, health care providers (HCPs) and decision makers (DMs) (e.g., in national TB programs) in Malawi and Zambia. Interviews were transcribed verbatim and analyzed using a framework approach supported by NVIVO. Findings aligned with the pre-existing Health Equity Implementation Framework, which guided the presentation of results. The ease and convenience of urine-based testing was described as empowering among patients and HCPs who lamented the difficulty of sputum collection, however HCPs expressed concerns that a shift in agency to the patient may affect clinic workflows (e.g., due to less control over collection). Implementation facilitators, such as shorter turnaround times, were welcomed by operators and patients alike. The decentralization of diagnostics was considered possible with FujiLAM by HCPs and DMs due to low infrastructure requirements. Finally, our findings support efforts for eliminating the CD4 count as an eligibility criterion for LAM testing, to facilitate implementation and benefit a wider range of patients. Our study identified barriers and facilitators relevant to scale-up of urine LAM tests in Malawi and Zambia. FujiLAM could positively impact health equity, as it would particularly benefit patient groups currently underserved by existing TB diagnostics. Participants view the approach as a viable, acceptable, and likely sustainable option in low- and middle-income countries, though adaptations may be required to current health care processes for deployment. Trial registration: German Clinical Trials Register, DRKS00021003. URL: https://www.drks.de/drks_web/setLocale_EN.do.

Population benefits of addressing programmatic and social determinants of gender disparities in tuberculosis in Viet Nam: A modelling study.

High prevalence of infectious tuberculosis among men suggests potential population-wide benefits from addressing programmatic and social determinants of gender disparities. Utilising a sex-stratified compartmental transmission model calibrated to tuberculosis burden estimates for Viet Nam, we modelled interventions to increase active case finding, to reduce tobacco smoking, and to reduce alcohol consumption by 2025 in line with national and global targets. For each intervention, we examined scenarios differentially targeting men and women and evaluated impact on tuberculosis morbidity and mortality in men, women, and children in 2035. Active case finding interventions targeting men projected greater reductions in tuberculosis incidence in men, women, and children (16.2%, uncertainty interval, UI, 11.4-23.0%, 11.8%, UI 8.0-18.6%, and 21.5%, UI 16.9-28.5%, respectively) than those targeting women (5.2%, UI 3.8-7.1%, 5.4%, UI 3.9-7.3%, and 8.6%, UI 6.9-10.7%, respectively). Projected reductions in tuberculosis incidence for interventions to reduce male tobacco smoking and alcohol consumption were greatest for men (17.4%, UI 11.8-24.7%, and 11.0%, UI 5.4-19.4%, respectively), but still substantial for women (6.9%, UI 3.8-12.5%, and 4.4%, UI 1.9-10.6%, respectively) and children (12.7%, UI 8.4-19.0%, and 8.0%, UI 3.9-15.0%, respectively). Comparable interventions targeting women projected limited impact, with declines of 0.3% (UI 0.2%-0.3%) and 0.1% (UI 0.0%-0.1%), respectively. Addressing programmatic and social determinants of men's tuberculosis burden has population-wide benefits. Future interventions to increase active case finding, to reduce tobacco smoking, and to reduce harmful alcohol consumption, whilst not ignoring women, should focus on men to most effectively reduce tuberculosis morbidity and mortality in men, women, and children.

Computer-aided X-ray screening for tuberculosis and HIV testing among adults with cough in Malawi (the PROSPECT study): A randomised trial and cost-effectiveness analysis.

BACKGROUND: Suboptimal tuberculosis (TB) diagnostics and HIV contribute to the high global burden of TB. We investigated costs and yield from systematic HIV-TB screening, including computer-aided digital chest X-ray (DCXR-CAD). METHODS AND FINDINGS: In this open, three-arm randomised trial, adults (≥18 years) with cough attending acute primary services in Malawi were randomised (1:1:1) to standard of care (SOC); oral HIV testing (HIV screening) and linkage to care; or HIV testing and linkage to care plus DCXR-CAD with sputum Xpert for high CAD4TBv5 scores (HIV-TB screening). Participants and study staff were not blinded to intervention allocation, but investigator blinding was maintained until final analysis. The primary outcome was time to TB treatment. Secondary outcomes included proportion with same-day TB treatment; prevalence of undiagnosed/untreated bacteriologically confirmed TB on day 56; and undiagnosed/untreated HIV. Analysis was done on an intention-to-treat basis. Cost-effectiveness analysis used a health-provider perspective. Between 15 November 2018 and 27 November 2019, 8,236 were screened for eligibility, with 473, 492, and 497 randomly allocated to SOC, HIV, and HIV-TB screening arms; 53 (11%), 52 (9%), and 47 (9%) were lost to follow-up, respectively. At 56 days, TB treatment had been started in 5 (1.1%) SOC, 8 (1.6%) HIV screening, and 15 (3.0%) HIV-TB screening participants. Median (IQR) time to TB treatment was 11 (6.5 to 38), 6 (1 to 22), and 1 (0 to 3) days (hazard ratio for HIV-TB versus SOC: 2.86, 1.04 to 7.87), with same-day treatment of 0/5 (0%) SOC, 1/8 (12.5%) HIV, and 6/15 (40.0%) HIV-TB screening arm TB patients (p = 0.03). At day 56, 2 SOC (0.5%), 4 HIV (1.0%), and 2 HIV-TB (0.5%) participants had undiagnosed microbiologically confirmed TB. HIV screening reduced the proportion with undiagnosed or untreated HIV from 10 (2.7%) in the SOC arm to 2 (0.5%) in the HIV screening arm (risk ratio [RR]: 0.18, 0.04 to 0.83), and 1 (0.2%) in the HIV-TB screening arm (RR: 0.09, 0.01 to 0.71). Incremental costs were US$3.58 and US$19.92 per participant screened for HIV and HIV-TB; the probability of cost-effectiveness at a US$1,200/quality-adjusted life year (QALY) threshold was 83.9% and 0%. Main limitations were the lower than anticipated prevalence of TB and short participant follow-up period; cost and quality of life benefits of this screening approach may accrue over a longer time horizon. CONCLUSIONS: DCXR-CAD with universal HIV screening significantly increased the timeliness and completeness of HIV and TB diagnosis. If implemented at scale, this has potential to rapidly and efficiently improve TB and HIV diagnosis and treatment. TRIAL REGISTRATION: clinicaltrials.gov NCT03519425.

Community-based HIV self-testing: a cluster-randomised trial of supply-side financial incentives and time-trend analysis of linkage to antiretroviral therapy in Zimbabwe.

BACKGROUND: HIV self-testing (HIVST) requires linkage to post-test services to maximise its benefits. We evaluated effect of supply-side incentivisation on linkage following community-based HIVST and evaluated time-trends in facility-based antiretroviral therapy (ART) initiations. METHODS: From August 2016 to August 2017 community-based distributors (CBDs) in 38 rural Zimbabwean communities distributed HIVST door-to-door in 19-25 day campaigns. Communities were allocated (1:1) using constrained randomisation to either one-off US$50 remuneration per CBD (non-incentive arm), or US$50 plus US$0.20 incentive per client visiting mobile-outreach services (conditional-incentive arm). The primary outcome, assessed by population survey 6 weeks later, was self-reported uptake of any clinic service, analysed with random-effects logistic regression. Separately, non-randomised difference-in-differences in monthly ART initiations were analysed for three time periods (6 months baseline; HIVST campaign; 3 months after) at public clinics with (40 clinics) and without (124 clinics) HIVST distribution in catchment area. FINDINGS: A total of 445 conditional-incentive CBDs distributed 39 205 HIVST kits (mean/CBD: 88; 95% CI: 85 to 92) and 447 non-incentive CBDs distributed 41 173 kits (mean/CBD: 93; 95% CI: 89 to 96). Survey participation was 7146/8566 (83.4%), with 3593 (50.3%) reporting self-testing including 1305 (18.3%) previously untested individuals. Use of clinic services post-HIVST was similar in conditional-incentive (1062/3698, 28.7%) and non-incentive (1075/3448, 31.2%) arms (adjusted risk ratio (aRR) 0.94, 95% CI: 0.86 to 1.03). Confirmatory testing by newly diagnosed/untreated HIVST+clients was, however, higher (conditional-incentive: 25/33, 75.8% vs non-incentive: 20/40, 50.0%: aRR: 1.59, 95% CI: 1.05 to 2.39). In total, 12 808 ART initiations occurred, with no baseline or postcampaign differences between initiation rates in HIVST versus non-HIVST clinics, but initiation rates increased from 7.31 to 9.59 initiations per month in HIVST clinics during distribution, aRR: 1.27, 95% CI 1.17 to 1.39. CONCLUSIONS: Community-based HIVST campaigns achieved high testing uptake, temporally associated with increased demand for ART. Small supply-side incentives did not affect general clinic usage but may have increased confirmatory testing for newly diagnosed HIVST positive participants. TRIAL REGISTRATION NUMBER: PACTR201607001701788.

Pragmatic economic evaluation of community-led delivery of HIV self-testing in Malawi.

INTRODUCTION: Community-based strategies can extend coverage of HIV testing and diagnose HIV at earlier stages of infection but can be costly to implement. We evaluated the costs and effects of community-led delivery of HIV self-testing (HIVST) in Mangochi District, Malawi. METHODS: This economic evaluation was based within a pragmatic cluster-randomised trial of 30 group village heads and their catchment areas comparing the community-led HIVST intervention in addition to the standard of care (SOC) versus the SOC alone. The intervention involved mobilising community health groups to lead 7-day HIVST campaigns including distribution of HIVST kits. The SOC included facility-based HIV testing services. Primary costings estimated economic costs of the intervention and SOC from the provider perspective, with costs annualised and measured in 2018 US$. A postintervention survey captured individual-level data on HIV testing events, which were combined with unit costs from primary costings, and outcomes. The incremental cost per person tested HIV-positive and associated uncertainty were estimated. RESULTS: Overall, the community-led HIVST intervention costed $138 624 or $5.70 per HIVST kit distributed, with test kits and personnel the main contributing costs. The SOC costed $263 400 or $4.57 per person tested. Individual-level provider costs were higher in the community-led HIVST arm than the SOC arm (adjusted mean difference $3.77, 95% CI $2.44 to $5.10; p<0.001), while the intervention effect on HIV positivity varied based on adjustment for previous diagnosis. The incremental cost per person tested HIV positive was $324 but increased to $1312 and $985 when adjusting for previously diagnosed self-testers or self-testers on treatment, respectively. Community-led HIVST demonstrated low probability of being cost-effective against plausible willingness-to-pay values, with HIV positivity a key determinant. CONCLUSION: Community-led HIVST can provide HIV testing at a low additional unit cost. However, adding community-led HIVST to the SOC was not likely to be cost-effective, especially in contexts with low prevalence of undiagnosed HIV. TRIAL REGISTRATION NUMBER: NCT03541382.

Costs of integrating HIV self-testing in public health facilities in Malawi, South Africa, Zambia and Zimbabwe.

INTRODUCTION: As countries approach the UNAIDS 95-95-95 targets, there is a need for innovative and cost-saving HIV testing approaches that can increase testing coverage in hard-to-reach populations. The HIV Self-Testing Africa-Initiative distributed HIV self-test (HIVST) kits using unincentivised HIV testing counsellors across 31 public facilities in Malawi, South Africa, Zambia and Zimbabwe. HIVST was distributed either through secondary (partner's use) distribution alone or primary (own use) and secondary distribution approaches. METHODS: We evaluated the costs of adding HIVST to existing HIV testing from the providers' perspective in the 31 public health facilities across the four countries between 2018 and 2019. We combined expenditure analysis and bottom-up costing approaches. We also carried out time-and-motion studies on the counsellors to estimate the human resource costs of introducing and demonstrating how to use HIVST for primary and secondary use. RESULTS: A total of 41 720 kits were distributed during the analysis period, ranging from 1254 in Zimbabwe to 27 678 in Zambia. The cost per kit distributed through the primary distribution approach was $4.27 in Zambia and $9.24 in Zimbabwe. The cost per kit distributed through the secondary distribution approach ranged from $6.46 in Zambia to $13.42 in South Africa, with a wider variation in the average cost at facility-level. From the time-and-motion observations, the counsellors spent between 20% and 44% of the observed workday on HIVST. Overall, personnel and test kit costs were the main cost drivers. CONCLUSION: The average costs of distributing HIVST kits were comparable across the four countries in our analysis despite wide cost variability within countries. We recommend context-specific exploration of potential efficiency gains from these facility-level cost variations and demand creation activities to ensure continued affordability at scale.

Modelling costs of community-based HIV self-testing programmes in Southern Africa at scale: an econometric cost function analysis across five countries.

BACKGROUND: Following success demonstrated with the HIV Self-Testing AfRica Initiative, HIV self-testing (HIVST) is being added to national HIV testing strategies in Southern Africa. An analysis of the costs of scaling up HIVST is needed to inform national plans, but there is a dearth of evidence on methods for forecasting costs at scale from pilot projects. Econometric cost functions (ECFs) apply statistical inference to predict costs; however, we often do not have the luxury of collecting large amounts of location-specific data. We fit an ECF to identify key drivers of costs, then use a simpler model to guide cost projections at scale. METHODS: We estimated the full economic costs of community-based HIVST distribution in 92 locales across Malawi, Zambia, Zimbabwe, South Africa and Lesotho between June 2016 and June 2019. We fitted a cost function with determinants related to scale, locales organisational and environmental characteristics, target populations, and per capita Growth Domestic Product (GDP). We used models differing in data intensity to predict costs at scale. We compared predicted estimates with scale-up costs in Lesotho observed over a 2-year period. RESULTS: The scale of distribution, type of community-based intervention, percentage of kits distributed to men, distance from implementer's warehouse and per capita GDP predicted average costs per HIVST kit distributed. Our model simplification approach showed that a parsimonious model could predict costs without losing accuracy. Overall, ECF showed a good predictive capacity, that is, forecast costs were close to observed costs. However, at larger scale, variations of programme efficiency over time (number of kits distributed per agent monthly) could potentially influence cost predictions. DISCUSSION: Our empirical cost function can inform community-based HIVST scale-up in Southern African countries. Our findings suggest that a parsimonious ECF can be used to forecast costs at scale in the context of financial planning and budgeting.

Partner-delivered HIV self-test kits with and without financial incentives in antenatal care and index patients with HIV in Malawi: a three-arm, cluster-randomised controlled trial.

BACKGROUND: Secondary distribution of HIV self-testing (HIVST) kits by patients attending clinic services to their partners could improve the rate of HIV diagnosis. We aimed to investigate whether secondary administration of HIVST kits, with or without an additional financial incentive, via women receiving antenatal care (ANC) or via people newly diagnosed with HIV (ie, index patients) could improve the proportion of male partners tested or the number of people newly diagnosed with HIV. METHODS: We did a three-arm, open-label, pragmatic, cluster-randomised trial of 27 health centres (clusters), eligible if they were a government primary health centre providing ANC, HIV testing, and ART services, across four districts of Malawi. We recruited women (aged ≥18 years) attending their first ANC visit and whose male partner was available, not already taking ART, and not already tested for HIV during this pregnancy (ANC cohort), and people (aged ≥18 years) with newly diagnosed HIV during routine clinic HIV testing who had at least one sexual contact not already known to be HIV-positive (index cohort). Centres were randomly assigned (1:1:1), using a public selection of computer-generated random allocations, to enhanced standard of care (including an invitation for partners to attend HIV testing services), HIVST only, or HIVST plus a US$10 financial incentive for retesting. The primary outcome for the ANC cohort was the proportion of male partners reportedly tested, as ascertained by interview with women in this cohort at day 28. The primary outcome for the index cohort was the geometric mean number of new HIV-positive people identified per facility within 28 days of enrolment, as measured by observed HIV test results. Cluster-level summaries compared intervention with standard of care by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03705611. FINDINGS: Between Sept 8, 2018, and May 2, 2019, nine clusters were assigned to each trial arm, resulting in 4544 eligible women in the ANC cohort (1447 [31·8%] in the standard care group, 1465 [32·2%] in the HIVST only group, and 1632 [35·9%] in HIVST plus financial incentive group) and 708 eligible patients in the index cohort (234 [33·1%] in the standard care group, 169 [23·9%] in the HIVST only group, and 305 [42·9%] in the HIVST plus financial incentive group). 4461 (98·2%) of 4544 eligible women in the ANC cohort and 645 (91·1%) of 708 eligible patients in the index cohort were recruited, of whom 3378 (75·7%) in the ANC cohort and 439 (68·1%) in the index cohort were interviewed after 28 days. In the ANC cohort, the mean proportion of reported partner testing per cluster was 35·0% (SD 10·0) in the standard care group, 73·0% in HIVST only group (13·1, adjusted risk ratio [RR] 1·71, 95% CI 1·48-1·98; p<0·0001), and 65·2% in the HIVST plus financial incentive group (11·6, adjusted RR 1·62, 1·45-1·81; p<0·0001). In the index cohort, the geometric mean number of new HIV-positive sexual partners per cluster was 1·35 (SD 1·62) for the standard care group, 1·91 (1·78) for the HIVST only group (incidence rate ratio adjusted for number eligible as an offset in the negative binomial model 1·65, 95% CI 0·49-5·55; p=0·3370), and 3·20 (3·81) for the HIVST plus financial incentive group (3·11, 0·99-9·77; p=0·0440). Four self-resolving, temporary marital separations occurred due to disagreement in couples regarding HIV self-test kits. INTERPRETATION: Although administration of HIVST kits in the ANC cohort, even when offered alongside a financial incentive, did not identify significantly more male patients with HIV than did standard care, out-of-clinic options for HIV testing appear more acceptable to many male partners of women with HIV, increasing test uptake. Viewed in the current context, this approach might allow continuation of services despite COVID-19-related lockdowns. FUNDING: Unitaid, through the Self-Testing Africa Initiative.

Effect of community-led delivery of HIV self-testing on HIV testing and antiretroviral therapy initiation in Malawi: A cluster-randomised trial.

BACKGROUND: Undiagnosed HIV infection remains substantial in key population subgroups including adolescents, older adults, and men, driving ongoing transmission in sub-Saharan Africa. We evaluated the impact, safety, and costs of community-led delivery of HIV self-testing (HIVST), aiming to increase HIV testing in underserved subgroups and stimulate demand for antiretroviral therapy (ART). METHODS AND FINDINGS: This cluster-randomised trial, conducted between October 2018 and July 2019, used restricted randomisation (1:1) to allocate 30 group village head clusters in Mangochi district, Malawi to the community-led HIVST intervention in addition to the standard of care (SOC) or the SOC alone. The intervention involved mobilising community health groups to lead the design and implementation of 7-day HIVST campaigns, with cluster residents (≥15 years) eligible for HIVST. The primary outcome compared lifetime HIV testing among adolescents (15 to 19 years) between arms. Secondary outcomes compared: recent HIV testing (in the last 3 months) among older adults (≥40 years) and men; cumulative 6-month incidence of ART initiation per 100,000 population; knowledge of the preventive benefits of HIV treatment; and HIV testing stigma. Outcomes were measured through a post-intervention survey and at neighboring health facilities. Analysis used intention-to-treat for cluster-level outcomes. Community health groups delivered 24,316 oral fluid-based HIVST kits. The survey included 90.2% (3,960/4,388) of listed participants in the 15 community-led HIVST clusters and 89.2% (3,920/4,394) of listed participants in the 15 SOC clusters. Overall, the proportion of men was 39.0% (3,072/7,880). Most participants obtained primary-level education or below, were married, and reported a sexual partner. Lifetime HIV testing among adolescents was higher in the community-led HIVST arm (84.6%, 770/910) than the SOC arm (67.1%, 582/867; adjusted risk difference [RD] 15.2%, 95% CI 7.5% to 22.9%; p < 0.001), especially among 15 to 17 year olds and boys. Recent testing among older adults was also higher in the community-led HIVST arm (74.5%, 869/1,166) than the SOC arm (31.5%, 350/1,111; adjusted RD 42.1%, 95% CI 34.9% to 49.4%; p < 0.001). Similarly, the proportions of recently tested men were 74.6% (1,177/1,577) and 33.9% (507/1,495) in the community-led HIVST and SOC arms, respectively (adjusted RD 40.2%, 95% CI 32.9% to 47.4%; p < 0.001). Knowledge of HIV treatment benefits and HIV testing stigma showed no differences between arms. Cumulative incidence of ART initiation was respectively 305.3 and 226.1 per 100,000 population in the community-led HIVST and SOC arms (RD 72.3, 95% CI -36.2 to 180.8; p = 0.18). In post hoc analysis, ART initiations in the 3-month post-intervention period were higher in the community-led HIVST arm than the SOC arm (RD 97.7, 95% CI 33.4 to 162.1; p = 0.004). HIVST uptake was 74.7% (2,956/3,960), with few adverse events (0.6%, 18/2,955) and at US$5.70 per HIVST kit distributed. The main limitations include the use of self-reported HIV testing outcomes and lack of baseline measurement for the primary outcome. CONCLUSIONS: In this study, we found that community-led HIVST was effective, safe, and affordable, with population impact and coverage rapidly realised at low cost. This approach could enable community HIV testing in high HIV prevalence settings and demonstrates potential for economies of scale and scope. TRIAL REGISTRATION: Clinicaltrials.gov NCT03541382.

Using HIV self-testing to increase the affordability of community-based HIV testing services.

OBJECTIVES: This study estimates the costs of community-based HIV testing services (HTS) in Lesotho and assesses the potential efficiency gains achieved by adding HIV self-testing (HIVST) and then self-testing booths. DESIGN: Micro-costing analysis using longitudinal data from a real-world intervention. METHODS: We collected data prospectively on provider's costs and programmatic outcomes over three time periods of approximately 8 months each, between May 2017 and April 2019. The scope of services was extended during each period as follows: HTS only, HTS and HIVST, HTS and HIVST with individual HIVST booths wherein clients were encouraged to self-test on-site followed by on-site confirmative testing for those with reactive self-test. For each implementation period, we estimated the full financial and economic implementation costs, the incremental costs of adding HIVST onto conventional HTS and the cost per HIV positive case identified. RESULTS: Costs per HIV-positive case identified increased between period 1 (US$956) and period 2 (US$1249) then dropped in period 3 (US$813). Full versus incremental cost analyses resulted in large differences in the magnitude of costs, attributable to methods rather than resource use: for example, in period 3, the average full and incremental cost estimates for HTS were US$34.3 and US$23.5 per person tested, and for HIVST were US$37.7 and US$14.0 per kit provided, respectively. CONCLUSION: In Lesotho, adding HIVST to community-based HTS improves its overall affordability for HIV-positive case finding. The reporting of both full and incremental cost estimates increase transparency for use in priority setting, budgeting and financial planning for scale-up.

Provider-initiated HIV testing and TB screening in the era of universal coverage: Are the right people being reached? A cohort study in Blantyre, Malawi.

INTRODUCTION: Patients with tuberculosis (TB) symptoms have high prevalence of HIV, and should be prioritised for HIV testing. METHODS: In a prospective cohort study in Bangwe primary care clinic, Blantyre, Malawi, all adults (18 years or older) presenting with an acute illness were screened for TB symptoms (cough, fever, night sweats, weight loss). Demographic characteristics were linked to exit interview by fingerprint bioidentification. Multivariable logistic regression models were constructed to estimate the proportion completing same-visit HIV testing, comparing between those with and without TB symptoms. RESULTS: There were 5427 adult attendees between 21/5/2018 and 6/9/2018. Exit interviews were performed for 2402 (44%). 276 patients were excluded from the analysis, being already on antiretroviral therapy (ART). Presentation with any TB symptom was common for men (54.6%) and women (57.4%). Overall 27.6% (585/ 2121) attenders reported being offered testing and 21.5% (455/2121) completed provider-initiated HIV testing and counselling (PITC) and received results. The proportions offered testing were similar among participants with and without TB symptoms (any TB symptom: 29.0% vs. 25.7%). This was consistent for each individual symptom; cough, weight loss, fever and night sweats. Multivariable regression models indicated men, younger adults and participants who had previously tested were more likely to complete PITC than women, older adults and those who had never previously tested. CONCLUSIONS: Same-visit completion of HIV testing was suboptimal, especially among groups known to have high prevalence of undiagnosed HIV. As countries approach universal coverage of ART, identifying and prioritising currently underserved groups for HIV testing will be essential.

Patient-incurred cost of inpatient treatment for Tuberculosis in rural Malawi.

OBJECTIVES: To mitigate the economic burden of tuberculosis (TB), it is important to fully understand the costs of TB treatment from the patient perspective. We therefore sought to quantify the patient-incurred cost of TB treatment in rural Malawi, with specific focus on costs borne by patients requiring inpatient hospitalisation. METHODS: We conducted a cross-sectional survey of 197 inpatients and 156 outpatients being treated for TB in rural Malawi. We collected data on out-of-pocket costs and lost wages, including costs to guardians. Costs for inpatient TB treatment were estimated and compared to costs for outpatient TB treatment. We then explored the equity distribution of inpatient TB treatment cost using concentration curves. RESULTS: Despite free government services, inpatients were estimated to incur a mean of $137 (standard deviation: $147) per initial TB episode, corresponding to >50% of annual household spending among patients in the lowest expenditure quintile. Non-medical hospitalisation costs accounted for 88% of this total. Patients treated entirely as outpatients incurred estimated costs of $25 (standard deviation: $15) per episode. The concentration curves showed that, among individuals hospitalised for an initial TB episode, poorer patients shouldered a much greater proportion of inpatient TB treatment costs than wealthier ones (concentration index: -0.279). CONCLUSION: Patients hospitalised for TB in resource-limited rural Malawi experience devastating costs of TB treatment. Earlier diagnosis and treatment must be prioritised if we are to meet goals of effective TB control, avoidance of catastrophic costs and provision of appropriate patient-centred care in such settings.

OBJECTIFS: Pour atténuer la charge économique de la tuberculose (TB), il est important de bien comprendre les coûts du traitement de la TB du point de vue du patient. Nous avons donc cherché à quantifier les coûts encourus par les patients pour le traitement de la TB dans les zones rurales du Malawi, en mettant l'accent sur les coûts supportés par les patients nécessitant une hospitalisation. MÉTHODES: Nous avons mené une enquête transversale auprès de 197 patients hospitalisés et 156 patients ambulatoires traités pour la TB dans les régions rurales du Malawi. Nous avons collecté des données sur les dépenses payées directement de la poche et les pertes de salaire, y compris les coûts pour les gardiens des malades. Les coûts du traitement anti-TB des patients hospitaliser ont été estimés et comparés aux ceux des patients ambulatoires. Nous avons ensuite exploré la répartition des équités propres au coût du traitement de la TB des patients hospitalisés en utilisant des courbes de concentration. RÉSULTATS: Malgré les services gratuits du gouvernement, les patients hospitalisés encouraient en moyenne estimée de 137 $ (écart-type: 147 $) par épisode initial de TB, ce qui correspond à >50% des dépenses annuelles des ménages chez les patients du quintile de dépenses le plus bas. Les frais d'hospitalisation non médicaux représentaient 88% de ce total. Les patients traités entièrement en ambulatoire encouraient des coûts estimés à 25 $ (écart type: 15 $) par épisode. Les courbes de concentration ont montré que, parmi les personnes hospitalisées pour un premier épisode de TB, les patients les plus pauvres supportaient une proportion beaucoup plus élevée des coûts de traitement de la TB en hospitalisation que les plus riches (indice de concentration: -0,279). CONCLUSION: Les patients hospitalisés pour la TB dans les régions rurales pauvres du Malawi connaissent des coûts dévastateurs pour le traitement de la TB. Le diagnostic et le traitement précoces doivent être priorisés si nous voulons atteindre des objectifs de contrôle efficace de la TB, d'évitement des coûts catastrophiques et de prestation de soins appropriés centrés sur le patient dans de tels contextes .

Community-led delivery of HIV self-testing to improve HIV testing, ART initiation and broader social outcomes in rural Malawi: study protocol for a cluster-randomised trial.

BACKGROUND: Prevention of new HIV infections is a critical public health issue. The highest HIV testing gaps are in men, adolescents 15-19 years old, and adults 40 years and older. Community-based HIV testing services (HTS) can contribute to increased testing coverage and early HIV diagnosis, with HIV self-testing (HIVST) strategies showing promise. Community-based strategies, however, are resource intensive, costly and not widely implemented. A community-led approach to health interventions involves supporting communities to plan and implement solutions to improve their health. This trial aims to determine if community-led delivery of HIVST can improve HIV testing uptake, ART initiation, and broader social outcomes in rural Malawi. METHODS: The trial uses a parallel arm, cluster-randomised design with group village heads (GVH) and their defined catchment areas randomised (1:1) to community-led HIVST or continue with the standard of the care (SOC). As part of the intervention, informal community health cadres are supported to plan and implement a seven-day HIVST campaign linked to HIV treatment and prevention. Approximately 12 months after the initial campaign, intervention GVHs are randomised to lead a repeat HIVST campaign. The primary outcome includes the proportion of adolescents 15-19 years old who have tested for HIV in their lifetime. Secondary outcomes include recent testing in adults 40 years and older and men; ART initiation; knowledge of HIV prevention; and HIV testing stigma. Outcomes will be measured through cross-sectional surveys and clinic registers. Economic evaluation will determine the cost per person tested, cost per person diagnosed, and incremental cost effectiveness ratio. DISCUSSION: To the best of our knowledge, this is the first trial to assess the effectiveness of community-led HTS, which has only recently been enabled by the introduction of HIVST. Community-led delivery of HIVST is a promising new strategy for providing periodic HIV testing to support HIV prevention in rural communities. Further, introduction of HIVST through a community-led framework seems particularly apt, with control over healthcare concurrently devolved to individuals and communities. TRIAL REGISTRATION: Clinicaltrials.gov registry ( NCT03541382 ) registered 30 May 2018.

The impact and cost-effectiveness of community-based HIV self-testing in sub-Saharan Africa: a health economic and modelling analysis.

INTRODUCTION: The prevalence of undiagnosed HIV is declining in Africa, and various HIV testing approaches are finding lower positivity rates. In this context, the epidemiological impact and cost-effectiveness of community-based HIV self-testing (CB-HIVST) is unclear. We aimed to assess this in different sub-populations and across scenarios characterized by different adult HIV prevalence and antiretroviral treatment programmes in sub-Saharan Africa. METHODS: The synthesis model was used to address this aim. Three sub-populations were considered for CB-HIVST: (i) women having transactional sex (WTS); (ii) young people (15 to 24 years); and (iii) adult men (25 to 49 years). We assumed uptake of CB-HIVST similar to that reported in epidemiological studies (base case), or assumed people use CB-HIVST only if exposed to risk (condomless sex) since last HIV test. We also considered a five-year time-limited CB-HIVST programme. Cost-effectiveness was defined by an incremental cost-effectiveness ratio (ICER; cost-per-disability-adjusted life-year (DALY) averted) below US$500 over a time horizon of 50 years. The efficiency of targeted CB-HIVST was evaluated using the number of additional tests per infection or death averted. RESULTS: In the base case, targeting adult men with CB-HIVST offered the greatest impact, averting 1500 HIV infections and 520 deaths per year in the context of a simulated country with nine million adults, and impact could be enhanced by linkage to voluntary medical male circumcision (VMMC). However, the approach was only cost-effective if the programme was limited to five years or the undiagnosed prevalence was above 3%. CB-HIVST to WTS was the most cost-effective. The main drivers of cost-effectiveness were the cost of CB-HIVST and the prevalence of undiagnosed HIV. All other CB-HIVST scenarios had an ICER above US$500 per DALY averted. CONCLUSIONS: CB-HIVST showed an important epidemiological impact. To maximize population health within a fixed budget, CB-HIVST needs to be targeted on the basis of the prevalence of undiagnosed HIV, sub-population and the overall costs of delivering this testing modality. Linkage to VMMC enhances its cost-effectiveness.

Economic cost analysis of door-to-door community-based distribution of HIV self-test kits in Malawi, Zambia and Zimbabwe.

INTRODUCTION: HIV self-testing (HIVST) is recommended by the World Health Organization in addition to other testing modalities to increase uptake of HIV testing, particularly among harder-to-reach populations. This study provides the first empirical evidence of the costs of door-to-door community-based HIVST distribution in Malawi, Zambia and Zimbabwe. METHODS: HIVST kits were distributed door-to-door in 71 sites across Malawi, Zambia and Zimbabwe from June 2016 to May 2017. Programme expenditures, supplemented by on-site observation and monitoring and evaluation data were used to estimate total economic and unit costs of HIVST distribution, by input and site. Inputs were categorized into start-up, capital and recurrent costs. Sensitivity and scenario analyses were performed to assess the impact of key parameters on unit costs. RESULTS: In total, 152,671, 103,589 and 93,459 HIVST kits were distributed in Malawi, Zambia and Zimbabwe over 12, 11 and 10 months respectively. Across these countries, 43% to 51% of HIVST kits were distributed to men. The average cost per HIVST kit distributed was US$8.15, US$16.42 and US$13.84 in Malawi, Zambia and Zimbabwe, respectively, with pronounced intersite variation within countries driven largely by site-level fixed costs. Site-level recurrent costs were 70% to 92% of full costs and 20% to 62% higher than routine HIV testing services (HTS) costs. Personnel costs contributed from 26% to 52% of total costs across countries reflecting differences in remuneration approaches and country GDP. CONCLUSIONS: These early door-to-door community HIVST distribution programmes show large potential, both for reaching untested populations and for substantial economies of scale as HIVST programmes scale-up and mature. From a societal perspective, the costs of HIVST appear similar to conventional HTS, with the higher providers' costs substantially offsetting user costs. Future approaches to minimizing cost and/or maximize testing coverage could include unpaid door-to-door community-led distribution to reach end-users and integrating HIVST into routine clinical services via direct or secondary distribution strategies with lower fixed costs.

Optimizing HIV testing services in sub-Saharan Africa: cost and performance of verification testing with HIV self-tests and tests for triage.

INTRODUCTION: Strategies employing a single rapid diagnostic test (RDT) such as HIV self-testing (HIVST) or "test for triage" (T4T) are proposed to increase HIV testing programme impact. Current guidelines recommend serial testing with two or three RDTs for HIV diagnosis, followed by retesting with the same algorithm to verify HIV-positive status before anti-retroviral therapy (ART) initiation. We investigated whether clients presenting to HIV testing services (HTS) following a single reactive RDT must undergo the diagnostic algorithm twice to diagnose and verify HIV-positive status, or whether a diagnosis with the setting-specific algorithm is adequate for ART initiation. METHODS: We calculated (1) expected number of false-positive (FP) misclassifications per 10,000 HIV negative persons tested, (2) positive predictive value (PPV) of the overall HIV testing strategy compared to the WHO recommended PPV ≥99%, and (3) expected cost per FP misclassified person identified by additional verification testing in a typical low-/middle-income setting, compared to the expected lifetime ART cost of $3000. Scenarios considered were as follows: 10% prevalence using two serial RDTs for diagnosis, 1% prevalence using three serial RDTs, and calibration using programmatic data from Malawi in 2017 where the proportion of people testing HIV positive in facilities was 4%. RESULTS: In the 10% HIV prevalence setting with a triage test, the expected number of FP misclassifications was 0.86 per 10,000 tested without verification testing and the PPV was 99.9%. In the 1% prevalence setting, expected FP misclassifications were 0.19 with 99.8% PPV, and in the Malawi 2017 calibrated setting the expected misclassifications were 0.08 with 99.98% PPV. The cost per FP identified by verification testing was $5879, $3770, and $24,259 respectively. Results were sensitive to assumptions about accuracy of self-reported reactive results and whether reactive triage test results influenced biased interpretation of subsequent RDT results by the HTS provider. CONCLUSIONS: Diagnosis with the full algorithm following presentation with a reactive triage test is expected to achieve PPV above the 99% threshold. Continuing verification testing prior to ART initiation remains recommended, but HIV testing strategies involving HIVST and T4T may provide opportunities to maintain quality while increasing efficiency as part of broader restructuring of HIV testing service delivery.

Exploring social harms during distribution of HIV self-testing kits using mixed-methods approaches in Malawi.

INTRODUCTION: HIV self-testing (HIVST) provides couples and individuals with a discreet, convenient and empowering testing option. As with all HIV testing, potential harms must be anticipated and mitigated to optimize individual and public health benefits. Here, we describe social harms (SHs) reported during HIVST implementation in Malawi, and propose a framework for grading and responding to harms, according to their severity. METHODS: We report findings from six HIVST implementation studies in Malawi (2011 to 2017) that included substudies investigating SH reports. Qualitative methods included focus group discussions, in-depth interviews and critical incident interviews. Earlier studies used intensive quantitative methods (post-test questionnaires for intimate partner violence, household surveys, investigation of all deaths in HIVST communities). Later studies used post-marketing reporting with/without community engagement. Pharmacovigilance methodology (whereby potentially life-threatening/changing events are defined as "serious") was used to grade SH severity, assuming more complete passive reporting for serious events. RESULTS: During distribution of 175,683 HIVST kits, predominantly under passive SH reporting, 25 serious SHs were reported from 19 (0.011%) self-testers, including 15 partners in eight couples with newly identified HIV discordancy, and one perinatally infected adolescent. There were no deaths or suicides. Marriage break-up was the most commonly reported serious SH (sixteen individuals; eight couples), particularly among serodiscordant couples. Among new concordant HIV-positive couples, blame and frustration was common but rarely (one episode) led to serious SHs. Among concordant HIV-negative couples, increased trust and stronger relationships were reported. Coercion to test or disclose was generally considered "well-intentioned" within established couples. Women felt empowered and were assertive when offering HIVST test kits to their partners. Some women who persuaded their partner to test, however, did report SHs, including verbal or physical abuse and economic hardship. CONCLUSIONS: After more than six years of large-scale HIVST implementation and in-depth investigation of SHs in Malawi, we identified approximately one serious reported SH per 10,000 HIVST kits distributed, predominantly break-up of married serodiscordant couples. Both "active" and "passive" reporting systems identified serious SH events, although with more complete capture by "active" systems. As HIVST is scaled-up, efforts to support and further optimize community-led SH monitoring should be prioritized alongside HIVST distribution.

The Self-Testing AfRica (STAR) Initiative: accelerating global access and scale-up of HIV self-testing.

INTRODUCTION: HIV self-testing (HIVST) was first proposed as an additional option to standard HIV testing services in the 1980s. By 2015, two years after the first HIVST kit was approved for the American market and the year in which Unitaid invested in the "HIV Self-Testing AfRica (STAR) Initiative," HIVST remained unexplored with negligible access in low- and middle-income countries (LMIC). However, rapid progress had been made. This commentary outlines the interlinked market, regulatory and policy barriers that had inhibited product development and kept HIVST out of LMIC policy. We detail the components of STAR that enabled rapid HIVST scale-up, including critical investments in implementation, research, market forecasting, and engagement with manufacturers and regulators. DISCUSSION: The STAR Initiative has generated crucial information about how to distribute HIVST products effectively, ethically and efficiently. Service delivery models range from clinic-based distribution to workplace and partner-delivered approaches to reach first-time male testers, to community outreach to sex workers and general population "hotspots." These data directly informed supportive policy, notably the 2016 WHO guidelines strongly recommending HIVST as an additional testing approach, and regulatory change through support for WHO prequalification of the first HIVST kit in 2017. In July 2015, only two countries had national HIVST policies and were implementing HIVST. Three years later, 59 countries have policies, actively implemented in 28, with an additional 53 countries reporting policies under development. By end-November 2018 several quality-assured HIVST products had been registered, including two WHO prequalified tests. STAR Initiative countries have drafted regulations governing in vitro diagnostics, including HIVST products. With enabling policies, pre-qualification and regulations in place, donor procurement of kits has increased rapidly, to a forecasted estimate of 16 million HIVST kits procured by 2020. CONCLUSIONS: The STAR Initiative provided a strong foundation to introduce HIVST in LMICs and allow for rapid scale-up based on the wealth of multi-country evidence gathered. Together with sustained coordination and acceleration of market development work, HIVST can help address the testing gap and provide a focused and cost-effective means to expand access to treatment and prevention services.