Pediatric Respiratory Syncytial Virus Diagnostic Testing Performance: A Systematic Review and Meta-analysis.

BACKGROUND: Adding additional specimen types (eg, serology or sputum) to nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) increases respiratory syncytial virus (RSV) detection among adults. We assessed if a similar increase occurs in children and quantified underascertainment associated with diagnostic testing. METHODS: We searched databases for studies involving RSV detection in persons <18 years using ≥2 specimen types or tests. We assessed study quality using a validated checklist. We pooled detection rates by specimen and diagnostic tests and quantified performance. RESULTS: We included 157 studies. Added testing of additional specimens to NP aspirate (NPA), NPS, and/or nasal swab (NS) RT-PCR resulted in statistically nonsignificant increases in RSV detection. Adding paired serology testing increased RSV detection by 10%, NS by 8%, oropharyngeal swabs by 5%, and NPS by 1%. Compared to RT-PCR, direct fluorescence antibody tests, viral culture, and rapid antigen tests were 87%, 76%, and 74% sensitive, respectively (pooled specificities all ≥98%). Pooled sensitivity of multiplex versus singleplex RT-PCR was 96%. CONCLUSIONS: RT-PCR was the most sensitive pediatric RSV diagnostic test. Adding multiple specimens did not substantially increase RSV detection, but even small proportional increases could result in meaningful changes in burden estimates. The synergistic effect of adding multiple specimens should be evaluated.

Underascertainment of Respiratory Syncytial Virus Infection in Adults Due to Diagnostic Testing Limitations: A Systematic Literature Review and Meta-analysis.

BACKGROUND: Most observational population-based studies identify respiratory syncytial virus (RSV) by nasal/nasopharyngeal swab reverse transcriptase real-time PCR (RT-PCR) only. We conducted a systematic review and meta-analyses to quantify specimen and diagnostic testing-based underascertainment of adult RSV infection. METHODS: EMBASE, PubMed, and Web of Science were searched (January 2000-December 2021) for studies including adults using/comparing >1 RSV testing approach. We quantified test performance and RSV detection increase associated with using multiple specimen types. RESULTS: Among 8066 references identified, 154 met inclusion. Compared to RT-PCR, other methods were less sensitive: rapid antigen detection test (RADT; pooled sensitivity, 64%), direct fluorescent antibody (DFA; 83%), and viral culture (86%). Compared to singleplex PCR, multiplex PCR's sensitivity was lower (93%). Compared to nasal/nasopharyngeal swab RT-PCR alone, adding another specimen type increased detection: sputum RT-PCR, 52%; 4-fold rise in paired serology, 44%; and oropharyngeal swab RT-PCR, 28%. Sensitivity was lower in estimates limited to only adults (for RADT, DFA, and viral culture), and detection rate increases were largely comparable. CONCLUSIONS: RT-PCR, particularly singleplex testing, is the most sensitive RSV diagnostic test in adults. Adding additional specimen types to nasopharyngeal swab RT-PCR testing increased RSV detection. Synergistic effects of using ≥3 specimen types should be assessed, as this approach may improve the accuracy of adult RSV burden estimates.

Respiratory syncytial virus (RSV) is an important cause of illness and death among older adults. Most studies of how frequent RSV infection is among older adults use only nasal swab testing to identify RSV infection. These nasal swabs are checked for genetic material from the virus, known as polymerase chain reaction (PCR) testing. We examined published studies from January 2000 to December 2021 to estimate how many RSV infections would be missed by using only this approach to RSV testing. We found 154 studies had information to answer our question. Compared to PCR testing of nasal swab alone, adding sputum specimen PCR testing (ie, testing cough mucus or phlegm for RSV genetic material) increased RSV infections found by 52%. Adding blood testing increased RSV infections found by 44%. Adding mouth/throat swab PCR testing, increased RSV infections by 28%. In summary, adding additional specimen types to nasal swab PCR testing increased RSV detection. Impact of using 3 or more specimen types at the same time should be assessed, as this approach may further improve accuracy.

Cost-effectiveness of bedaquiline, pretomanid and linezolid for treatment of extensively drug-resistant tuberculosis in South Africa, Georgia and the Philippines.

OBJECTIVES: Patients with highly resistant tuberculosis have few treatment options. Bedaquiline, pretomanid and linezolid regimen (BPaL) is a new regimen shown to have favourable outcomes after six months. We present an economic evaluation of introducing BPaL against the extensively drug-resistant tuberculosis (XDR-TB) standard of care in three epidemiological settings. DESIGN: Cost-effectiveness analysis using Markov cohort model. SETTING: South Africa, Georgia and the Philippines. PARTICIPANTS: XDR-TB and multidrug-resistant tuberculosis (MDR-TB) failure and treatment intolerant patients. INTERVENTIONS: BPaL regimen. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) Incremental cost per disability-adjusted life years averted by using BPaL against standard of care at the Global Drug Facility list price. (2) The potential maximum price at which the BPaL regimen could become cost neutral. RESULTS: BPaL for XDR-TB is likely to be cost saving in all study settings when pretomanid is priced at the Global Drug Facility list price. The magnitude of these savings depends on the prevalence of XDR-TB in the country and can amount, over 5 years, to approximately US$ 3 million in South Africa, US$ 200 000 and US$ 60 000 in Georgia and the Philippines, respectively. In South Africa, related future costs of antiretroviral treatment (ART) due to survival of more patients following treatment with BPaL reduced the magnitude of expected savings to approximately US$ 1 million. Overall, when BPaL is introduced to a wider population, including MDR-TB treatment failure and treatment intolerant, we observe increased savings and clinical benefits. The potential threshold price at which the probability of the introduction of BPaL becoming cost neutral begins to increase is higher in Georgia and the Philippines (US$ 3650 and US$ 3800, respectively) compared with South Africa (US$ 500) including ART costs. CONCLUSIONS: Our results estimate that BPaL can be a cost-saving addition to the local TB programmes in varied programmatic settings.

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.

Integrated TB and HIV care for Mozambican children: temporal trends, site-level determinants of performance, and recommendations for improved TB preventive treatment.

BACKGROUND: Pediatric tuberculosis (TB), human immunodeficiency virus (HIV), and TB-HIV co-infection are health problems with evidence-based diagnostic and treatment algorithms that can reduce morbidity and mortality. Implementation and operational barriers affect adherence to guidelines in many resource-constrained settings, negatively affecting patient outcomes. This study aimed to assess performance in the pediatric HIV and TB care cascades in Mozambique. METHODS: A retrospective analysis of routine PEPFAR site-level HIV and TB data from 2012 to 2016 was performed. Patients 0-14 years of age were included. Descriptive statistics were used to report trends in TB and HIV indicators. Linear regression was done to assess associations of site-level variables with performance in the pediatric TB and HIV care cascades using 2016 data. RESULTS: Routine HIV testing and cotrimoxazole initiation for co-infected children in the TB program were nearly optimal at 99% and 96% in 2016, respectively. Antiretroviral therapy (ART) initiation was lower at 87%, but steadily improved from 2012 to 2016. From the HIV program, TB screening at the last consultation rose steadily over the study period, reaching 82% in 2016. The percentage of newly enrolled children who received either TB treatment or isoniazid preventive treatment (IPT) also steadily improved in all provinces, but in 2016 was only at 42% nationally. Larger volume sites were significantly more likely to complete the pediatric HIV and TB care cascades in 2016 (p value range 0.05 to < 0.001). CONCLUSIONS: Mozambique has made significant strides in improving the pediatric care cascades for children with TB and HIV, but there were missed opportunities for TB diagnosis and prevention, with IPT utilization being particularly problematic. Strengthened TB/HIV programming that continues to focus on pediatric ART scale-up while improving delivery of TB preventive therapy, either with IPT or newer rifapentine-based regimens for age-eligible children, is needed.

A Systematic Review of Methodological Variation in Healthcare Provider Perspective Tuberculosis Costing Papers Conducted in Low- and Middle-Income Settings, Using An Intervention-Standardised Unit Cost Typology.

BACKGROUND: There is a need for easily accessible tuberculosis unit cost data, as well as an understanding of the variability of methods used and reporting standards of that data. OBJECTIVE: The aim of this systematic review was to descriptively review papers reporting tuberculosis unit costs from a healthcare provider perspective looking at methodological variation; to assess quality using a study quality rating system and machine learning to investigate the indicators of reporting quality; and to identify the data gaps to inform standardised tuberculosis unit cost collection and consistent principles for reporting going forward. METHODS: We searched grey and published literature in five sources and eight databases, respectively, using search terms linked to cost, tuberculosis and tuberculosis health services including tuberculosis treatment and prevention. For inclusion, the papers needed to contain empirical unit cost estimates for tuberculosis interventions from low- and middle-income countries, with reference years between 1990 and 2018. A total of 21,691 papers were found and screened in a phased manner. Data were extracted from the eligible papers into a detailed Microsoft Excel tool, extensively cleaned and analysed with R software (R Project, Vienna, Austria) using the user interface of RStudio. A study quality rating was applied to the reviewed papers based on the inclusion or omission of a selection of variables and their relative importance. Following this, machine learning using a recursive partitioning method was utilised to construct a classification tree to assess the reporting quality. RESULTS: This systematic review included 103 provider perspective papers with 627 unit costs (costs not presented here) for tuberculosis interventions among a total of 140 variables. The interventions covered were active, passive and intensified case finding; tuberculosis treatment; above-service costs; and tuberculosis prevention. Passive case finding is the detection of tuberculosis cases where individuals self-identify at health facilities; active case finding is detection of cases of those not in health facilities, such as through outreach; and intensified case finding is detection of cases in high-risk populations. There was heterogeneity in some of the reported methods used such cost allocation, amortisation and the use of top-down, bottom-up or mixed approaches to the costing. Uncertainty checking through sensitivity analysis was only reported on by half of the papers (54%), while purposive and convenience sampling was reported by 72% of papers. Machine learning indicated that reporting on 'Intervention' (in particular), 'Urbanicity' and 'Site Sampling', were the most likely indicators of quality of reporting. The largest data gap identified was for tuberculosis vaccination cost data, the Bacillus Calmette-Guérin (BCG) vaccine in particular. There is a gap in available unit costs for 12 of 30 high tuberculosis burden countries, as well as for the interventions of above-service costs, tuberculosis prevention, and active and intensified case finding. CONCLUSION: Variability in the methods and reporting used makes comparison difficult and makes it hard for decision makers to know which unit costs they can trust. The study quality rating system used in this review as well as the classification tree enable focus on specific reporting aspects that should improve variability and increase confidence in unit costs. Researchers should endeavour to be explicit and transparent in how they cost interventions following the principles as laid out in the Global Health Cost Consortium's Reference Case for Estimating the Costs of Global Health Services and Interventions, which in turn will lead to repeatability, comparability and enhanced learning from others.

Correction to: A Systematic Review of Methodological Variation in Healthcare Provider Perspective Tuberculosis Costing Papers Conducted in Low- and Middle-Income Settings, Using An Intervention-Standardised Unit Cost Typology.

In the original version of this article, Fig. 3 was published in an incorrect format. The correct figure is published with this correction.

Examining Approaches to Estimate the Prevalence of Catastrophic Costs Due to Tuberculosis from Small-Scale Studies in South Africa.

BACKGROUND AND OBJECTIVE: In context of the End TB goal of zero tuberculosis (TB)-affected households encountering catastrophic costs due to TB by 2020, the estimation of national prevalence of catastrophic costs due to TB is a priority to inform programme design. We explore approaches to estimate the national prevalence of catastrophic costs due to TB from existing datasets as an alternative to nationally representative surveys. METHODS: We obtained, standardized and merged three patient-level datasets from existing studies on patient-incurred costs due to TB in South Africa. A deterministic cohort model was developed with the aim of estimating the national prevalence of catastrophic costs, using national data on the prevalence of TB and likelihood of loss to follow-up by income quintile and HIV status. Two approaches were tested to parameterize the model with existing cost data. First, a meta-analysis summarized study-level data by HIV status and income quintile. Second, a regression analysis of patient-level data also included employment status, education level and urbanicity. We summarized findings by type of cost and examined uncertainty around resulting estimates. RESULTS: Overall, the median prevalence of catastrophic costs for the meta-analysis and regression approaches were 11% (interquartile range [IQR] 9-13%) and 6% (IQR 5-8%), respectively. Both approaches indicated that the main burden of catastrophic costs falls on the poorest households. An individual-level regression analysis produced lower uncertainty around estimates than a study-level meta-analysis. CONCLUSIONS: This paper presents a novel application of existing data to estimate the national prevalence of catastrophic costs due to TB. This type of model could be useful for researchers and policy makers looking to inform certain policy decisions; however, some uncertainties remain due to limitations in data availability. There is an urgent need for standardized reporting of cost data and improved guidance on methods to collect income data to improve these estimates going forward.

Developing the Global Health Cost Consortium Unit Cost Study Repository for HIV and TB: methodology and lessons learned.

Consistently defined, accurate, and easily accessible cost data are a valuable resource to inform efficiency analyses, budget preparation, and sustainability planning in global health. The Global Health Cost Consortium (GHCC) designed the Unit Cost Study Repository (UCSR) to be a resource for standardised HIV and TB intervention cost data displayed by key characteristics such as intervention type, country, and target population. To develop the UCSR, the GHCC defined a typology of interventions for each disease; aligned interventions according to the standardised principles, methods, and cost and activity categories from the GHCC Reference Case for Estimating the Costs of Global Health Services and Interventions; completed a systematic literature review; conducted extensive data extraction; performed quality assurance; grappled with complex methodological issues such as the proper approach to the inflation and conversion of costs; developed and implemented a study quality rating system; and designed a web-based user interface that flexibly displays large amounts of data in a user-friendly way. Key lessons learned from the extraction process include the importance of assessing the multiple uses of extracted data; the critical role of standardising definitions (particularly units of measurement); using appropriate classifications of interventions and components of costs; the efficiency derived from programming data checks; and the necessity of extraction quality monitoring by senior analysts. For the web interface, lessons were: understanding the target audiences, including consulting them regarding critical characteristics; designing the display of data in "levels"; and incorporating alert and unique trait descriptions to further clarify differences in the data.

Impact of integration of sexual and reproductive health services on consultation duration times: results from the Integra Initiative.

The lack of human resources is a key challenge in scaling up of HIV services in Africa's health care system. Integrating HIV services could potentially increase their effectiveness and optimize the use of limited resources and clinical staff time. We examined the impact of integration of provider initiated HIV counselling and testing (PITC) and family planning (FP counselling and FP provision) services on duration of consultation to assess the impact of PITC and FP integration on staff workload. This study was conducted in 24 health facilities in Kenya under the Integra Initiative, a non-randomized, pre/post intervention trial to evaluate the impact of integrated HIV and sexual and reproductive health services on health and service outcomes. We compared the time spent providing PITC-only services, FP-only services and integrated PITC/FP services. We used log-linear regression to assess the impact of plausible determinants on the duration of clients' consultation times. Median consultation duration times were highest for PITC-only services (30 min), followed by integrated services (10 min) and FP-only services (8 min). Times for PITC-only and FP-only services were 69.7% higher (95% Confidence Intervals (CIs) 35.8-112.0) and 43.9% lower (95% CIs -55.4 to - 29.6) than times spent on these services when delivered as an integrated service, respectively. The reduction in consultation times with integration suggests a potential reduction in workload. The higher consultation time for PITC-only could be because more pre- and post-counselling is provided at these stand-alone services. In integrated PITC/FP services, the duration of the visit fell below that required by HIV testing guidelines, and service mix between counselling and testing substantially changed. Integration of HIV with FP services may compromise the quality of services delivered and care must be taken to clearly specify and monitor appropriate consultation duration times and procedures during the process of integrating HIV and FP services.

Cost-effectiveness of Xpert MTB/RIF for tuberculosis diagnosis in South Africa: a real-world cost analysis and economic evaluation.

BACKGROUND: In 2010 a new diagnostic test for tuberculosis, Xpert MTB/RIF, received a conditional programmatic recommendation from WHO. Several model-based economic evaluations predicted that Xpert would be cost-effective across sub-Saharan Africa. We investigated the cost-effectiveness of Xpert in the real world during national roll-out in South Africa. METHODS: For this real-world cost analysis and economic evaluation, we applied extensive primary cost and patient event data from the XTEND study, a pragmatic trial examining Xpert introduction for people investigated for tuberculosis in 40 primary health facilities (20 clusters) in South Africa enrolled between June 8, and Nov 16, 2012, to estimate the costs and cost per disability-adjusted life-year averted of introducing Xpert as the initial diagnostic test for tuberculosis, compared with sputum smear microscopy (the standard of care). FINDINGS: The mean total cost per study participant for tuberculosis investigation and treatment was US$312·58 (95% CI 252·46-372·70) in the Xpert group and $298·58 (246·35-350·82) in the microscopy group. The mean health service (provider) cost per study participant was $168·79 (149·16-188·42) for the Xpert group and $160·46 (143·24-177·68) for the microscopy group of the study. Considering uncertainty in both cost and effect using a wide range of willingness to pay thresholds, we found less than 3% probability that Xpert introduction improved the cost-effectiveness of tuberculosis diagnostics. INTERPRETATION: After analysing extensive primary data collection during roll-out, we found that Xpert introduction in South Africa was cost-neutral, but found no evidence that Xpert improved the cost-effectiveness of tuberculosis diagnosis. Our study highlights the importance of considering implementation constraints, when predicting and evaluating the cost-effectiveness of new tuberculosis diagnostics in South Africa. FUNDING: Bill & Melinda Gates Foundation.

Financing the HIV response in sub-Saharan Africa from domestic sources: Moving beyond a normative approach.

Despite optimism about the end of AIDS, the HIV response requires sustained financing into the future. Given flat-lining international aid, countries' willingness and ability to shoulder this responsibility will be central to access to HIV care. This paper examines the potential to expand public HIV financing, and the extent to which governments have been utilising these options. We develop and compare a normative and empirical approach. First, with data from the 14 most HIV-affected countries in sub-Saharan Africa, we estimate the potential increase in public HIV financing from economic growth, increased general revenue generation, greater health and HIV prioritisation, as well as from more unconventional and innovative sources, including borrowing, health-earmarked resources, efficiency gains, and complementary non-HIV investments. We then adopt a novel empirical approach to explore which options are most likely to translate into tangible public financing, based on cross-sectional econometric analyses of 92 low and middle-income country governments' most recent HIV expenditure between 2008 and 2012. If all fiscal sources were simultaneously leveraged in the next five years, public HIV spending in these 14 countries could increase from US$3.04 to US$10.84 billion per year. This could cover resource requirements in South Africa, Botswana, Namibia, Kenya, Nigeria, Ethiopia, and Swaziland, but not even half the requirements in the remaining countries. Our empirical results suggest that, in reality, even less fiscal space could be created (a reduction by over half) and only from more conventional sources. International financing may also crowd in public financing. Most HIV-affected lower-income countries in sub-Saharan Africa will not be able to generate sufficient public resources for HIV in the medium-term, even if they take very bold measures. Considerable international financing will be required for years to come. HIV funders will need to engage with broader health and development financing to improve government revenue-raising and efficiencies.

Cost-Effectiveness of Introducing the SILCS Diaphragm in South Africa.

BACKGROUND: Though South Africa has high contraceptive use, unintended pregnancies are still widespread. The SILCS diaphragm could reduce the number of women with unmet need by introducing a discreet, woman-initiated, non-hormonal barrier method to the contraceptive method mix. METHODS: A decision model was built to estimate the impact and cost-effectiveness of the introduction of the SILCS diaphragm in Gauteng among women with unmet need for contraception in terms of unintended and mistimed pregnancies averted, assuming that the available contraceptives on the market were not a satisfying option for those women. Full costs were estimated both from a provider's and user's perspective, which also accounts for women's travel and opportunity cost of time, assuming a 5% uptake among women with unmet contraceptive need. The incremental cost-effectiveness ratio is computed at five and 10 years after introduction to allow for a distribution of fixed costs over time. A probabilistic sensitivity analysis was conducted to incorporate decision uncertainty. RESULTS: The introduction of the SILCS diaphragm in Gauteng could prevent an estimated 8,365 unintended pregnancies and 2,117 abortions over five years, at an annual estimated cost of US$55 per woman. This comes to a cost per pregnancy averted of US$153 and US$171 from a user's and provider's perspectives, respectively, with slightly lower unit costs at 10 years. Major cost drivers will be the price of the SILCS diaphragm and the contraceptive gel, given their large contribution to total costs (around 60%). CONCLUSIONS: The introduction of the SILCS diaphragm in the public sector is likely to provide protection for some women for whom current contraceptive technologies are not an option. However to realize its potential, targeting will be needed to reach women with unmet need and those with likely high adherence. Further analyses are needed among potential users to optimize the introduction strategy.

The cost and cost-effectiveness of gender-responsive interventions for HIV: a systematic review.

INTRODUCTION: Harmful gender norms and inequalities, including gender-based violence, are important structural barriers to effective HIV programming. We assess current evidence on what forms of gender-responsive intervention may enhance the effectiveness of basic HIV programmes and be cost-effective. METHODS: Effective intervention models were identified from an existing evidence review ("what works for women"). Based on this, we conducted a systematic review of published and grey literature on the costs and cost-effectiveness of each intervention identified. Where possible, we compared incremental costs and effects. RESULTS: Our effectiveness search identified 36 publications, reporting on the effectiveness of 22 HIV interventions with a gender focus. Of these, 11 types of interventions had a corresponding/comparable costing or cost-effectiveness study. The findings suggest that couple counselling for the prevention of vertical transmission; gender empowerment, community mobilization, and female condom promotion for female sex workers; expanded female condom distribution for the general population; and post-exposure HIV prophylaxis for rape survivors are cost-effective HIV interventions. Cash transfers for schoolgirls and school support for orphan girls may also be cost-effective in generalized epidemic settings. CONCLUSIONS: There has been limited research to assess the cost-effectiveness of interventions that seek to address women's needs and transform harmful gender norms. Our review identified several promising, cost-effective interventions that merit consideration as critical enablers in HIV investment approaches, as well as highlight that broader gender and development interventions can have positive HIV impacts. By no means an exhaustive package, these represent a first set of interventions to be included in the investment framework.

Is there scope for cost savings and efficiency gains in HIV services? A systematic review of the evidence from low- and middle-income countries.

OBJECTIVE: To synthesize the data available--on costs, efficiency and economies of scale and scope--for the six basic programmes of the UNAIDS Strategic Investment Framework, to inform those planning the scale-up of human immunodeficiency virus (HIV) services in low- and middle-income countries. METHODS: The relevant peer-reviewed and "grey" literature from low- and middle-income countries was systematically reviewed. Search and analysis followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. FINDINGS: Of the 82 empirical costing and efficiency studies identified, nine provided data on economies of scale. Scale explained much of the variation in the costs of several HIV services, particularly those of targeted HIV prevention for key populations and HIV testing and treatment. There is some evidence of economies of scope from integrating HIV counselling and testing services with several other services. Cost efficiency may also be improved by reducing input prices, task shifting and improving client adherence. CONCLUSION: HIV programmes need to optimize the scale of service provision to achieve efficiency. Interventions that may enhance the potential for economies of scale include intensifying demand-creation activities, reducing the costs for service users, expanding existing programmes rather than creating new structures, and reducing attrition of existing service users. Models for integrated service delivery--which is, potentially, more efficient than the implementation of stand-alone services--should be investigated further. Further experimental evidence is required to understand how to best achieve efficiency gains in HIV programmes and assess the cost-effectiveness of each service-delivery model.