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Background Cost remains an important barrier to HIV pre-exposure prophlyaxis (PrEP) delivery in Africa. Simplified delivery models that reduce costs without compromising PrEP outcomes are needed. The JiPime-JiPrEP trial tested a model of six-month PrEP dispensing supported with interim HIV self-testing (HIVST) and found non-inferior HIV testing, PrEP refilling, and adherence compared to three-month PrEP dispensing and quarterly clinic visits, the standard-of-care (SOC). We estimated the cost of this novel differentiated PrEP delivery model compared to SOC in Kenya. Methods Using activity-based micro-costing (payer perspective) and time-and-motion observations, we estimated the cost of PrEP delivery (per client-month) in the intervention and SOC between May 2018 to December 2019. Data from budgets and expense reports, published documents, and interviews informed our estimates. We calculated costs over a one-year horizon for: 1) the trial scenario (i.e., costs within the trial), and 2) the Ministy of Health (MOH) scenario (i.e., hypothetical costs at public clinics). Estimates were in 2019 US dollars and excluded research-related costs. Results The mean personnel time attributable to PrEP delivery was 76 minutes per visit and 152 minutes projected over a year in the intervention and 54 minutes per visit and 282 minutes per year in the SOC. In the trial scenario, PrEP delivery cost $17.73 per client-month in the intervention (n=2039 PrEP-months) and $25.50 in the SOC (n=913 PrEP-months). The projected cost of PrEP delivery in the MOH scenario was $11.94 in the intervention and $14.76 in the SOC, with the addition of HIVST kits in the intervention more than offset by personnel savings. In this scenario, personnel (intervention: 55%; SOC: 44%) and medication (intervention: 16%; SOC: 32%) were the primary cost drivers. Including serum creatine testing twice a year in the MOH scenario resulted in a slight increase in the cost of PrEP delivery in the intervention ($12.88 per client-month) versus SOC ($16.17 per client-month). Conclusions Six-month PrEP with interim HIVST demonstrated lower costs than three-month dispensing, with decreased personnel time. Scale-up of PrEP delivery requires efficient use of limited resources; the savings in this model of PrEP delivery could be redirected towards currently unmet medical needs. Clinial trial number NCT03593629|| https://www.clinicaltrials.gov/ with the Clinical Trial Registry (Registration date: 2018-07-20).

Background Effective interventions to reduce HIV incidence in sub-Saharan Africa are urgently needed. Mathematical modelling and the HIV Prevention Trials Network (HPTN) 052 trial results suggest that universal HIV testing combined with immediate antiretroviral treatment (ART) should substantially reduce incidence and may eliminate HIV as a public health problem. We describe the rationale and design of a trial to evaluate this hypothesis. Methods/Design A rigorously-designed trial of universal testing and treatment (UTT) interventions is needed because: i) it is unknown whether these interventions can be delivered to scale with adequate uptake; ii) there are many uncertainties in the models such that the population-level impact of these interventions is unknown; and ii) there are potential adverse effects including sexual risk disinhibition, HIV-related stigma, over-burdening of health systems, poor adherence, toxicity, and drug resistance. In the HPTN 071 (PopART) trial, 21 communities in Zambia and South Africa (total population 1.2 m) will be randomly allocated to three arms. Arm A will receive the full PopART combination HIV prevention package including annual home-based HIV testing, promotion of medical male circumcision for HIV-negative men, and offer of immediate ART for those testing HIV-positive; Arm B will receive the full package except that ART initiation will follow current national guidelines; Arm C will receive standard of care. A Population Cohort of 2,500 adults will be randomly selected in each community and followed for 3 years to measure the primary outcome of HIV incidence. Based on model projections, the trial will be well-powered to detect predicted effects on HIV incidence and secondary outcomes. Discussion Trial results, combined with modelling and cost data, will provide short-term and long-term estimates of cost-effectiveness of UTT interventions. Importantly, the three-arm design will enable assessment of how much could be achieved by optimal delivery of current policies and the costs and benefits of extending this to UTT. Trial registration ClinicalTrials.gov NCT01900977 .

With the increase in people living with HIV in sub-Saharan Africa and expanding eligibility criteria for antiretroviral therapy (ART), there is intense interest in the use of novel delivery models that allow understaffed health systems to successfully deal with an increasing demand for antiretroviral drugs (ARVs). This pragmatic randomized controlled trial in Dar es Salaam, Tanzania, evaluated a novel model of ARV community delivery: lay health workers (home-based carers [HBCs]) deliver ARVs to the homes of patients who are clinically stable on ART, while nurses and physicians deliver standard facility-based care for patients who are clinically unstable. Specifically, the trial aimed to assess whether the ARV community delivery model performed at least equally well in averting virological failure as the standard of care (facility-based care for all ART patients). The study took place from March 1, 2016, to October 27, 2017. All (48) healthcare facilities in Dar es Salaam that provided ART and had an affiliated team of public-sector HBCs were randomized 1:1 to either (i) ARV community delivery (intervention) or (ii) the standard of care (control). Our prespecified primary endpoint was the proportion of adult non-pregnant ART patients with virological failure at the end of the study period. The prespecified margin of non-inferiority was a risk ratio (RR) of 1.45. The mean follow-up period was 326 days. We obtained intent-to-treat (ITT) RRs using a log-binomial model adjusting standard errors for clustering at the level of the healthcare facility. A total of 2,172 patients were enrolled at intervention (1,163 patients) and control (1,009 patients) facilities. Of the 1,163 patients in the intervention arm, 516 (44.4%) were both clinically stable on ART and opted to receive ARVs in their homes or at another meeting point of their choosing in the community. At the end of the study period, 10.9% (95/872) of patients in the control arm and 9.7% (91/943) in the intervention arm were failing virologically. The ITT RR for virological failure demonstrated non-inferiority of the ARV community delivery model (RR 0.89 [1-sided 95% CI 0.00-1.18]). We observed no significant difference between study arms in self-reported patient healthcare expenditures over the last 6 months before study exit. Of those who received ARVs in the community, 97.2% (95% CI 94.7%-98.7%) reported being either \"satisfied\" or \"very satisfied\" with the program. Other than loss to follow-up (18.9% in the intervention and 13.6% in the control arm), the main limitation of this trial was that substantial decongestion of healthcare facilities was not achieved, thus making the logic for our preregistered ITT approach (which includes those ineligible to receive ARVs at home in the intervention sample) less compelling. In this study, an ARV community delivery model performed at least as well as the standard of care regarding the critical health indicator of virological failure. The intervention did not significantly reduce patient healthcare expenditures, but satisfaction with the program was high and it is likely to save patients time. Policy-makers should consider piloting, evaluating, and scaling more ambitious ARV community delivery programs that can reach higher proportions of ART patients. ClinicalTrials.gov NCT02711293.

We used results from an optimization randomized controlled trial which tested five behavioral intervention components to support HIV antiretroviral adherence/HIV viral suppression, grounded in the multiphase optimization strategy and using a fractional factorial design to identify intervention components with cost-effectiveness sufficiently favorable for scalability. Results were incorporated into a validated HIV computer simulation to simulate longer-term effects of combinations of components on health and costs. We simulated the 32 corresponding long-term trajectories for viral load suppression, health related quality of life (HRQoL), and costs. The components were designed to be culturally and structurally salient. They were: motivational interviewing counseling sessions (MI), pre-adherence skill building (SB), peer mentorship (PM), focused support groups (SG), and patient navigation (short version [NS], long version [NL]. All participants also received health education on HIV treatment. We examined four scenarios: one-time intervention with and without discounting and continuous interventions with and without discounting. In all four scenarios, interventions that comprise or include SB and NL (and including health education) were cost effective (< $100,000/quality-adjusted life year). Further, with consideration of HRQoL impact, maximal intervention became cost-effective enough to be scalable. Thus, a fractional factorial experiment coupled with cost-effectiveness analysis is a promising approach to optimize multi-component interventions for scalability. The present study can guide service planning efforts for HIV care settings and health departments.

Background. Drug users (DUs), a population that accounts for some of the fastest-growing human immunodeficiency virus (HIV) epidemics globally, lag behind other populations with regard to HIV-related outcomes. We evaluated the role of voucher incentives on linkage and retention in care among DUs in India. Methods. In this randomized clinical trial, 120 DUs who were aged ≥18 years, HIV-infected, antiretroviral therapy (ART) naive, and ART eligible and who reported drug use in the prior month were randomized to incentive (INC) or control (CTL) conditions for 12 months. Participants randomized to the INC arm received incentives (redeemable for food/household goods) ranging in value from USD4 to USD8 for achieving prespecified targets (eg, ART initiation, visits to ART center). Subjects in the CTL group could win vouchers in prize-bowl drawings, but HIV care behaviors were not incentivized. The primary endpoint was time to ART initiation. Results. Sixty participants each were randomized to the INC and CTL arms between December 2009 and September 2010. Participants in the INC arm were more likely to visit the government ART center (49 vs 33; P = .002); 27 participants in the INC and 16 participants in the CTL arm initiated ART (P= .04; hazard ratio for ART = 2.33 [95% confidence interval, 1.15–4.73]). Participants in the INC arm also had significantly more visits to the ART center (median number of visits, 8 vs 3.5; P = .005). However, no difference in viral suppression was observed. Conclusions. Modest voucher incentives improved linkage to and retention in HIV care, but did not significantly impact viral suppression among DUs in India, a disenfranchised and difficult-to-treat population. Clinical Trials Registration. NCT01031745.

Understanding the costs associated with health care delivery strategies is essential for planning. There are few data on health service resources used by patients and their associated costs within antiretroviral (ART) programmes in Africa. The study was nested within a large trial, which evaluated screening for cryptococcal meningitis and tuberculosis and a short initial period of home-based adherence support for patients initiating ART with advanced HIV disease in Tanzania and Zambia. The economic evaluation was done in Tanzania alone. We estimated costs of providing routine ART services from the health service provider's perspective using a micro-costing approach. Incremental costs for the different novel components of service delivery were also estimated. All costs were converted into US dollars (US$) and based on 2012 prices. Of 870 individuals enrolled in Tanzania, 434 were enrolled in the intervention arm and 436 in the standard care/control arm. Overall, the median (IQR) age and CD4 cell count at enrolment were 38 [31, 44] years and 52 [20, 89] cells/mm3, respectively. The mean per patient costs over the first three months and over a one year period of follow up following ART initiation in the standard care arm were US$ 107 (95%CI 101-112) and US$ 265 (95%CI 254-275) respectively. ART drugs, clinic visits and hospital admission constituted 50%, 19%, and 19% of the total cost per patient year, while diagnostic tests and non-ART drugs (co-trimoxazole) accounted for 10% and 2% of total per patient year costs. The incremental costs of the intervention to the health service over the first three months was US$ 59 (p<0.001; 95%CI 52-67) and over a one year period was US$ 67(p<0.001; 95%CI 50-83). This is equivalent to an increase of 55% (95%CI 51%-59%) in the mean cost of care over the first three months, and 25% (95%CI 20%-30%) increase over one year of follow up.

Introduction HIV self‐testing (HIVST) in outpatient departments (OPD) is a promising strategy for HIV testing in Malawi, given high OPD patient volumes and substantial wait times. To evaluate the relative cost and expected impact of facility‐based HIVST (FB‐HIVST) at OPDs in Malawi for increasing HIV status awareness, we conducted an economic evaluation of an HIVST cluster‐randomized controlled trial. Methods A cluster‐randomized trial was conducted at 15 sites in Malawi from September 2017 to February 2018 with three arms: 1) Standard provider‐initiated‐testing‐and‐counselling (PITC); 2) Optimized PITC (additional provider training and job‐aids) and 3) FB‐HIVST (HIVST demonstration, distribution and kit use in OPD, private kit interpretation and optional HIV counselling). The total production cost per newly identified positive and per person newly initiated on ART were calculated by study arm. These were calculated as the total cost of testing everyone divided by the number of newly identified positives; and the total cost of testing everyone divided by the number of those initiated on ART. Cost‐outcomes were calculated under three cost scenarios: (1) full study costs, (2) routine implementation costs and (3) routine implementation + reduced cost for HIVST kits. Results The average cost per person newly diagnosed in the full study cost scenario was$101, $ 156 and$189, and cost per person initiated on ART was $ 121,$156 and $ 279 for Standard PITC, Optimized PITC and FB‐HIVST respectively. In the routine implementation cost scenario, the average cost per person newly diagnosed was reduced to$83, and $ 93, and cost per person initiated on ART to$83, and $ 137 for Optimized PITC and FB‐HIVST respectively. In the negotiated HIVST cost scenario, the average cost per person newly diagnosed was reduced to$55 and cost per person newly initiated on ART reduced to $ 81 in the FB‐HIVST arm. Conclusions While the cost per new ART initiation through FB‐HIVST was higher than Standard PITC, FB‐HIVST could become cost‐saving compared to PITC if the cost of kits is reduced or if treatment linkage rate were increased in the FB‐HIVST arm. For high volume OPDs, HIVST may increase facility capacity and increase the number of newly diagnosed positives.

Background Many HIV-positive patients do not appropriately adhere to their antiretroviral medication (ART). This leads to higher viral loads and greater probability of HIV transmission. Present bias—a tendency to give in to short-term temptations at the expense of long-term outcomes—is a potential driver of low adherence. In this study we test a novel intervention rooted in behavioral economics that is designed to overcome present bias and increase ART adherence. Methods/design We will enroll 330 HIV-positive patients at Mildmay Hospital in Kampala, Uganda, into a 2-year randomized controlled trial. Participants will be randomized to one of three groups. The first intervention group (T1, n  = 110) will be eligible for small lottery prizes based on timely clinic visits and demonstration of viral suppression. Group 2 (T2, n  = 110) will be eligible for the same lottery prizes conditional on high adherence measured by a medication event management system (MEMS) cap. The control group ( n  = 110) will receive the usual standard of care. Adherence will be measured continuously throughout the intervention period and for 12 months post-intervention to evaluate effect persistence. Surveys will be conducted at baseline and then every 6 months. Viral loads will be measured annually. Primary outcomes are whether the viral load is detectable and MEMS-measured adherence. Secondary outcomes are the log-transformed viral load as a continuous measure and a binary measure for whether the person took at least 90% of their ART pills. Discussion Our study is one of the first to investigate the effectiveness of lottery incentives for improving ART adherence, and in addition, it compares the relative efficacy of using electronically measured adherence versus viral load to determine lottery eligibility. MEMS caps are relatively costly, whereas viral load testing is now part of routine clinical care in Uganda. BEST will test whether directly incentivizing viral suppression (which can be implemented using readily available clinic data) is as effective as incentivizing electronically measured adherence. Cost-effectiveness analyses of the two implementation modes will also be performed. Trial registration ClinicalTrials.gov, NCT03494777 . Registered on 11 April 2018.

Background Sub-Saharan Africa is the world region with the greatest number of people eligible to receive antiretroviral treatment (ART). Less frequent dispensing of ART and community-based ART-delivery models are potential strategies to reduce the load on overburdened healthcare facilities and reduce the barriers for patients to access treatment. However, no large-scale trials have been conducted investigating patient outcomes or evaluating the cost-effectiveness of extended ART-dispensing intervals within community ART-delivery models. This trial will assess the clinical effectiveness, cost-effectiveness and acceptability of providing ART refills on a 3 vs. a 6-monthly basis within community ART-refill groups (CARGs) for stable patients in Zimbabwe. Methods In this pragmatic, three-arm, parallel, unblinded, cluster-randomized non-inferiority trial, 30 clusters (healthcare facilities and associated CARGs) are allocated using stratified randomization in a 1:1:1 ratio to either (1) ART refills supplied 3-monthly from the health facility (control arm), (2) ART refills supplied 3-monthly within CARGs, or (3) ART refills supplied 6-monthly within CARGs. A CARG consists of 6–12 stable patients who meet in the community to receive ART refills and who provide support to one another. Stable adult ART patients with a baseline viral load < 1000 copies/ml will be invited to participate (1920 participants per arm). The primary outcome is the proportion of participants alive and retained in care 12 months after enrollment. Secondary outcomes (measured at 12 and 24 months) are the proportions achieving virological suppression, average provider cost per participant, provider cost per participant retained, cost per participant retained with virological suppression, and average patient-level costs to access treatment. Qualitative research will assess the acceptability of extended ART-dispensing intervals within CARGs to both providers and patients, and indicators of potential facility-level decongestion due to the interventions will be assessed. Discussion Cost-effective health system models that sustain high levels of patient retention are urgently needed to accommodate the large numbers of stable ART patients in sub-Saharan Africa. This will be the first trial to evaluate extended ART-dispensing intervals within a community-based ART distribution model, and results are intended to inform national and regional policy regarding their potential benefits to both the healthcare system and patients. Trial registration ClinicalTrials.gov, ID: NCT03238846 . Registered on 27 July 2017.

Despite funding constraints for treatment programmes in Africa, the costs and economic consequences of routine laboratory monitoring for efficacy and toxicity of antiretroviral therapy (ART) have rarely been evaluated. Cost-effectiveness analysis was conducted in the DART trial (ISRCTN13968779). Adults in Uganda/Zimbabwe starting ART were randomised to clinically-driven monitoring (CDM) or laboratory and clinical monitoring (LCM); individual patient data on healthcare resource utilisation and outcomes were valued with primary economic costs and utilities. Total costs of first/second-line ART, routine 12-weekly CD4 and biochemistry/haematology tests, additional diagnostic investigations, clinic visits, concomitant medications and hospitalisations were considered from the public healthcare sector perspective. A Markov model was used to extrapolate costs and benefits 20 years beyond the trial. 3316 (1660LCM;1656CDM) symptomatic, immunosuppressed ART-naive adults (median (IQR) age 37 (32,42); CD4 86 (31,139) cells/mm(3)) were followed for median 4.9 years. LCM had a mean 0.112 year (41 days) survival benefit at an additional mean cost of $765 [95%CI:685,845], translating into an adjusted incremental cost of $7386 [3277,dominated] per life-year gained and $7793 [4442,39179] per quality-adjusted life year gained. Routine toxicity tests were prominent cost-drivers and had no benefit. With 12-weekly CD4 monitoring from year 2 on ART, low-cost second-line ART, but without toxicity monitoring, CD4 test costs need to fall below $3.78 to become cost-effective (<3xper-capita GDP, following WHO benchmarks). CD4 monitoring at current costs as undertaken in DART was not cost-effective in the long-term. There is no rationale for routine toxicity monitoring, which did not affect outcomes and was costly. Even though beneficial, there is little justification for routine 12-weekly CD4 monitoring of ART at current test costs in low-income African countries. CD4 monitoring, restricted to the second year on ART onwards, could be cost-effective with lower cost second-line therapy and development of a cheaper, ideally point-of-care, CD4 test.