The effects of revised peer-counselor support on the PMTCT cascade of care: results from a cluster-randomized trial in Kenya (the EMMA study).

BACKGROUND: This study evaluated the effect of revisions to existing peer-counselor services, called Mentor Mothers (MM), at maternal and child health clinics on medication adherence for women living with HIV (WLWH) in Kenya and on early infant HIV testing. METHODS: The Enhanced Mentor Mother Program study was a 12-site, two-arm cluster-randomized trial enrolling pregnant WLWH from March 2017 to June 2018 (with data collection through September 2020). Six clinics were randomized to continued MM-supported standard care (SC). Six clinics were randomized to the intervention arm (INT = SC plus revised MM services to include more one-on-one interactions). Primary outcomes for mothers were defined as: (PO1) the proportion of days covered (PDC) with antiretroviral therapy (ART) ≥ 0.90 during the last 24-weeks of pregnancy; and (PO2) ≥ 0.90 PDC during the first 24-weeks postpartum. Secondary outcomes were infant HIV testing according to national guidelines (at 6, 24, and 48 weeks). Crude and adjusted risk differences between study arms are reported. RESULTS: We enrolled 363 pregnant WLHV. After excluding known transfers and subjects with incomplete data extraction, data were analyzed for 309 WLWH (151 SC, 158 INT). A small share achieved high PDC during the prenatal and postnatal periods (0.33 SC/0.24 INT achieved PO1; 0.30 SC/0.31 INT achieved PO2; crude or adjusted risk differences were not statistically significant). In addition, ~ 75% in both study arms completed viral load testing during year two after enrollment, with > 90% suppressed in both arms. For infants, ≥ 90% in both arms had at least one HIV test through study follow up (76 weeks) but testing on schedule according to PMTCT guidelines was uncommon. CONCLUSIONS: While national guidelines in Kenya recommended that all HIV-infected pregnant women take a daily antiretroviral regimen for life following a HIV diagnosis, results presented here indicate that a minor share achieved high medication coverage during the prenatal and postnatal periods analyzed. In addition, adjustments to Mentor-Mother services showed no improvement in study outcomes. The lack of effect for this behavioral intervention is relatively consistent with the existing literature to improve mother-infant outcomes along the PMTCT care cascade. CLINICAL TRIAL NUMBER: NCT02848235. Date of first trial registration 28/07/2016.

Cost-effectiveness of single-dose AmBisome pre-emptive treatment for the prevention of cryptococcal meningitis in African low and middle-income countries.

Cryptococcal antigen (CrAg) screening is recommended for patients with advanced HIV to reduce AIDS-related mortality. For asymptomatic CrAg-positive persons, fluconazole pre-emptive therapy is standard, despite a ∼25% failure rate. Single-dose liposomal amphotericin B (AmBisome) is non-inferior to standard treatment for cryptococcal meningitis. We evaluate the threshold of efficacy necessary for AmBisome + fluconazole to be cost-effective as pre-emptive therapy for CrAg-positive persons.We created a decision analytic model to evaluate CrAg screening and treatment in HIV-infected persons with CD4 < 100 cells/µL. Costs were estimated for screening, pre-emptive therapy, and hospitalization for an example low-income country (Uganda) and middle-income country (South Africa). We used a discounted price range of AmBisome® at ${\$}$16.25 to ${\$}$40 per 50 mg vial for both Uganda and South Africa. We estimated AmBisome efficacy from 75 to 95%. Parameter assumptions were based on prospective CrAg screening studies and clinical trials in Africa. Disability adjusted life years (DALYs) were calculated using the age-specific life expectancy in Uganda, per WHO Global Health Observatory data. We modeled the theoretical efficacy of adjunctive AmBisome to determine cost per DALY averted.In South Africa, at ${\$}$16.25 per vial cost and a minimum efficacy of 85%, adjunctive AmBisome is cost-saving compared to fluconazole monotherapy. Compared to fluconazole pre-emptive therapy in Uganda, AmBisome + fluconazole would cost ${\$}$475, ${\$}$220, or ${\$}$136 per DALY averted if meningitis-free survival efficacy was 80, 85, or 90% at ${\$}$24 per vial cost.Investing in AmBisome may be cost-effective in low-income settings compared to using fluconazole pre-emptive therapy alone, if efficacy is 85% or greater. AmBisome pre-emptive therapy appears more cost-efficient in middle-income settings where hospitalization costs for meningitis, and GDP per capita are higher. LAY SUMMARY: We evaluate the efficacy necessary for AmBisome + fluconazole to be cost-effective to prevent cryptococcal meningitis. We found that if AmBisome pre-emptive therapy has an efficacy of 85% or greater, it is likely to be cost-effective in low-income settings.

Simplified clinical algorithm for identifying patients eligible for same-day HIV treatment initiation (SLATE): Results from an individually randomized trial in South Africa and Kenya.

BACKGROUND: The World Health Organization recommends "same-day" initiation of antiretroviral therapy (ART) for HIV patients who are eligible and ready. Identifying efficient, safe, and feasible procedures for determining same-day eligibility and readiness is now a priority. The Simplified Algorithm for Treatment Eligibility (SLATE) study evaluated a clinical algorithm that allows healthcare workers to determine eligibility for same-day treatment and to initiate ART at the patient's first clinic visit. METHODS AND FINDINGS: SLATE was an individually randomized trial at three outpatient clinics in urban settlements in Johannesburg, South Africa and three hospital clinics in western Kenya. Adult, nonpregnant, HIV-positive, ambulatory patients presenting for any HIV care, including HIV testing, but not yet on ART were enrolled and randomized to the SLATE algorithm arm or standard care. The SLATE algorithm used four screening tools-a symptom self-report, medical history questionnaire, physical examination, and readiness assessment-to ascertain eligibility for same-day initiation or refer for further care. Follow-up was by record review, and analysis was conducted by country. We report primary outcomes of 1) ART initiation ≤28 days and 2) initiation ≤28 days and retention in care ≤8 months of enrollment. From March 7, 2017 to April 17, 2018, we enrolled 600 patients (median [IQR] age 34 [29-40] and CD4 count 286 [128-490]; 63% female) in South Africa and 477 patients in Kenya (median [IQR] age 35 [29-43] and CD4 count 283 [117-541]; 58% female). In the intervention arm, 78% of patients initiated ≤28 days in South Africa, compared to 68% in the standard arm (risk difference [RD] [95% confidence interval (CI)] 10% [3%-17%]); in Kenya, 94% of intervention-arm patients initiated ≤28 days compared to 89% in the standard arm (6% [0.5%-11%]). By 8 months in South Africa, 161/298 (54%) intervention-arm patients had initiated and were retained, compared to 146/302 (48%) in the standard arm (6% [(2% to 14%]). By 8 months in Kenya, the corresponding retention outcomes were identical in both arms (137/240 [57%] of intervention-arm patients and 136/237 [57%] of standard-arm patients). Limitations of the trial included limited geographic representativeness, exclusion of patients too ill to participate, missing viral load data, greater study fidelity to the algorithm than might be achieved in standard care, and secular changes in standard care over the course of the study. CONCLUSIONS: In South Africa, the SLATE algorithm increased uptake of ART within 28 days by 10% and showed a numerical increase (6%) in retention at 8 months. In Kenya, the algorithm increased uptake of ART within 28 days by 6% but found no difference in retention at 8 months. Eight-month retention was poor in both arms and both countries. These results suggest that a simple structured algorithm for same-day treatment initiation procedures is feasible and can increase and accelerate ART uptake but that early retention on treatment remains problematic. TRIAL REGISTRATION: Clinicaltrials.gov NCT02891135, registered September 1, 2016. First participant enrolled March 6, 2017 in South Africa and July 13, 2017 in Kenya.

Designing an optimal HIV programme for South Africa: Does the optimal package change when diminishing returns are considered?

BACKGROUND: South Africa has a large domestically funded HIV programme with highly saturated coverage levels for most prevention and treatment interventions. To further optimise its allocative efficiency, we designed a novel optimisation method and examined whether the optimal package of interventions changes when interaction and non-linear scale-up effects are incorporated into cost-effectiveness analysis. METHODS: The conventional league table method in cost-effectiveness analysis relies on the assumption of independence between interventions. We added methodology that allowed the simultaneous consideration of a large number of HIV interventions and their potentially diminishing marginal returns to scale. We analysed the incremental cost effectiveness ratio (ICER) of 16 HIV interventions based on a well-calibrated epidemiological model that accounted for interaction and non-linear scale-up effects, a custom cost model, and an optimisation routine that iteratively added the most cost-effective intervention onto a rolling baseline before evaluating all remaining options. We compared our results with those based on a league table. RESULTS: The rank order of interventions did not differ substantially between the two methods- in each, increasing condom availability and male medical circumcision were found to be most cost-effective, followed by anti-retroviral therapy at current guidelines. However, interventions were less cost-effective throughout when evaluated under the optimisation method, indicating substantial diminishing marginal returns, with ICERs being on average 437% higher under our optimisation routine. CONCLUSIONS: Conventional league tables may exaggerate the cost-effectiveness of interventions when programmes are implemented at scale. Accounting for interaction and non-linear scale-up effects provides more realistic estimates in highly saturated real-world settings.

Accelerating the Uptake and Timing of Antiretroviral Therapy Initiation in Sub-Saharan Africa: An Operations Research Agenda.

Sydney Rosen and colleagues describe an operations research agenda to accelerating uptake of HIV treatment initiation.

A framework for evaluating the costs of malaria elimination interventions: an application to reactive case detection in Southern Province of Zambia, 2014.

BACKGROUND: This paper summarizes a framework for evaluating the costs of malaria elimination interventions and applies this approach to one key component of the elimination strategy-reactive case detection (RCD)-implemented through 173 health facilities across 10 districts in Southern Province of Zambia during 2014. METHODS: The primary unit of analysis is the health facility catchment area (HFCA). A five-step approach was followed to estimate implementation costs: organize preliminary information; estimate basic unit costs; estimate activity unit costs; estimate and organize final unit cost database; and create the final costing database (one row of data per HFCA). By working through a specific application, the overall logic of the analysis and details of each step are presented. An electronic annex also provides all details of the analysis. Because population varies substantially across HFCAs, all results are reported per 1000 population in HFCAs. RESULTS: During 2014, 38.9 households per HFCA were visited for RCD services; 166.8 individuals were tested and 32.3 tested positive and were treated. The mean annual cost per HFCA was $1177 (median = $923, IQR $651-$1417). Variation in costs was driven by the number of CHWs and passive cases detected. CHW-related costs and data review meetings accounted for the largest share of costs. Rapid diagnostic tests and drugs accounted for less than 10 % of total costs. CONCLUSIONS: The framework presented here follows standard methods in applied costing of public health interventions (combining ingredients- and activity-based costing approaches into one final cost analysis). Through an application to a specific programme implemented in Zambia in 2014, the details of how to apply such methods to an actual programme are presented. Such details are not typically presented in existing costing analyses but are required for applied analysts working with national malaria control programmes and other organizations to complete such analyses as part of routine programme implementation. Obtaining data and information for implementing the approach remains complicated, in part because analysts from one organization may not have easy access to information from another organization. This basic approach is transparent and easily applied to other malaria elimination interventions being implemented in sub-Saharan Africa and elsewhere.

Delays, interruptions, and losses from prevention of mother-to-child transmission of HIV services during antenatal care in Johannesburg, South Africa: a cohort analysis.

BACKGROUND: Between 2010-2013, South Africa implemented WHO 'Option A' for prevention of mother to child transmission (PMTCT), where all HIV-infected pregnant women (from 14 weeks gestation) received zidovudine (AZT) as ARV prophylaxis and initiated CD4 testing at their first antenatal care (ANC) visit. After returning for a second visit to collect CD4 results, women with CD4 counts ≤ 350 were referred to the ART clinic and fast-tracked for initiation on lifelong ART while continuing to visit the ANC clinic every four weeks. Women with CD4 counts >350 were dispensed daily AZT prophylaxis at monthly follow up visits (every 4 weeks). The primary objective of this study was to evaluate adherence of HIV-infected pregnant women to recommended PMTCT services at and after their first antenatal care (ANC) visit. METHODS: We conducted an observational cohort study from August 2012 to February 2013 at two primary health care clinics in Johannesburg, South Africa using routinely collected clinic data from first ANC visit for up to 60 days. RESULTS: Of the 158 patients newly diagnosed with HIV at their first ANC visit, records indicated that 139 women initiated CD4 testing during their first ANC visit. 52 patients (33% of 158) did not return again to the clinic within 60 days. Of the 118 (84% of 139) women with known gestational age > 13 weeks and known Hb ≥ 8 g/dl who should have received a 4-week supply of daily AZT at first ANC visit, 81 women (69% of 118) had a record of AZT being dispensed. Among the 139 women with CD4 results, 72 (52%) were eligible for lifelong ART (CD4 count ≤350); however, only 2 initiated ART within 30 days. CONCLUSIONS: Loss to initiation of both single and triple ARV therapy, loss to follow-up, and treatment interruptions were common during ANC care for pregnant women with HIV after their first ANC visit.

Retention in care, resource utilization, and costs for adults receiving antiretroviral therapy in Zambia: a retrospective cohort study.

BACKGROUND: Of the estimated 800,000 adults living with HIV in Zambia in 2011, roughly half were receiving antiretroviral therapy (ART). As treatment scale up continues, information on the care provided to patients after initiating ART can help guide decision-making. We estimated retention in care, the quantity of resources utilized, and costs for a retrospective cohort of adults initiating ART under routine clinical conditions in Zambia. METHODS: Data on resource utilization (antiretroviral [ARV] and non-ARV drugs, laboratory tests, outpatient clinic visits, and fixed resources) and retention in care were extracted from medical records for 846 patients who initiated ART at ≥15 years of age at six treatment sites between July 2007 and October 2008. Unit costs were estimated from the provider's perspective using site- and country-level data and are reported in 2011 USD. RESULTS: Patients initiated ART at a median CD4 cell count of 145 cells/µL. Fifty-nine percent of patients initiated on a tenofovir-containing regimen, ranging from 15% to 86% depending on site. One year after ART initiation, 75% of patients were retained in care. The average cost per patient retained in care one year after ART initiation was $243 (95% CI, $194-$293), ranging from $184 (95% CI, $172-$195) to $304 (95% CI, $290-$319) depending on site. Patients retained in care one year after ART initiation received, on average, 11.4 months' worth of ARV drugs, 1.5 CD4 tests, 1.3 blood chemistry tests, 1.4 full blood count tests, and 6.5 clinic visits with a doctor or clinical officer. At all sites, ARV drugs were the largest cost component, ranging from 38% to 84% of total costs, depending on site. CONCLUSIONS: Patients initiate ART late in the course of disease progression and a large proportion drop out of care after initiation. The quantity of resources utilized and costs vary widely by site, and patients utilize a different mix of resources under routine clinical conditions than if they were receiving fully guideline-concordant care. Improving retention in care and guideline concordance, including increasing the use of tenofovir in first-line ART regimens, may lead to increases in overall treatment costs.

Exploring impacts of multi-year, community-based care programs for orphans and vulnerable children: a case study from Kenya.

The Community-Based Care for Orphans and Vulnerable Children (CBCO) program operated in Kenya during 2006-2010. In Eastern Province, the program provided support to approximately 3000 orphans and vulnerable children (OVC) living in 1500 households. A primary focus of the program was to support savings and loan associations composed of OVC caregivers (typically elderly women) to improve household and OVC welfare. Cross-sectional data were collected in 2011 from 1500 randomly selected households from 3 populations: program participants (CBCO group, n=500), households in the same villages as program participants but not in the program (the local-community-group = Group L, n=300), and households living in nearby villages where the program did not operate (the adjacent-community-group, Group A, n=700). Primary welfare outcomes evaluated are household food security, as measured by the Household Food Insecurity Access instrument, and OVC educational attainment. We compared outcomes between the CBCO and the subset of Group L not meeting program eligibility criteria (L-N) to investigate disparities within local communities. We compared outcomes between the CBCO group and the subset of Group A meeting eligibility criteria (A-E) to consider program impact. We compared outcomes between households not eligible for the program in the local and adjacent community groups (L-N and A-N) to consider if the adjacent communities are similar to the local communities. In May-June 2011, at the end of the OVC program, the majority of CBCO households continued to be severely food insecure, with rates similar to other households living in nearby communities. Participation rates in primary school are high, reflecting free primary education. Among the 18-22 year olds who were "children" during the program years, relatively few children completed secondary school across all study groups. Although the CBCO program likely provided useful services and benefits to program participants, disparities continued to exist in food security and educational outcomes between program participants and their non-OVC peers in the local community. Outcomes for CBCO households were similar to those observed for OVC households in adjacent communities.

Calculating disability-adjusted-life-years lost (DALYs) in discrete-time.

Disability-adjusted-life-years lost (DALYs) is a common outcome metric for cost-effectiveness analyses, and the equations used for such calculations have been presented previously by Fox-Rushby and Hanson (see, e.g., "Health Policy and Planning 16:326-331, 2001"). While the equations are clear, the logic behind them is opaque at best for a large share of public health practitioners and students. The objective of this paper is to show how to calculate DALYs using a discrete time formulation that is easy to teach to students and public health practitioners, is easy to apply for those with basic discounting skills, and is consistent with the discounting methods typically included on the costing side of cost-effectiveness analysis. A continuous-time adjustment factor is derived that can be used to ensure exact consistency between the continuous and discrete time approaches, but this level of precision is typically unnecessary for cost-effectiveness analyses. To illustrate the approach, both a new, simple example and the same example presented in Fox-Rushby and Hanson are used throughout the paper.

Getting resources to those who need them: the evidence we need to budget for underserved populations in sub-Saharan Africa.

INTRODUCTION: In recent years, many countries have adopted evidence-based budgeting (EBB) to encourage the best use of limited and decreasing HIV resources. The lack of data and evidence for hard to reach, marginalized and vulnerable populations could cause EBB to further disadvantage those who are already underserved and who carry a disproportionate HIV burden (USDB). We outline the critical data required to use EBB to support USDB people in the context of the generalized epidemics of sub-Saharan Africa (SSA). DISCUSSION: To be considered in an EBB cycle, an intervention needs at a minimum to have an estimate of a) the average cost, typically per recipient of the intervention; b) the effectiveness of the intervention and c) the size of the intervention target population. The methods commonly used for general populations are not sufficient for generating valid estimates for USDB populations. USDB populations may require additional resources to learn about, access, and/or successfully participate in an intervention, increasing the cost per recipient. USDB populations may experience different health outcomes and/or other benefits than in general populations, influencing the effectiveness of the interventions. Finally, USDB population size estimation is critical for accurate programming but is difficult to obtain with almost no national estimates for countries in SSA. We explain these limitations and make recommendations for addressing them. CONCLUSIONS: EBB is a strong tool to achieve efficient allocation of resources, but in SSA the evidence necessary for USDB populations may be lacking. Rather than excluding USDB populations from the budgeting process, more should be invested in understanding the needs of these populations.

Fast-track treatment initiation counselling in South Africa: A cost-outcomes analysis.

INTRODUCTION: In 2016, under its new National Adherence Guidelines (AGL), South Africa formalized an existing model of fast-track HIV treatment initiation counselling (FTIC). Rollout of the AGL included an evaluation study at 24 clinics, with staggered AGL implementation. Using routinely collected data extracted as part of the evaluation study, we estimated and compared the costs of HIV care and treatment from the provider's perspective at the 12 clinics implementing the new, formalized model (AGL-FTIC) to costs at the 12 clinics continuing to implement some earlier, less formalized, model that likely varied across clinics (denoted here as early-FTIC). METHODS: This was a cost-outcome analysis using standard methods and a composite outcome defined as initiated antiretroviral therapy (ART) within 30 days of treatment eligibility and retained in care at 9 months. Using patient-level, bottom-up resource-utilization data and local unit costs, we estimated patient-level costs of care and treatment in 2017 U.S. dollars over the 9-month evaluation follow-up period for the two models of care. Resource use and costs, disaggregated by antiretroviral medications, laboratory tests, and clinic visits, are reported by model of care and stratified by the composite outcome. RESULTS: A total of 350/343 patients in the early-FTIC/AGL-FTIC models of care are included in this analysis. Mean/median costs were similar for both models of care ($135/$153 for early-FTIC, $130/$151 for AGL-FTIC). For the subset achieving the composite outcome, resource use and therefore mean/median costs were similar but slightly higher, reflecting care consistent with treatment guidelines ($163/$166 for early-FTIC, $168/$170 for AGL-FTIC). Not surprisingly, costs for patients not achieving the composite outcome were substantially less, mainly because they only had two or fewer follow-up visits and, therefore, received substantially less ART than patients who achieved the composite outcome. CONCLUSION: The 2016 adherence guidelines clarified expectations for the content and timing of adherence counseling sessions in relation to ART initiation. Because clinics were already initiating patients on ART quickly by 2016, little room existed for the new model of fast-track initiation counseling to reduce the number of pre-ART clinic visits at the study sites and therefore to reduce costs of care and treatment. TRIAL REGISTRATION: Clinical Trial Number: NCT02536768.

Cost-effectiveness of cryptococcal antigen screening at CD4 counts of 101-200 cells/µL in Botswana.

Background: Cryptococcal antigen (CrAg) screening in individuals with advanced HIV reduces cryptococcal meningitis (CM) cases and deaths. The World Health Organization recently recommended increasing screening thresholds from CD4 ≤100 cells/µL to ≤200 cells/µL. CrAg screening at CD4 ≤100 cells/µL is cost-effective; however, the cost-effectiveness of screening patients with CD4 101-200 cells/µL requires evaluation. Methods: Using a decision analytic model with Botswana-specific cost and clinical estimates, we evaluated CrAg screening and treatment among individuals with CD4 counts of 101-200 cells/µL. We estimated the number of CM cases and deaths nationally and treatment costs without screening. For screening we modeled the number of CrAg tests performed, number of CrAg-positive patients identified, proportion started on pre-emptive fluconazole, CM cases and deaths. Screening and treatment costs were estimated and cost per death averted or disability-adjusted life year (DALY) saved compared with no screening. Results: Without screening, we estimated 142 CM cases and 85 deaths annually among individuals with CD4 101-200 cells/µL, with treatment costs of $368,982. With CrAg screening, an estimated 33,036 CrAg tests are performed, and 48 deaths avoided (1,017 DALYs saved).  While CrAg screening costs an additional $155,601, overall treatment costs fall by $39,600 (preemptive and hospital-based CM treatment), yielding a net increase of $116,001. Compared to no screening, high coverage of CrAg screening and pre-emptive treatment for CrAg-positive individuals in this population avoids one death for $2440 and $114 per DALY saved. In sensitivity analyses assuming a higher proportion of antiretroviral therapy (ART)-naïve patients (75% versus 15%), cost per death averted was $1472; $69 per DALY saved. Conclusions: CrAg screening for individuals with CD4 101-200 cells/µL was estimated to have a modest impact, involve additional costs, and be less cost-effective than screening populations with CD4 counts ≤100 cells/µL. Additional CrAg screening costs must be considered against other health system priorities.

Lost opportunities to complete CD4+ lymphocyte testing among patients who tested positive for HIV in South Africa.

OBJECTIVE: To estimate rates of completion of CD4+ lymphocyte testing (CD4 testing) within 12 weeks of testing positive for human immunodeficiency virus (HIV) at a large HIV/AIDS clinic in South Africa, and to identify clinical and demographic predictors for completion. METHODS: In our study, CD4 testing was considered complete once a patient had retrieved the test results. To determine the rate of CD4 testing completion, we reviewed the records of all clinic patients who tested positive for HIV between January 2008 and February 2009. We identified predictors for completion through multivariate logistic regression. FINDINGS: Of the 416 patients who tested positive for HIV, 84.6% initiated CD4 testing within the study timeframe. Of these patients, 54.3% were immediately eligible for antiretroviral therapy (ART) because of a CD4 cell count ≤ 200/µl, but only 51.3% of the patients in this category completed CD4 testing within 12 weeks of HIV testing. Among those not immediately eligible for ART (CD4 cells > 200/µl), only 14.9% completed CD4 testing within 12 weeks. Overall, of HIV+ patients who initiated CD4 testing, 65% did not complete it within 12 weeks of diagnosis. The higher the baseline CD4 cell count, the lower the odds of completing CD4 testing within 12 weeks. CONCLUSION: Patient losses between HIV testing, baseline CD4 cell count and the start of care and ART are high. As a result, many patients receive ART too late. Health information systems that link testing programmes with care and treatment programmes are needed.

Early loss to follow up after enrolment in pre-ART care at a large public clinic in Johannesburg, South Africa.

OBJECTIVE: To estimate loss to follow up (LTFU) between initial enrollment and the first scheduled return medical visit of a pre-antiretroviral therapy (ART) care program for patients not eligible for ART. METHODS: The study was conducted at a public-sector HIV clinic in Johannesburg. We reviewed records of all patients newly enrolled in the pre-ART care program and not yet eligible for ART between January 2007 and February 2008. Crude proportions of patients completing their first return medical visit stratified by patient characteristics were calculated. A modified-Poisson approach was used to estimate directly relative risks of returning for their first return medical visit within 1 year adjusting for patient characteristics as potential confounders. RESULTS: A total of 356 patients were identified. Two-thirds had a CD4 count > 350 cells/microl (median [IQR] CD4 = 458 [394, 585]) and were scheduled to return in 6 months for a first medical visit. Seventy-four percent of these patients did not return within one year for this visit. The remaining 36% of all patients had a baseline CD4 count 251-350 cells/microl and were scheduled to return in 3 months. Only 6% of these patients returned within 4 months; 41% returned within one year. Relative risks were positively associated with a patient being employed and negatively associated with the baseline CD4 count. CONCLUSIONS: Given the high rate of LTFU immediately after enrolling in pre-ART care, it is clear that care programs are not expediting the timely initiation of ART. Significantly improved adherence to pre-ART care and monitoring for patients not yet eligible for ART is required for South Africa to achieve its AIDS strategy goals and reduce the problem of late presentation and initiation of ART.

Improvements in physical wellbeing over the first two years on antiretroviral therapy in western Kenya.

Improvements in physical wellbeing during the first six months on antiretroviral therapy (ART) are well known, but little is known regarding long-term follow-up. We conducted a prospective cohort study among 222 HIV-positive adult tea plantation workers in western Kenya to assess wellbeing over their first two years on ART. Study subjects completed a standardized questionnaire during repeat ART clinic visits. A 30-day recall period was used to elicit the number of days when subjects experienced poor health and the number of days that pain made it difficult to complete usual activities at home and work. A seven-day recall period was used to assess the severity of bodily pain, nausea, fatigue, and rash. Prevalence of most symptoms declined over time. A median of seven days poor health during the first month on ART declined to three days in the 24th month (p=0.043). For pain making usual activities difficult, a median of seven days during the first month on ART fell to zero by 12 months (p< or =0.0001) but increased to three days by two years. Any bodily pain (range 59-83%) and fatigue (range 51-84%) over the past seven days were common through two years. However, pain and fatigue often over the past seven days declined over two years (from 24-10% (p=0.067) and 41-15% (p=0.002)). Skin rash was rare at all times, though higher at two years (8.6%) than any other time. Initial improvements in physical wellbeing were sustained over two years, however, increased pain and skin rash at year two may indicate problems as treatment programs mature. These improvements in physical wellbeing will be important in sustaining the long-term success of HIV treatment programs.

Prevalence of TB symptoms, diagnosis and treatment among people living with HIV (PLHIV) not on ART presenting at outpatient clinics in South Africa and Kenya: baseline results from a clinical trial.

OBJECTIVE: We used screening data and routine clinic records for intervention arm patients in the Simplified Algorithm for Treatment Eligibility (SLATE) trials to describe the prevalence of tuberculosis (TB) symptoms, diagnosis and treatment among people living with HIV (PLHIV), not on antiretroviral therapy (ART) and presenting at outpatient clinics in South Africa and Kenya. We compared the performance of the WHO four-symptom TB screening tool with a baseline Xpert test. SETTING: Outpatient HIV clinics in South Africa and Kenya. PARTICIPANTS: Eligible patients were non-pregnant, PLHIV, >18 years of age, not on ART, willing to provide written informed consent. A total of 594 patients in South Africa and 240 in Kenya were eligible. RESULTS: Prevalence of any TB symptom was 38% in Kenya, 35% (SLATE I) and 47% (SLATE II) in South Africa. During SLATE I, 70% of patients in Kenya and 57% in South Africa with ≥1 TB symptom were tested for TB. In SLATE II, 79% of patients with ≥1 TB symptom were tested. Of those, 19% tested positive for TB in Kenya, 15% (SLATE I) and 5% (SLATE II) tested positive in South Africa. Of the 28 patients who tested positive in both trials, 20 initiated TB treatment. The lowest median CD4 counts were among those with active TB (Kenya 124 cells/mm3; South Africa 193 cells/mm3). When comparing the WHO four-symptom screening tool to the Xpert test (SLATE II), we found that increasing the number of symptoms required for a positive screen from one to three or four decreased sensitivity but increased the positive predictive value to >30%. CONCLUSIONS: 80% of patients assessed for ART initiation presented with ≥1 TB symptoms. Reconsideration of the 'any symptom' rule may be appropriate, with ART initiation among patients with fewer/milder symptoms commencing while TB test results are pending. TRIAL REGISTRATION NUMBER: NCT02891135 and NCT03315013.

Will differentiated care for stable HIV patients reduce healthcare systems costs?

INTRODUCTION: South Africa's National Department of Health launched the National Adherence Guidelines for Chronic Diseases in 2015. These guidelines include adherence clubs (AC) and decentralized medication delivery (DMD) as two differentiated models of care for stable HIV patients on antiretroviral therapy. While the adherence guidelines do not suggest that provider costs (costs to the healthcare system for medications, laboratory tests and visits to clinics or alternative locations) for stable patients in these differentiated models of care will be lower than conventional, clinic-based care, recent modelling exercises suggest that such differentiated models could substantially reduce provider costs. In the context of continued implementation of the guidelines, we discuss the conditions under which provider costs of care for stable HIV patients could fall, or rise, with AC and DMD models of care in South Africa. DISCUSSION: In prior studies of HIV care and treatment costs, three main cost categories are antiretroviral medications, laboratory tests and general interaction costs based on encounters with health workers. Stable patients are likely to be on the national first-line regimen (Tenofovir/Entricitabine/Efavarinz (TDF/FTC/EFV)), so no difference in the costs of medications is expected. Laboratory testing guidelines for stable patients are the same regardless of the model of care, so no difference in laboratory costs is expected as well. Based on existing information regarding the costs of clinic visits, AC visits and DMD drug pickups, we expect that for some clinics, visit costs for DMD or AC models of care could be less, but modestly so, than for conventional, clinic-based care. For other clinics, however, DMD or AC models could have higher visit costs (see Table 2). CONCLUSIONS: The standard of care for stable patients has already been "differentiated" for years in South Africa, prior to the roll out of the new adherence guidelines. AC and DMD models of care, when implemented as envisioned in the guidelines, are unlikely to generate substantive reductions or increases in provider costs of care.

Cost-Effectiveness of Focal Mass Drug Administration and Mass Drug Administration with Dihydroartemisinin-Piperaquine for Malaria Prevention in Southern Province, Zambia: Results of a Community-Randomized Controlled Trial.

Community-wide administration of antimalarial drugs in therapeutic doses is a potential tool to prevent malaria infection and reduce the malaria parasite reservoir. To measure the effectiveness and cost of using the antimalarial drug combination dihydroartemisinin-piperaquine (DHAp) through different community-wide distribution strategies, Zambia's National Malaria Control Centre conducted a three-armed community-randomized controlled trial. The trial arms were as follows: 1) standard of care (SoC) malaria interventions, 2) SoC plus focal mass drug administration (fMDA), and 3) SoC plus MDA. Mass drug administration consisted of offering all eligible individuals DHAP, irrespective of a rapid diagnostic test (RDT) result. Focal mass drug administration consisted of offering DHAP to all eligible individuals who resided in a household where anyone tested positive by RDT. Results indicate that the costs of fMDA and MDA per person targeted and reached are similar (US$9.01 versus US$8.49 per person, respectively, P = 0.87), but that MDA was superior in all cost-effectiveness measures, including cost per infection averted, cost per case averted, cost per death averted, and cost per disability-adjusted life year averted. Subsequent costing of the MDA intervention in a non-trial, operational setting yielded significantly lower costs per person reached (US$2.90). Mass drug administration with DHAp also met the WHO thresholds for "cost-effective interventions" in the Zambian setting in 90% of simulations conducted using a probabilistic sensitivity analysis based on trial costs, whereas fMDA met these criteria in approximately 50% of simulations. A sensitivity analysis using costs from operational deployment and trial effectiveness yielded improved cost-effectiveness estimates. Mass drug administration may be a cost-effective intervention in the Zambian context and can help reduce the parasite reservoir substantially. Mass drug administration was more cost-effective in relatively higher transmission settings. In all scenarios examined, the cost-effectiveness of MDA was superior to that of fMDA.

Do the socioeconomic impacts of antiretroviral therapy vary by gender? A longitudinal study of Kenyan agricultural worker employment outcomes.

BACKGROUND: As access to antiretroviral therapy (ART) has grown in Africa, attention has turned to evaluating the socio-economic impacts of ART. One key issue is the extent to which improvements in health resulting from ART allows individuals to return to work and earn income. Improvements in health from ART may also be associated with reduced impaired presenteeism, which is the loss of productivity when an ill or disabled individual attends work but accomplishes less at his or her usual tasks or shifts to other, possibly less valuable, tasks. METHODS: Longitudinal data for this analysis come from company payroll records for 97 HIV-infected tea estate workers (the index group, 56 women, 41 men) and a comparison group of all workers assigned to the same work teams (n = 2485, 1691 men, 794 women) for a 37-month period covering two years before and one year after initiating ART. We used nearest neighbour matching methods to estimate the impacts of HIV/AIDS and ART on three monthly employment outcomes for tea estate workers in Kenya--days plucking tea, days assigned to non-plucking assignments, and kilograms harvested when plucking. RESULTS: The female index group worked 30% fewer days plucking tea monthly than the matched female comparison group during the final 9 months pre-ART. They also worked 87% more days on non-plucking assignments. While the monthly gap between the two groups narrowed after beginning ART, the female index group worked 30% fewer days plucking tea and about 100% more days on non-plucking tasks than the comparison group after one year on ART. The male index group was able to maintain a similar pattern of work as their comparison group except during the initial five months on therapy. CONCLUSION: Significant impaired presenteeism continued to exist among the female index group after one year on ART. Future research needs to explore further the socio-economic implications of HIV-infected female workers on ART being less productive than the general female workforce over sustained periods of time.