The met and unmet health needs for HIV, hypertension, and diabetes in rural KwaZulu-Natal, South Africa: analysis of a cross-sectional multimorbidity survey.

BACKGROUND: The convergence of infectious diseases and non-communicable diseases in South Africa is challenging to health systems. In this analysis, we assessed the multimorbidity health needs of individuals and communities in rural KwaZulu-Natal and established a framework to quantify met and unmet health needs for individuals living with infectious and non-communicable diseases. METHODS: We analysed data collected between May 25, 2018, and March 13, 2020, from participants of a large, community-based, cross-sectional multimorbidity survey (Vukuzazi) that offered community-based HIV, hypertension, and diabetes screening to all residents aged 15 years or older in a surveillance area in the uMkhanyakude district in KwaZulu-Natal, South Africa. Data from the Vukuzazi survey were linked with data from demographic and health surveillance surveys with a unique identifier common to both studies. Questionnaires were used to assess the diagnosed health conditions, treatment history, general health, and sociodemographic characteristics of an individual. For each condition (ie, HIV, hypertension, and diabetes), individuals were defined as having no health needs (absence of condition), met health needs (condition that is well controlled), or one or more unmet health needs (including diagnosis, engagement in care, or treatment optimisation). We analysed met and unmet health needs for individual and combined conditions and investigated their geospatial distribution. FINDINGS: Of 18 041 participants who completed the survey (12 229 [67·8%] were female and 5812 [32·2%] were male), 9898 (54·9%) had at least one of the three chronic diseases measured. 4942 (49·9%) of these 9898 individuals had at least one unmet health need (1802 [18·2%] of 9898 needed treatment optimisation, 1282 [13·0%] needed engagement in care, and 1858 [18·8%] needed a diagnosis). Unmet health needs varied by disease; 1617 (93·1%) of 1737 people who screened positive for diabetes, 2681 (58·2%) of 4603 people who screened positive for hypertension, and 1321 (21·7%) of 6096 people who screened positive for HIV had unmet health needs. Geospatially, met health needs for HIV were widely distributed and unmet health needs for all three conditions had specific sites of concentration; all three conditions had an overlapping geographical pattern for the need for diagnosis. INTERPRETATION: Although people living with HIV predominantly have a well controlled condition, there is a high burden of unmet health needs for people living with hypertension and diabetes. In South Africa, adapting current, widely available HIV care services to integrate non-communicable disease care is of high priority. FUNDING: Fogarty International Center and the National Institutes of Health, the Bill & Melinda Gates Foundation, the South African Department of Science and Innovation, the South African Medical Research Council, the South African Population Research Infrastructure Network, and the Wellcome Trust. TRANSLATION: For the isiZulu translation of the abstract see Supplementary Materials section.

Human resource time commitments and associated costs of Community Caregiver outreach team operations in South Africa.

INTRODUCTION: In South Africa, Community Caregivers (CCGs) visit households to provide basic healthcare services including those for tuberculosis and HIV. However, CCG workloads, costs, and time burden are largely unknown. Our objective was to assess the workloads and operational costs for CCG teams operating in different settings in South Africa. METHODS: Between March and October 2018, we collected standardized self-reported activity time forms from 11 CCG pairs working at two public health clinics in Ekurhuleni district, South Africa. CCG workloads were assessed based on activity unit times, per-household visit time, and mean daily number of successful household visits. Using activity-based times and CCG operating cost data, we assessed CCG annual and per-household visit costs (USD 2019) from the health system perspective. RESULTS: CCGs in clinic 1 (peri-urban, 7 CCG pairs) and 2 (urban, informal settlement; 4 CCG pairs) served an area of 3.1 km2 and 0.6 km2 with 8,035 and 5,200 registered households, respectively. CCG pairs spent a median 236 minutes per day conducting field activities at clinic 1 versus 235 minutes at clinic 2. CCG pairs at clinic 1 spent 49.5% of this time at households (versus traveling), compared to 35.0% at clinic 2. On average, CCG pairs successfully visited 9.5 vs 6.7 households per day for clinics 1 and 2, respectively. At clinic 1, 2.7% of household visits were unsuccessful, versus 28.5% at clinic 2. Total annual operating costs were higher in clinic 1 ($71,780 vs $49,097) but cost per successful visit was lower ($3.58) than clinic 2 ($5.85). CONCLUSIONS: CCG home visits were more frequent, successful, and less costly in clinic 1, which served a larger and more formalized settlement. The variability in workload and cost observed across pairs and clinics suggests that circumstantial factors and CCG needs must be carefully assessed for optimized CCG outreach operations.

Cost-effectiveness of tuberculosis infection prevention and control interventions in South African clinics: a model-based economic evaluation informed by complexity science methods.

INTRODUCTION: Nosocomial Mycobacterium tuberculosis (Mtb) transmission substantially impacts health workers, patients and communities. Guidelines for tuberculosis infection prevention and control (TB IPC) exist but implementation in many settings remains suboptimal. Evidence is needed on cost-effective investments to prevent Mtb transmission that are feasible in routine clinic environments. METHODS: A set of TB IPC interventions was codesigned with local stakeholders using system dynamics modelling techniques that addressed both core activities and enabling actions to support implementation. An economic evaluation of these interventions was conducted at two clinics in KwaZulu-Natal, employing agent-based models of Mtb transmission within the clinics and in their catchment populations. Intervention costs included the costs of the enablers (eg, strengthened supervision, community sensitisation) identified by stakeholders to ensure uptake and adherence. RESULTS: All intervention scenarios modelled, inclusive of the relevant enablers, cost less than US$200 per disability-adjusted life-year (DALY) averted and were very cost-effective in comparison to South Africa's opportunity cost-based threshold (US$3200 per DALY averted). Two interventions, building modifications to improve ventilation and maximising use of the existing Central Chronic Medicines Dispensing and Distribution system to reduce the number of clinic attendees, were found to be cost saving over the 10-year model time horizon. Incremental cost-effectiveness ratios were sensitive to assumptions on baseline clinic ventilation rates, the prevalence of infectious TB in clinic attendees and future HIV incidence but remained highly cost-effective under all uncertainty analysis scenarios. CONCLUSION: TB IPC interventions in clinics, including the enabling actions to ensure their feasibility, afford very good value for money and should be prioritised for implementation within the South African health system.

Using system dynamics modelling to estimate the costs of relaxing health system constraints: a case study of tuberculosis prevention and control interventions in South Africa.

Health system constraints are increasingly recognized as an important addition to model-based analyses of disease control interventions, as they affect achievable impact and scale. Enabling activities implemented alongside interventions to relax constraints and reach the intended coverage may incur additional costs, which should be considered in priority setting decisions. We explore the use of group model building, a participatory system dynamics modelling technique, for eliciting information from key stakeholders on the constraints that apply to tuberculosis infection prevention and control processes within primary healthcare clinics in South Africa. This information was used to design feasible interventions, including the necessary enablers to relax existing constraints. Intervention and enabler costs were then calculated at two clinics in KwaZulu-Natal using input prices and quantities from the published literature and local suppliers. Among the proposed interventions, the most inexpensive was retrofitting buildings to improve ventilation (US$1644 per year), followed by maximizing the use of community sites for medication collection among stable patients on antiretroviral therapy (ART; US$3753) and introducing appointments systems to reduce crowding (US$9302). Enablers identified included enhanced staff training, supervision and patient engagement activities to support behaviour change and local ownership. Several of the enablers identified by the stakeholders, such as obtaining building permissions or improving information flow between levels of the health systems, were not amenable to costing. Despite this limitation, an approach to costing rooted in system dynamics modelling can be successfully applied in economic evaluations to more accurately estimate the 'real world' opportunity cost of intervention options. Further empirical research applying this approach to different intervention types (e.g. new preventive technologies or diagnostics) may identify interventions that are not cost-effective in specific contexts based on the size of the required investment in enablers.

Strengthening health systems to improve the value of tuberculosis diagnostics in South Africa: A cost and cost-effectiveness analysis.

BACKGROUND: In South Africa, replacing smear microscopy with Xpert-MTB/RIF (Xpert) for tuberculosis diagnosis did not reduce mortality and was cost-neutral. The unchanged mortality has been attributed to suboptimal Xpert implementation. We developed a mathematical model to explore how complementary investments may improve cost-effectiveness of the tuberculosis diagnostic algorithm. METHODS: Complementary investments in the tuberculosis diagnostic pathway were compared to the status quo. Investment scenarios following an initial Xpert test included actions to reduce pre-treatment loss-to-follow-up; supporting same-day clinical diagnosis of tuberculosis after a negative result; and improving access to further tuberculosis diagnostic tests following a negative result. We estimated costs, deaths and disability-adjusted-life-years (DALYs) averted from provider and societal perspectives. Sensitivity analyses explored the mediating influence of behavioural, disease- and organisational characteristics on investment effectiveness. FINDINGS: Among a cohort of symptomatic patients tested for tuberculosis, with an estimated active tuberculosis prevalence of 13%, reducing pre-treatment loss-to-follow-up from ~20% to ~0% led to a 4% (uncertainty interval [UI] 3; 4%) reduction in mortality compared to the Xpert scenario. Improving access to further tuberculosis diagnostic tests from ~4% to 90% among those with an initial negative Xpert result reduced overall mortality by 28% (UI 27; 28) at $39.70/ DALY averted. Effectiveness of investment scenarios to improve access to further diagnostic tests was dependent on a high return rate for follow-up visits. INTERPRETATION: Investing in direct and indirect costs to support the TB diagnostic pathway is potentially highly cost-effective.

Patient costs incurred by people living with HIV/AIDS prior to ART initiation in primary healthcare facilities in Gauteng, South Africa.

PURPOSE: To quantify costs to patients of accessing HIV care prior to ART initiation. MATERIALS AND METHODS: Using a cross-sectional study design, costs incurred by HIV-positive patients prior to ART initiation were estimated at urban primary healthcare facilities in South Africa. Costs included direct costs, indirect (productivity) costs, carer and coping costs (value of assets sold and money borrowed). The percentage of individual income spent on healthcare was calculated and compared by patient income tertiles and CD4 count strata. RESULTS: 289 patients (69% female, mean age 37 (SD: 10) years, median CD4 317 (IQR: 138-494) cells/mm3) were interviewed. The total mean monthly cost of pre-ART care was US$15.71. Indirect costs accounted for $2.59 (16.49%) of this when time was valued using the patient's reported income. The mean monthly patient costs were $31.61, $12.78, $12.65 and $11.93 for those with a CD4 count <100, 101-350, 351-500 and >500 cells/mm3 respectively. The percentage of individual income spent on healthcare was 7.25% for those with a CD4 count <100 cells/mm3 and 4.05% for those with a CD4 count >500 cells/mm3. CONCLUSIONS: Despite the provision of charge-free services at public clinics, care prior to ART initiation can be costly, particularly for the poor and unemployed. Our study adds to the growing body of evidence that highlights the need to consider policies to reduce the economic barriers to HIV service access, particularly for low income or unwell patient groups, such as improving access to disability grants.

Measuring income for catastrophic cost estimates: Limitations and policy implications of current approaches.

There is increasing global policy interest in estimating catastrophic costs incurred by households because of ill health, and growing need for information on disease-specific household cost data. There are several methodological approaches used to estimate income and no current consensus on the best method for estimating income in the context of a survey at the health facility. We compared six different approaches to estimate catastrophic cost among patients attending a health facility in South Africa. We used patient cost and income data collected June 2014-March 2015 from 66 participants enrolled in a clinical trial in South Africa (TB FastTrack) to explore the variation arising from different income estimation approaches and compared the number of households encountering catastrophic costs derived for each approach. The total proportion of households encountering catastrophic costs varied from 0% to 36%, depending on the estimation method. Self-reported mean annual income was significantly lower than permanent income estimated using an asset linking approach, or income estimated using the national average. A disproportionate number of participants adopting certain coping strategies, including selling assets and taking loans, were unable to provide self-reported income data. We conclude that the rapid methods for estimating income among patients attending a health facility are currently inconsistent. Further research on methods for measuring income, comparing the current recommended methods to 'gold standard' methods in different settings, should be done to identify the most appropriate measurement method.

The patient costs of care for those with TB and HIV: a cross-sectional study from South Africa.

BACKGROUND: This study describes the post-diagnosis care-seeking costs incurred by people living with TB and/or HIV and their households, in order to identify the potential benefits of integrated care. METHODS: We conducted a cross-sectional study with 454 participants with TB or HIV or both in public primary health care clinics in Ekurhuleni North Sub-District, South Africa. We collected information on visits to health facilities, direct and indirect costs for participants and for their guardians and caregivers. We define 'integration' as receipt of both TB and HIV services at the same facility, on the same day. Costs were presented and compared across participants with TB/HIV, TB-only and HIV-only. Costs exceeding 10% of participant income were considered catastrophic. RESULTS: Participants with both TB and HIV faced a greater economic burden (US$74/month) than those with TB-only (US$68/month) or HIV-only (US$40/month). On average, people with TB/HIV made 18.4 visits to health facilities, more than TB-only participants or HIV-only participants who made 16 and 5.1 visits, respectively. However, people with TB/HIV had fewer standalone TB (10.9) and HIV (2.2) visits than those with TB-only (14.5) or HIV-only (4.4). Although people with TB/HIV had access to 'integrated' services, their time loss was substantially higher than for other participants. Overall, 55% of participants encountered catastrophic costs. Access to official social protection schemes was minimal. CONCLUSIONS: People with TB/HIV in South Africa are at high risk of catastrophic costs. To some extent, integration of services reduces the number of standalone TB and HIV of visits to the health facility. It is however unlikely that catastrophic costs can be averted by service integration alone. Our results point to the need for timely social protection, particularly for HIV-positive people starting TB treatment.

Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models.

BACKGROUND: The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. METHODS: We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016-35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice. FINDINGS: Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective. INTERPRETATION: Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary. FUNDING: Bill & Melinda Gates Foundation.

Clinic-level factors influencing patient outcomes on antiretroviral therapy in primary health clinics in South Africa.

OBJECTIVES: To explore which clinic-level factors influence treatment outcomes in a multisite antiretroviral therapy (ART) programme in South Africa. DESIGN: Retrospective cohort study using 36 clinics. METHODS: We used random effects modelling to investigate clinic-level factors influencing ART outcomes, adjusting for patient-level factors and accounting for clustering at clinic level. Outcomes were unsuppressed viral load (>400 copies/ml) at 24 months after ART start and time to loss to follow-up. RESULTS: At clinic level, the mean proportion of patients with unsuppressed viral load at 24 months was 16% (range 8-33%). Loss to follow-up was also highly variable across clinics ranging from 3.5 to 23.4/100 person-years. Unsuppressed viral load was associated with a lower doctor-patient ratio [for every 500 patients, compared with >2.6 doctors: <0.7 doctors: adjusted odds ratio (OR) 1.52, 95% confidence interval (CI) 1.04-2.21; 0.7-2.6 doctors, OR 1.33, CI 0.91-1.93, P trend 0.04] after adjustment for patient factors. Combinations of psychosocial support interventions were weakly associated with reduced loss to follow-up [>6 interventions vs. <4 interventions: hazard ratio 0.39 (CI 0.15 - 1.04), P = 0.11]. Flexibility of services, integration of services, staff motivation, staff leadership and location of clinic were not consistently associated with improved outcomes. CONCLUSION: The dominant clinic-level influences on patient outcomes were doctor : patient ratio, and combination interventions to reduce loss to follow-up. Further research is needed to define optimum staffing levels that are required to roll out ART and the combination intervention that is most effective to reduce loss to follow-up.

Missed Opportunities for TB Investigation in Primary Care Clinics in South Africa: Experience from the XTEND Trial.

SETTING: 40 primary health clinics (PHCs) in four provinces in South Africa, June 2012 -February 2013. OBJECTIVE: To determine whether health care worker (HCW) practice in investigating people with TB symptoms was altered when the initial test for TB was changed from smear microscopy to Xpert MTB/RIF. DESIGN: Cross-sectional substudy at clinics participating in a pragmatic cluster randomised trial, Xpert for TB: Evaluating a New Diagnostic "XTEND", which evaluated the effect of Xpert MTB/RIF implementation in South Africa. METHODS: Consecutive adults exiting PHCs reporting at least one TB symptom (defined as any of cough, weight loss, night sweats and fever) were enrolled. The main outcome was the proportion who self-reported having sputum requested by HCW during the clinic encounter just completed. RESULTS: 3604 adults exiting PHCs (1676 in Xpert arm, 1928 in microscopy arm) were enrolled (median age 38 years, 71.4% female, 38.8% reported being HIV-positive, 70% reported cough). For 1267 participants (35.2%) the main reason for attending the clinic was TB symptom(s). Overall 2130/3604 (59.1%) said they reported their symptom(s) to HCW. 22.7% (818/3604) reported having been asked to give sputum for TB investigation. Though participants in the Xpert vs. microscopy arm were more likely to have sputum requested by HCW, this was not significantly different: overall (26.0% [436/1676] vs 19.8% [382/1928]; adjusted prevalence ratio [aPR] 1.31, [95% CI 0.78-2.20]) and when restricted to those presenting at clinics due to symptoms (49.1% [260/530] vs 29.9% [220/737]; aPR 1.38 [0.89-2.13]) and those reporting being HIV-positive (29.4% [190/647] vs 20.8% [156/749]; aPR 1.38[0.88-2.16]). Those attending clinic due to TB symptoms, were more likely to have sputum requested if they had increasing number of symptoms; longer duration of cough, unintentional weight loss and night sweats and if they reported symptoms to HCW. CONCLUSIONS: A large proportion of people exiting PHCs reporting TB symptoms did not get tested. Implementation of Xpert MTB/RIF did not substantially change the probability of testing for TB. Better systems are needed to ensure that opportunities to identify active TB among PHC attendees are not missed.

Linking women who test HIV-positive in pregnancy-related services to HIV care and treatment services in Kenya: a mixed methods prospective cohort study.

INTRODUCTION: There has been insufficient attention to long-term care and treatment for pregnant women diagnosed with HIV. OBJECTIVE AND METHODS: This prospective cohort study of 100 HIV-positive women recruited within pregnancy-related services in a district hospital in Kenya employed quantitative methods to assess attrition between women testing HIV-positive in pregnancy-related services and accessing long-term HIV care and treatment services. Qualitative methods were used to explore barriers and facilitators to navigating these services. Structured questionnaires were administered to cohort participants at enrolment and 90+ days later. Participants' medical records were monitored prospectively. Semi-structured qualitative interviews were carried out with a sub-set of 19 participants. FINDINGS: Only 53/100 (53%) women registered at an HIV clinic within 90 days of HIV diagnosis, of whom 27/53 (51%) had a CD4 count result in their file. 11/27 (41%) women were eligible for immediate antiretroviral therapy (ART); only 6/11 (55%) started ART during study follow-up. In multivariable logistic regression analysis, factors associated with registration at the HIV clinic within 90 days of HIV diagnosis were: having cared for someone with HIV (aOR:3.67(95%CI:1.22, 11.09)), not having to pay for transport to the hospital (aOR:2.73(95%CI:1.09, 6.84)), and having received enough information to decide to have an HIV test (aOR:3.61(95%CI:0.83, 15.71)). Qualitative data revealed multiple factors underlying high patient drop-out related to women's social support networks (e.g. partner's attitude to HIV status), interactions with health workers (e.g. being given unclear/incorrect HIV-related information) and health services characteristics (e.g. restricted opening hours, long waiting times). CONCLUSION: HIV testing within pregnancy-related services is an important entry point to HIV care and treatment services, but few women successfully completed the steps needed for assessment of their treatment needs within three months of diagnosis. Programmatic recommendations include simplified pathways to care, better-tailored counselling, integration of ART into antenatal services, and facilitation of social support.

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.

Integrating tuberculosis and HIV services in low- and middle-income countries: a systematic review.

OBJECTIVES: Given the imperative to scale up integrated tuberculosis (TB) and HIV services in settings where both are of major public health importance, we aimed to synthesise knowledge concerning implementation of TB/HIV service integration. METHODS: Systematic review of studies describing a strategy to facilitate TB and HIV service integration, searching 15 bibliographic databases including Medline, Embase and the Cochrane library; and relevant conference abstracts. RESULTS: Sixty-three of 1936 peer-reviewed articles and 70 of 170 abstracts met our inclusion criteria. We identified five models: entry via TB service, with referral for HIV testing and care; entry via TB service, on-site HIV testing, and referral for HIV care; entry via HIV service with referral for TB screening and treatment; entry via HIV service, on-site TB screening, and referral for TB diagnosis and treatment; and TB and HIV services provided at a single facility. Referral-based models are most easily implemented, but referral failure is a key risk. Closer integration requires more staff training and additional infrastructure (e.g. private space for HIV counselling; integrated records). Infection control is a major concern. More integrated models hold potential efficiencies from both provider and user perspective. Most papers report 'outcomes' (e.g. proportion of TB patients tested for HIV); few report downstream 'impacts' such as outcomes of TB treatment or antiretroviral therapy. Very few studies address the perspectives of service users or staff, or costs or cost-effectiveness. CONCLUSIONS: While scaling up integrated services, robust comparisons of the impacts of different models are needed using standardised outcome measures.

A novel HIV treatment model using private practitioners in South Africa.

OBJECTIVES: The extent of the HIV epidemic in South Africa may render the public sector capacity inadequate to manage all patients requiring antiretroviral treatment (ART). Private practitioners are an underutilised resource. METHODS: The authors developed a model of care using 72 private practitioners in five provinces in urban and rural areas of South Africa with centralised clinical support, training, pharmacy control and data management. The authors describe the programme, its quality control measures and patient outcomes using a cohort analysis. RESULTS: Between January 2005 and December 2008, 9102 individuals were started on ART, 62% female, median age 34 years, median viral load 50,655 copies/ml and median baseline CD4 count 123 cells/µl. Retention (alive and in care) after 12 months was 63% in the 2005 cohort (646 of 1026) and remained similar in the other calendar years, 58%, 68% and 64% in 2006, 2007 and 2008, respectively. After 36 months, retention was 50% and 41% for those enrolled in 2005 and 2006, respectively. The percentage virally suppressed remained similar at 6 months, 82% vs 84%, 84% and 85% from 2005, 2006, 2007 to 2008, respectively, p=0.66; but improved slightly at 12 months, 78% vs 83%, 83% and 84% from 2005 to 2008, p=0.05. At 36 months, it was 84% and 82% for the 2005 and 2006 cohorts, respectively. CONCLUSIONS: The results show that a well-managed private practitioner model can achieve comparable results to public services, although long-term retention needs further evaluation. This model of ART delivery can be used to expand access to ART in areas where the public sector is unable to meet the demand.

Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies.

BACKGROUND: The World Health Organization recommends the screening of all people living with HIV for tuberculosis (TB) disease, followed by TB treatment, or isoniazid preventive therapy (IPT) when TB is excluded. However, the difficulty of reliably excluding TB disease has severely limited TB screening and IPT uptake in resource-limited settings. We conducted an individual participant data meta-analysis of primary studies, aiming to identify a sensitive TB screening rule. METHODS AND FINDINGS: We identified 12 studies that had systematically collected sputum specimens regardless of signs or symptoms, at least one mycobacterial culture, clinical symptoms, and HIV and TB disease status. Bivariate random-effects meta-analysis and the hierarchical summary relative operating characteristic curves were used to evaluate the screening performance of all combinations of variables of interest. TB disease was diagnosed in 557 (5.8%) of 9,626 people living with HIV. The primary analysis included 8,148 people living with HIV who could be evaluated on five symptoms from nine of the 12 studies. The median age was 34 years. The best performing rule was the presence of any one of: current cough (any duration), fever, night sweats, or weight loss. The overall sensitivity of this rule was 78.9% (95% confidence interval [CI] 58.3%-90.9%) and specificity was 49.6% (95% CI 29.2%-70.1%). Its sensitivity increased to 90.1% (95% CI 76.3%-96.2%) among participants selected from clinical settings and to 88.0% (95% CI 76.1%-94.4%) among those who were not previously screened for TB. Negative predictive value was 97.7% (95% CI 97.4%-98.0%) and 90.0% (95% CI 88.6%-91.3%) at 5% and 20% prevalence of TB among people living with HIV, respectively. Abnormal chest radiographic findings increased the sensitivity of the rule by 11.7% (90.6% versus 78.9%) with a reduction of specificity by 10.7% (49.6% versus 38.9%). CONCLUSIONS: Absence of all of current cough, fever, night sweats, and weight loss can identify a subset of people living with HIV who have a very low probability of having TB disease. A simplified screening rule using any one of these symptoms can be used in resource-constrained settings to identify people living with HIV in need of further diagnostic assessment for TB. Use of this algorithm should result in earlier TB diagnosis and treatment, and should allow for substantial scale-up of IPT.

Barriers to implementation of isoniazid preventive therapy in HIV clinics: a qualitative study.

OBJECTIVES: Despite good evidence that isoniazid preventive therapy (IPT) reduces incidence of tuberculosis among people with HIV infection, implementation of IPT is low. This study aimed to describe barriers to IPT implementation from healthcare provider and patient perspectives in a donor-funded HIV care programme in Gauteng province, South Africa, in which IPT is recommended, but delivery is variable. DESIGN: A qualitative study using in-depth interviews and a focus group discussion. METHODS: We conducted interviews with 22 clinic staff and 20 patients from 10 purposively selected HIV clinics, and a staff focus group discussion. Staff were questioned on their knowledge and experience of IPT, and asked about barriers to its use. Patients were asked for their opinions about taking IPT. RESULTS: Healthcare workers reported the primary barrier to IPT use was lack of knowledge and experience. Prescribers were unaware of the benefits of IPT and unclear about guidelines. The belief that existing screening tools are inaccurate in HIV-infected individuals and the need to refer patients to separate clinics for tuberculosis screening also emerged as barriers. No patients had heard of IPT. CONCLUSION: Barriers to the widespread use of IPT primarily derived from healthcare workers, in particular, lack of experience among physicians. In addition to overcoming operational barriers, a change in healthcare worker perception is needed if IPT is to be widely used; we suggest local clinical opinion leaders could help achieve this.

Contrasting predictors of poor antiretroviral therapy outcomes in two South African HIV programmes: a cohort study.

BACKGROUND: Many national antiretroviral therapy (ART) programmes encourage providers to identify and address baseline factors associated with poor treatment outcomes, including modifiable adherence-related behaviours, before initiating ART. However, evidence on such predictors is scarce, and providers judgement may often be inaccurate. To help address this evidence gap, this observational cohort study examined baseline factors potentially predictive of poor treatment outcomes in two ART programmes in South Africa, with a particular focus on determinants of adherence. METHODS: Treatment-naïve patients starting ART were enrolled from a community and a workplace ART programme. Potential baseline predictors associated with poor treatment outcomes (defined as viral load > 400 copies/ml or having discontinued treatment by six months) were assessed using logistic regression. Exposure variables were organised for regression analysis using a hierarchical framework. RESULTS: 38/227 (17%) of participants in the community had poor treatment outcomes compared to 47/117 (40%) in the workplace. In the community, predictors of worse outcomes included: drinking more than 20 units of alcohol per week, having no prior experience of chronic medications, and consulting a traditional healer in the past year (adjusted odds ratio [aOR] 15.36, 95% CI 3.22-73.27; aOR 2.30, 95%CI 1.00-5.30; aOR 2.27, 95% CI 1.00-5.19 respectively). Being male and knowing someone on ART were associated with better outcomes (aOR 0.25, 95%CI 0.09-0.74; aOR 0.44, 95%CI 0.19-1.01 respectively). In the workplace, predictors of poor treatment outcomes included being uncertain about the health effects of ART and a traditional healer's ability to treat HIV (aOR 7.53, 95%CI 2.02-27.98; aOR 4.40, 95%CI 1.41-13.75 respectively). Longer pre-ART waiting time (2-12 weeks compared to <2 weeks) predicted better treatment outcomes (aOR 0.13, 95% CI 0.03-0.56). CONCLUSION: Baseline predictors of poor treatment outcomes were largely unique to each programme, likely reflecting different populations and pathways to HIV care. In the workplace, active promotion of HIV testing may have extended ART to individuals who, without provider initiation, would not have spontaneously sought care. As provider-initiated testing makes ART available to individuals less motivated to seek care, patients may need additional adherence support, especially addressing uncertainty about the health benefits of ART.

Early risk assessment for viral haemorrhagic fever: experience at the Hospital for Tropical Diseases, London, UK.

OBJECTIVES: To implement a policy of systematic screening for viral haemorrhagic fever (VHF) among travellers returning from African countries with fever, commencing at initial clinical contact. METHODS: A protocol based on UK Advisory Committee on Dangerous Pathogens guidance was developed collaboratively by medical, nursing and laboratory staff. Audit was carried out to quantify resource demands and effects on time to diagnose malaria, the main differential diagnosis. RESULTS: A protocol is now implemented for all patients presenting to HTD with fever, with clear guidelines for interaction with clinical and laboratory staff at each stage. The protocol required moderate amounts of clinical and laboratory staff time and resulted in some additional hospital admissions. The time to a diagnosis of malaria increased from a median of 90 (range 50-125) min in patients without VHF risk to a median of 140 (range 101-225) min (p=0.0025) in those assessed as at risk. CONCLUSIONS: Although all acute medical services need to have robust procedures for early detection of patients with serious transmissible conditions, few implement such a policy. Our protocol requires increased human and other resources but has no important impact on the rapidity of diagnosis of malaria, and is now embedded in local practice.