Assessment of facility-based tuberculosis data quality in an integrated HIV/TB database in three South African districts.

BACKGROUND: Assessment of data quality is essential to successful monitoring & evaluation of tuberculosis (TB) services. South Africa uses the Three Interlinked Electronic Register (TIER.Net) to monitor TB diagnoses and treatment outcomes. We assessed the quality of routine programmatic data as captured in TIER.Net. METHODS: We reviewed 277 records from routine data collected for adults who had started TB treatment for drug-sensitive (DS-) TB between 10/2018-12/2019 from 15 facilities across three South African districts using three sources and three approaches to link these (i.e., two approaches compared TIER.NET with the TB Treatment Record while the third approach compared all three sources of TB data: the TB treatment record or patient medical file; the TB Identification Register; and the TB module in TIER.Net). We report agreement and completeness of demographic information and key TB-related variables across all three data sources. RESULTS: In our first approach we selected 150 patient records from TIER.Net and found all but one corresponding TB Treatment Record (99%). In our second approach we were also able to find a corresponding TIER.Net record from a starting point of the paper-based, TB Treatment Record for 73/75 (97%) records. We found fewer records 55/75 (73%) in TIER.Net when we used as a starting point records from the TB Identification Register. Demographic information (name, surname, date of birth, and gender) was accurately reported across all three data sources (matching 90% or more). The reporting of key TB-related variables was similar across both the TB Treatment Record and the TB module in TIER.Net (p>0.05). We observed differences in completeness and moderate agreement (Kappa 0.41-0.60) for site of disease, TB treatment outcome and smear microscopy or X-ray as a diagnostic test (p<0.05). We observed more missing items for the TB Treatment record compared to TIER.Net; TB treatment outcome date and site of disease specifically. In comparison, TB treatment start dates as well as HIV-status recording had higher concordance. HIV status and lab results appeared to be more complete in the TB module in TIER.Net than in the TB Treatment Records, and there was "good/substantial" agreement (Kappa 0.61-0.80) for HIV status. DISCUSSION AND CONCLUSION: Our key finding was that the TB Module in TIER.Net was more complete in some key variables including TB treatment outcome. Most TB patient records we reviewed were found on TIER.Net but there was a noticeable gap of TB Identification patient records from the paper register as compared to TIER.Net, including those who tested TB-negative or HIV-negative. There is evidence of complete and "good/substantial" data quality for key TB-related variables, such as "First GeneXpert test result" and "HIV status." Improvements in data completeness of TIER.Net compared to the TB Treatment Record are the most urgent area for improvement, especially recording of TB treatment outcomes.

Performance of the Roche cobas MTB Assay for the Molecular Diagnosis of Pulmonary Tuberculosis in a High HIV Burden Setting.

Increased access to and improved sensitivities of methods for diagnosing Mycobacterium tuberculosis infection and detecting rifampicin and isoniazid resistance are needed. Herein, the performance of the new cobas MTB assay for use on cobas 6800/8800 Systems (Roche) was assessed and compared with two other commercial assays: RealTime MTB (Abbott), and Xpert MTB/RIF (Cepheid). Molecular PCR-based assays were conducted on sputum specimens from individuals with presumptive and confirmed tuberculosis (n = 294) from two clinical facilities in South Africa between December 2016 and October 2017. Liquid mycobacterial culture was the reference. Test sensitivities were 94.7% (95% CI, 88%-98%), 92.6% (95% CI, 85%-97%), and 91.6% (95% CI, 84%-96%) for cobas MTB, RealTime MTB, and Xpert MTB/RIF assays, respectively. cobas MTB sensitivity was unaffected by HIV coinfection (95.7%; 95% CI, 88%-99%; n = 176) and sediment testing (94.7%; 95% CI, 88%-98%). Sensitivities were 81.8% (95% CI, 60%-95%), 72.7% (95% CI, 50%-89%), and 72.7% (95% CI, 50%-89%) among smear-negative, culture-positive individuals (n = 221) for cobas MTB, RealTime MTB, and Xpert MTB/RIF assays, respectively. cobas MTB specificity was 95.7% (95% CI, 89%-99%) and 99% (95% CI, 94%-100%) among HIV coinfected and uninfected individuals, respectively. The cobas 6800/8800 system is already implemented in South Africa for high-throughput HIV viral load testing, making it suitable for integrated HIV/tuberculosis diagnostics.

Promoting Tuberculosis Preventive Therapy for People Living with HIV in South Africa: Interventions Hindered by Complicated Clinical Guidelines and Imbalanced Patient-Provider Dynamics.

Isoniazid preventive therapy (IPT) reduces the risk of active tuberculosis among people living with HIV, but implementation of IPT in South Africa and elsewhere remains slow. The objective of this study was to examine both nurse perceptions of clinical mentorship and patient perceptions of in-queue health education for promoting IPT uptake in Potchefstroom, South Africa. We measured adoption, fidelity, acceptability, and sustainability of the interventions using both quantitative and qualitative methods. Adoption, fidelity, and acceptability of the interventions were moderately high. However, nurses believed they could not sustain their increased prescriptions of IPT, and though many patients intended to ask nurses about IPT, few did. Most patients attributed their behavior to an imbalance of patient-provider power. National IPT guidelines should be unambiguous and easily implemented after minimal training on patient eligibility and appropriate medication durations, nurse-patient dynamics should empower the patient, and district-level support and monitoring should be implemented.

Intensified household contact tracing, prevention and treatment support versus enhanced standard of care for contacts of tuberculosis cases in South Africa: study protocol for a household cluster-randomised trial.

BACKGROUND: Household contact tracing of index TB cases has been advocated as a key part of TB control for many years, but has not been widely implemented in many low-resource setting because of the current dearth of high quality evidence for effectiveness. Innovative strategies for earlier, more effective treatment are particularly important in contexts with hyper-endemic levels of HIV, where levels of TB infection remain extremely high. METHODS: We present the design of a household cluster-randomised controlled trial of interventions aimed at improving TB-free survival and reducing childhood prevalence of Mycobacterium tuberculosis infection among household contacts of index TB cases diagnosed in two provinces of South Africa. Households of index TB cases will be randomly allocated in a 1:1 ratio to receive either an intensified home screening and linkage for TB and HIV intervention, or enhanced standard of care. The primary outcome will compare between groups the TB-free survival of household contacts over 15 months. All participants, or their next-of-kin, will provide written informed consent to participate. DISCUSSION: Evidence from randomised trials is required to identify cost-effective approaches to TB case-finding that can be applied at scale in sub-Saharan Africa. TRIAL REGISTRATION: ISRCTN16006202 (01/02/2017: retrospectively registered) and NHREC4399 (11/04/2016: prospectively registered). Protocol version: 4.0 (date: 18th January 2018).

Levofloxacin versus placebo for the prevention of tuberculosis disease in child contacts of multidrug-resistant tuberculosis: study protocol for a phase III cluster randomised controlled trial (TB-CHAMP).

BACKGROUND: Multidrug-resistant (MDR) tuberculosis (TB) presents a challenge for global TB control. Treating individuals with MDR-TB infection to prevent progression to disease could be an effective public health strategy. Young children are at high risk of developing TB disease following infection and are commonly infected by an adult in their household. Identifying young children with household exposure to MDR-TB and providing them with MDR-TB preventive therapy could reduce the risk of disease progression. To date, no trials of MDR-TB preventive therapy have been completed and World Health Organization guidelines suggest close observation with no active treatment. METHODS: The tuberculosis child multidrug-resistant preventive therapy (TB-CHAMP) trial is a phase III cluster randomised placebo-controlled trial to assess the efficacy of levofloxacin in young child contacts of MDR-TB cases. The trial is taking place at three sites in South Africa where adults with MDR-TB are identified. If a child aged < 5 years lives in their household, we assess the adult index case, screen all household members for TB disease and evaluate any child aged < 5 years for trial eligibility. Eligible children are randomised by household to receive daily levofloxacin (15-20 mg/kg) or matching placebo for six months. Children are closely monitored for disease development, drug tolerability and adverse events. The primary endpoint is incident TB disease or TB death by one year after recruitment. We will enrol 1556 children from approximately 778 households with an average of two eligible children per household. Recruitment will run for 18-24 months with all children followed for 18 months after treatment. Qualitative and health economic evaluations are embedded in the trial. DISCUSSION: If the TB-CHAMP trial demonstrates that levofloxacin is effective in preventing TB disease in young children who have been exposed to MDR-TB and that it is safe, well tolerated, acceptable and cost-effective, we would expect that that this intervention would rapidly transfer into policy. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN92634082 . Registered on 31 March 2016.

Influence of supply-side factors on voluntary medical male circumcision costs in Kenya, Rwanda, South Africa, and Zambia.

BACKGROUND: In this study, we described facility-level voluntary medical male circumcision (VMMC) unit cost, examined unit cost variation across facilities, and investigated key facility characteristics associated with unit cost variation. METHODS: We used data from 107 facilities in Kenya, Rwanda, South Africa, and Zambia covering 2011 or 2012. We used micro-costing to estimate economic costs from the service provider's perspective. Average annual costs per client were estimated in 2013 United States dollars (US$). Econometric analysis was used to explore the relationship between VMMC total and unit cost and facility characteristics. RESULTS: Average VMMC unit cost ranged from US$66 (SD US$79) in Kenya to US$160 (SD US$144) in South Africa. Total cost function estimates were consistent with economies of scale and scope. We found a negative association between the number of VMMC clients and VMMC unit cost with a 3% decrease in unit cost for every 10% increase in number of clients and we found a negative association between the provision of other HIV services and VMMC unit cost. Also, VMMC unit cost was lower in primary health care facilities than in hospitals, and lower in facilities implementing task shifting. CONCLUSIONS: Substantial efficiency gains could be made in VMMC service delivery in all countries. Options to increase efficiency of VMMC programs in the short term include focusing service provision in high yield sites when demand is high, focusing on task shifting, and taking advantage of efficiencies created by integrating HIV services. In the longer term, reductions in VMMC unit cost are likely by increasing the volume of clients at facilities by implementing effective demand generation activities.

Value stream mapping to characterize value and waste associated with accessing HIV care in South Africa.

INTRODUCTION: Inefficient clinic-level delivery of HIV services is a barrier to linkage and engagement in care. We used value stream mapping to quantify time spent on each component of a clinic visit while receiving care following a hospital admission in South Africa. METHODS: We described time for each clinic service ("process time") and time spent waiting for that service ("lead time"). We also determined time and patient costs associated with travel to the clinic and expenditures during the clinic visits for 15 clinic visits in South Africa. Participants were selected consecutively based on timing of scheduled clinic visit from a cohort of HIV-positive patients recently discharged from inpatient hospital care. During the mapping we asked the participants to assess challenges faced at the clinic visit. We subsequently conducted in depth interviews and included themes from the care experience in this analysis. RESULTS: The 15 clinic visits occurred at five clinics; four primary care and one hospital-based specialty clinic. Nine (64%) of the participants were women, the median age was 44 years (IQR: 32-49), three of the participants had one or more clinic visit in the prior 14 days, all but one participant was on antiretroviral therapy (ART) at the time of the clinic visit (ART was stopped following the hospital visit for that participant). The median time since hospital discharge was 131 days (interquartile range; IQR: 121-183) for the observed visits. The median travel time to and from the clinic to a place of residence was 60 minutes. The median time spent at the clinic was 3.5 hours (IQR: 2.5-5.3) of which 2.9 hours was lead time and 25 minutes was process time (registration, vital signs, clinician assessment, laboratory, and check-out). The median patient cost for transport and food while at the clinic was ZAR43/USD2.8 (median monthly household income in the district was ZAR2450/USD157). Participants highlighted long queues, repeat clinic visits, and multiple queues during the visit (median of 5 queues) as challenges. CONCLUSIONS: Accessing HIV care in South Africa is time consuming, complicated by multiple queues and frequent visits. A more patient-centered approach to care may decrease the burden of receiving care and improve outcomes.

Healthcare utilization for common infectious disease syndromes in Soweto and Klerksdorp, South Africa.

INTRODUCTION: Understanding healthcare utilization helps characterize access to healthcare, identify barriers and improve surveillance data interpretation. We describe healthcare-seeking behaviors for common infectious syndromes and identify reasons for seeking care. METHODS: We conducted a cross-sectional survey among residents in Soweto and Klerksdorp, South Africa. Households were interviewed about demographic characteristics; recent self-reported episodes of pneumonia, influenza-like illness (ILI), chronic febrile respiratory illness and meningitis in individuals of all ages; recent diarrhea in children aged < 5 years; and consultation with healthcare facilities and providers. RESULTS: From July-October 2012, we interviewed 1,442 households in Klerksdorp and 973 households in Soweto. Public clinics were consulted most frequently for pneumonia, ILI and diarrhea in a child <5 years old at both sites; public hospitals were most frequently consulted for chronic respiratory and meningitis syndromes. Of all illness episodes reported, there were 110 (35%) in Klerksdorp and 127 (32%) in Soweto for which the person did not seek care with a licensed medical provider. Pharmacies were often consulted by individuals with pneumonia (Klerksdorp: 17, 16%; Soweto: 38, 22%) or ILI (Klerksdorp: 35, 24%; 44, 28%). Patients who did not seek care with a licensed provider reported insufficient time (Klerksdorp: 7%; Soweto, 20%) and lack of medications at the facility (Klerksdorp: 4%; Soweto: 8%) as barriers. CONCLUSION: Public government healthcare facilities are commonly consulted for infectious syndromes and pharmacies are frequently consulted particularly for respiratory diseases. Improving medication availability at healthcare facilities and streamlining healthcare delivery may improve access of licensed providers for serious illnesses.

Improving active case finding for tuberculosis in South Africa: informing innovative implementation approaches in the context of the Kharitode trial through formative research.

BACKGROUND: Tuberculosis (TB) is the leading infectious killer worldwide, with approximately 1.8 million deaths in 2015. While effective treatment exists, implementation of active case finding (ACF) methods to identify persons with active TB in a timely and cost-effective manner continues to be a major challenge in resource-constrained settings. Limited qualitative work has been conducted to gain an in-depth understanding of implementation barriers. METHODS: Qualitative research was conducted to inform the development of three ACF strategies for TB to be evaluated as part of the Kharitode cluster-randomised trial being conducted in a rural province of South Africa. This included 25 semi-structured in-depth interviews among 8 TB patients, 7 of their household members and 10 clinic health workers, as well as 4 focus group discussions (2 rural and 2 main town locations) with 6-8 participants each (n = 27). Interviews and focus group discussions explored the context, advantages and limitations, as well as the implications of three ACF methods. Content analysis was utilised to document salient themes regarding their feasibility, acceptability and potential effectiveness. RESULTS: Study participants (TB patients and community members) reported difficulty identifying TB symptoms and seeking care in a timely fashion. In turn, all stakeholder groups felt that more proactive case finding strategies would be beneficial. Clinic-based strategies (including screening all patients regardless of visit purpose) were seen as the most acceptable method based on participants' preference ranking of the ACF strategies. However, given the resource constraints experienced by the public healthcare system in South Africa, many participants doubted whether it would be the most effective strategy. Household outreach and incentive-based strategies were described as promising, but participants reported some concerns (e.g. stigma in case of household-based and ethical concerns in the case of incentives). Participants offered insights into how to optimise each strategy, tailoring implementation to community needs (low TB knowledge) and realities (financial constraints, transport, time off from work). CONCLUSIONS: Findings suggest different methods of TB ACF are likely to engage different populations, highlighting the utility of a comprehensive approach. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT02808507 ). Registered June 1, 2016. The participants in this formative study are not trial participants.

Costs along the service cascades for HIV testing and counselling and prevention of mother-to-child transmission.

OBJECTIVE: We estimate facility-level average annual costs per client along the HIV testing and counselling (HTC) and prevention of mother-to-child transmission (PMTCT) service cascades. DESIGN: Data collected covered the period 2011-2012 in 230 HTC and 212 PMTCT facilities in Kenya, Rwanda, South Africa, and Zambia. METHODS: Input quantities and unit prices were collected, as were output data. Annual economic costs were estimated from the service providers' perspective using micro-costing. Average annual costs per client in 2013 United States dollars (US$) were estimated along the service cascades. RESULTS: For HTC, average cost per client tested ranged from US$5 (SD US$7) in Rwanda to US$31 (SD US$24) in South Africa, whereas average cost per client diagnosed as HIV-positive ranged from US$122 (SD US$119) in Zambia to US$1367 (SD US$2093) in Rwanda. For PMTCT, average cost per client tested ranged from US$18 (SD US$20) in Rwanda to US$89 (SD US$56) in South Africa; average cost per client diagnosed as HIV-positive ranged from US$567 (SD US$417) in Zambia to US$2021 (SD US$3210) in Rwanda; average cost per client on antiretroviral prophylaxis ranged from US$704 (SD US$610) in South Africa to US$2314 (SD US$3204) in Rwanda; and average cost per infant on nevirapine ranged from US$888 (SD US$884) in South Africa to US$2359 (SD US$3257) in Rwanda. CONCLUSION: We found important differences in unit costs along the HTC and PMTCT service cascades within and between countries suggesting that more efficient delivery of these services is possible.

Evaluating the cost of adult voluntary medical male circumcision in a mixed (surgical and PrePex) site compared to a hypothetical PrePex-only site in South Africa.

BACKGROUND: Several circumcision devices have been evaluated for a safe and simplified male circumcision among adults. The PrePex device was prequalified for voluntary male medical circumcision (VMMC) in May 2013 by the World Health Organization and is expected to simplify the procedure safely while reducing cost. South Africa is scaling up VMMC. OBJECTIVE: To evaluate the overall unit cost of VMMC at a mixed site vs. a hypothetical PrePex-only site in South Africa. DESIGN: We evaluated the overall unit cost of VMMC at a mixed site where PrePex VMMC procedure was added to routine forceps-guided scalpel-based VMMC in Soweto, South Africa. We abstracted costs and then modeled these costs for a hypothetical PrePex-only site, at which 9,600 PrePex circumcisions per year could be done. We examined cost drivers and modeled costs, varying the price of the PrePex device. The healthcare system perspective was used. RESULTS: In both sites, the main contributors of cost were personnel and consumables. If 10% of all VMMC were by PrePex at the mixed site, the overall costs of the surgical method and PrePex were similar - US$59.62 and $59.53, respectively. At the hypothetical PrePex-only site, the unit cost was US$51.10 with PrePex circumcisions having markedly lower personnel and biohazardous waste management costs. In sensitivity analysis with the cost of PrePex kit reduced to US$10 and $2, the cost of VMMC was further reduced. CONCLUSIONS: Adding PrePex to an existing site did not necessarily reduce the overall costs of VMMC. However, starting a new PrePex-only site is feasible and may significantly reduce the overall cost by lowering both personnel and capital costs, thus being cost-effective in the long term. Achieving a lower cost for PrePex will be an important contributor to the scale-up of VMMC.

A comparative assessment of the price, brands and pack characteristics of illicitly traded cigarettes in five cities and towns in South Africa.

OBJECTIVE: The prevalence of illicitly traded cigarettes in South Africa has been reported to be 40-50%. However, these estimates do not account for the more nuanced characteristics of the illicit cigarette trade. With the goal of better understanding contraband cigarettes in South Africa, this study piloted three methods for assessing the price, brands, pack features and smoker's views about illicit cigarettes in five cities/towns. Data were collected in June and July 2012. SETTING: A convenience sample of three South African cities (Johannesburg, Durban and Nelspruit) and two smaller towns (Musina and Ficksburg) were chosen for this study. OUTCOME MEASURES: Three cross-sectional approaches were used to assess the characteristics of contraband cigarettes: (1) a dummy purchase of cigarettes from informal retailers, (2) the collection of discarded cigarette packs and (3) a survey of tobacco smokers. PARTICIPANTS: For the purposes of the survey, 40 self-reported smokers were recruited at taxi ranks in each downtown site. Adults who were over the age of 18 were asked to verbally consent to participate in the study and answer a questionnaire administered by a researcher. RESULTS: The leading reason for labelling a pack as illicit in each city/town was the absence of an excise stamp (28.6% overall), and the least common reason was an illegal tar or nicotine level (11.1% overall). The overall proportion of informal vendors who sold illicit cigarettes was 41%. Singles and packs of 20 were consistently cheaper at informal vendors. Survey participants' responses reflected varied perspectives on illicit cigarettes and purchasing preferences. CONCLUSIONS: Each approach generated an interesting insight into physical aspects of illicit cigarettes. While this pilot study cannot be used to generate generalisable statistics on illicit cigarettes, more systematic surveys of this nature could inform researchers' and practitioners' initiatives to combat illicit and legal cigarette sales and usage.

Assessing cost and technical efficiency of HIV prevention interventions in sub-Saharan Africa: the ORPHEA study design and methods.

BACKGROUND: Scaling up services to achieve HIV targets will require that countries optimize the use of available funding. Robust unit cost estimates are essential for the better use of resources, and information on the heterogeneity in the unit cost of delivering HIV services across facilities - both within and across countries - is critical to identifying and addressing inefficiencies. There is limited information on the unit cost of HIV prevention services in sub-Saharan Africa and information on the heterogeneity within and across countries and determinants of this variation is even more scarce. The "Optimizing the Response in Prevention: HIV Efficiency in Africa" (ORPHEA) study aims to add to the empirical body of knowledge on the cost and technical efficiency of HIV prevention services that decision makers can use to inform policy and planning. METHODS/DESIGN: ORPHEA is a cross-sectional observational study conducted in 304 service delivery sites in Kenya, Rwanda, South Africa, and Zambia to assess the cost, cost structure, cost variability, and the determinants of efficiency for four HIV interventions: HIV testing and counselling (HTC), prevention of mother-to-child transmission (PMTCT), voluntary medical male circumcision (VMMC), and HIV prevention for sex workers. ORPHEA collected information at three levels (district, facility, and individual) on inputs to HIV prevention service production and their prices, outputs produced along the cascade of services, facility-level characteristics and contextual factors, district-level factors likely to influence the performance of facilities as well as the demand for HIV prevention services, and information on process quality for HTC, PMTCT, and VMMC services. DISCUSSION: ORPHEA is one of the most comprehensive studies on the cost and technical efficiency of HIV prevention interventions to date. The study applied a robust methodological design to collect comparable information to estimate the cost of HTC, PMTCT, VMMC, and sex worker prevention services in Kenya, Rwanda, South Africa, and Zambia, the level of efficiency in the current delivery of these services, and the key determinants of efficiency. The results of the study will be important to decision makers in the study countries as well as those in countries facing similar circumstances and contexts.

Mortality associated with delays between clinic entry and ART initiation in resource-limited settings: results of a transition-state model.

OBJECTIVE: To estimate the mortality impact of delay in antiretroviral therapy (ART) initiation from the time of entry into care. DESIGN: A state-transition Markov process model. This technique allows for assessing mortality before and after ART initiation associated with delays in ART initiation among a general population of ART-eligible patients without conducting a randomized trial. METHODS: We used patient-level data from 3 South African cohorts to determine transition probabilities for pre-ART CD4 count changes and pre-ART and on-ART mortality. For each parameter, we generated probabilities and distributions for Monte Carlo simulations with 1-week cycles to estimate mortality 52 weeks from clinic entry. RESULTS: We estimated an increase in mortality from 11.0% to 14.7% (relative increase of 34%) with a 10-week delay in ART for patients entering care with our pre-ART cohort CD4 distribution. When we examined low CD4 ranges, the relative increase in mortality delays remained similar; however, the absolute increase in mortality rose. For example, among patients entering with CD4 count 50-99 cells per cubic millimeter, 12-month mortality increased from 13.3% with no delay compared with 17.0% with a 10-week delay and 22.9% with a 6-month delay. CONCLUSIONS: Delays in ART initiation, common in routine HIV programs, can lead to important increases in mortality. Prompt ART initiation for patients entering clinical care and eligible for ART, especially those with lower CD4 counts, could be a relatively low-cost approach with a potential marked impact on mortality.

The clinical and economic impact of genotype testing at first-line antiretroviral therapy failure for HIV-infected patients in South Africa.

BACKGROUND: In resource-limited settings, genotype testing at virologic failure on first-line antiretroviral therapy (ART) may identify patients with wild-type (WT) virus. After adherence counseling, these patients may safely and effectively continue first-line ART, thereby delaying more expensive second-line ART. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications International model of human immunodeficiency virus (HIV) disease to simulate a South African cohort of HIV-infected adults at first-line ART failure. Two strategies were examined: no genotype vs genotype, assuming availability of protease inhibitor-based second-line ART. Model inputs at first-line ART failure were mean age 38 years, mean CD4 173/µL, and WT virus prevalence 20%; genotype cost was $300 per test and delay to results, 3 months. Outcomes included life expectancy, per-person costs (2010 US dollars), and incremental cost-effectiveness ratios (dollars per years of life saved [YLS]). RESULTS: No genotype had a projected life expectancy of 106.1 months, which with genotype increased to 108.3 months. Per-person discounted lifetime costs were $16 360 and $16 540, respectively. Compared to no genotype, genotype was very cost-effective, by international guidance, at $900/YLS. The cost-effectiveness of genotype was sensitive to prevalence of WT virus (very cost-effective when prevalence ≥ 12%), CD4 at first-line ART failure, and ART efficacy. Genotype-associated delays in care ≥ 5 months decreased survival and made no genotype the preferred strategy. When the test cost was <$100, genotype became cost-saving. CONCLUSIONS: Genotype resistance testing at first-line ART failure is very cost-effective in South Africa. The cost-effectiveness of this strategy will depend on prevalence of WT virus and timely response to genotype results.

Rates and cost of hospitalization before and after initiation of antiretroviral therapy in urban and rural settings in South Africa.

Few studies have compared hospitalizations before and after antiretroviral therapy (ART) initiation in the same patients. We analyzed the cost of hospitalizations among 3906 adult patients in 2 South African hospitals, 30% of whom initiated ART. Hospitalizations were 50% and 40% more frequent and 1.5 and 2.6 times more costly at a CD4 cell count, 100 cells/mm(3) when compared with 200­350 cells/mm(3) in the pre-ART and ART period, respectively. Mean inpatient cost per patient year was USD 117 (95%confidence interval, 85 to 158) for patients on ART and USD 72(95% confidence interval, 56 to 89) for pre-ART patients. Raising ART eligibility thresholds could avoid the high cost of hospitalization before and immediately after ART initiation.

Costs of inpatient treatment for multi-drug-resistant tuberculosis in South Africa.

BACKGROUND: In South Africa, patients with multi-drug-resistant tuberculosis (MDR-TB) are hospitalised from MDR-TB treatment initiation until culture conversion. Although MDR-TB accounts for <3% of incident TB in South Africa, 55% of the public sector TB budget is spent on MDR-TB. To inform new strategies for MDR-TB management, we estimated the per-patient cost (USD 2011) of inpatient MDR-TB treatment. METHODS: All resources used by patients admitted to the MDR-TB hospital with confirmed MDR-TB from March 2009 to February 2010 were abstracted from patient records for up to 12 months after initial admission or until the earliest of final discharge, abscondment or death. Costs of hospital stay/day were estimated from hospital expenditure records and costs for drugs, laboratory tests, radiography and surgery from public sector sources. 133 patients met study inclusion criteria of whom 121 had complete cost records. RESULTS: By 12 months, 86% were discharged with culture conversion, 8% died in hospital, 2% were still admitted, and 3% had absconded. The mean hospital stay was 105 days. The mean total cost per patient was $17 164, of which 95% were hospitalisation costs (buildings, staff, etc.) and ≤ 2% each for MDR-TB drugs ($380); TB laboratory tests, including drug susceptibility testing ($236); and other costs. CONCLUSIONS: The inpatient cost per patient treated for MDR-TB is more than 40 times the cost of treating drug-susceptible TB in South Africa. There is potential for substantial cost savings from improved management of drug-susceptible TB and shifting to a model of decentralised, outpatient MDR-treatment.

Designing family-centered male circumcision services: a conjoint analysis approach.

BACKGROUND: Male circumcision (MC) has become an important weapon in the fight against HIV/AIDS in many Sub-Saharan African countries. The successful implementation of a national MC program requires the design of circumcision services that are attractive to young men of various ages. For many potential clients, mothers and/or fathers will play an important role in the decision to be circumcised, and hence services will need to be designed with the preferences of mothers, fathers, and sons in mind. OBJECTIVE: Our objective was to value multiple design characteristics of potential community-based MC services from the perspectives of mothers, fathers, and sons in Johannesburg, South Africa, and to test for concordance between their values for the design characteristics. METHODS: Potential design characteristics of MC services were identified through open-ended interviews with key informants (n = 25). Preferences were estimated using conjoint analysis implemented as part of a cluster randomized household survey. Each participant was randomized to receive one of two possible blocks of conjoint analysis, each consisting of six forced-choice tasks comparing two possible MC services varying on 11 design characteristics. With only two levels for each attribute, our experimental design utilized a main effects orthogonal array. Data were analyzed using linear probability models, with tests of concordance of values using Wald tests generated from stratified estimates calculated using restricted least square estimation. RESULTS: A racially and geographically diverse sample consisting of 204 fathers, 204 mothers, and 237 sons completed the survey. In aggregate, requiring a follow-up visit was the most valued design factor (p < 0.001), followed by having a lower infection rate (p < 0.001), having less pain (p = 0.001), and a private waiting room (p = 0.001). Based on stratified analysis, sons also valued having the risks and benefits of MC explained (p = 0.01) and mothers valued requiring an HIV test as part of the procedure. Requiring an HIV test was the most significant difference between the respondents (p = 0.03), with sons finding it somewhat repulsive (p = 0.30). CONCLUSION: Our findings suggest that valuation of aspects of MC clinic design can diverge by decision maker. To better ensure utilization of services, these variations should be taken into account to prior to implementation of a national strategy in South Africa.

Sexual risk behaviors among HIV-infected South African men and women with their partners in a primary care program: implications for couples-based prevention.

We studied 1163 sexually-active HIV-infected South African men and women in an urban primary care program to understand patterns of sexual behaviors and whether these behaviors differed by partner HIV status. Overall, 40% reported a HIV-positive partner and 60% a HIV-negative or status unknown partner; and 17.5% reported >2 sex acts in the last 2 weeks, 16.4% unprotected sex in the last 6 months, and 3.7% >1 sex partner in the last 6 months. Antiretroviral therapy (ART) was consistently associated with decreased sexual risk behaviors, as well as with reporting a HIV-negative or status unknown partner. The odds of sexual risk behaviors differed by sex; and were generally higher among participants reporting a HIV-positive partner, but continued among those with a HIV-negative or status unknown partner. These data support ART as a means of HIV prevention. Engaging in sexual risk behaviors primarily with HIV-positive partners was not widely practiced in this setting, emphasizing the need for couples-based prevention.

Parametric variable selection in generalized partially linear models with an application to assess condom use by HIV-infected patients.

To study significant predictors of condom use in HIV-infected adults, we propose the use of generalized partially linear models and develop a variable selection procedure incorporating a least squares approximation. Local polynomial regression and spline smoothing techniques are used to estimate the baseline nonparametric function. The asymptotic normality of the resulting estimate is established. We further demonstrate that, with the proper choice of the penalty functions and the regularization parameter, the resulting estimate performs as well as an oracle procedure. Finite sample performance of the proposed inference procedure is assessed by Monte Carlo simulation studies. An application to assess condom use by HIV-infected patients gains some interesting results, which cannot be obtained when an ordinary logistic model is used.