Translating Technical Support Into Country Action: The Role of the Interagency Task Team on the Prevention and Treatment of HIV Infection in Pregnant Women, Mothers, and Children in the Global Plan Era.

While the Interagency Task Team on the Prevention and Treatment of HIV Infection in Pregnant Women, Mothers, and Children (IATT) partnership existed before the Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive (Global Plan), its reconfiguration was critical to coordinating provision of technical assistance that positively influenced country decision-making and program performance. This article describes how the Global Plan anchored the work of the IATT and, in turn, how the IATT's technical assistance helped to accelerate achievement of the Global Plan targets and milestones. The technical assistance that will be discussed addressed a broad range of priority actions and milestones described in the Global Plan: (1) planning for and implementing Option B+; (2) strengthening monitoring and evaluation systems; (3) translating evidence into action and advocacy; and (4) promoting community engagement. This article also reviews the ongoing challenges and opportunities of providing technical assistance in a rapidly evolving environment that calls for ever more flexible and contextualized responses. The effectiveness of technical assistance facilitated by the IATT was defined by its timeliness, evidence base, and unique global perspective that built on the competencies of its partners and promoted synergies across program areas. Reaching the final goal of eliminating vertical transmission of HIV infection and achieving an AIDS-free generation in countries with the highest HIV burden requires that the IATT partnership and technical assistance remain responsive to country-specific needs while aligning with the current programmatic reality and new global goals such as the Sustainable Development Goals and 90-90-90 targets.

Implementation and Operational Research: Cost-Effectiveness of Antiretroviral Therapy and Isoniazid Prophylaxis to Reduce Tuberculosis and Death in People Living With HIV in Botswana.

OBJECTIVE: In Botswana, a 36-month course of isoniazid treatment of latent tuberculosis (TB) infection [isoniazid preventive therapy (IPT)] was superior to 6-month IPT in reducing TB and death in persons living with HIV (PLHIV), having positive tuberculin skin tests (TSTs) but not in those with negative TST. We examined the cost-effectiveness of IPT in Botswana, where antiretroviral therapy (ART) is widely available. DESIGN: Using a decision-analytic model, we determined the incremental cost-effectiveness of strategies for reducing TB and death in 10,000 PLHIV over 36 months. METHODS: IPT for 6 months and provision of ART if CD4 lymphocyte count <250 cells per microliter (2011 Botswana policy) was compared with 6 alternative strategies that varied the use of IPT, TST, and ART for CD4 count thresholds, including CD4 <350 and <500 cells per microliter. RESULTS: Botswana policy, 2011 was dominated by most other strategies. IPT of 36 months for TST-positive PLHIV with ART for CD4 <250 cells per microliter resulted in 120 fewer TB cases for an additional cost of $1612 per case averted and resulted in 80 fewer deaths for an additional $2418 per death averted compared with provision of 6-month IPT to TST-positive PLHIV who received ART for CD4 <250 cells per microliter, the next most effective strategy. Alternative strategies offered lower incremental effectiveness at higher cost. These findings remained consistent in sensitivity analyses. CONCLUSIONS: A strategy of treating PLHIV who have positive TST with 36-month IPT is more cost effective for reducing both TB and death compared with providing IPT without a TST, providing only 6-month IPT, or expanding ART eligibility without IPT.

Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models.

BACKGROUND: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per µL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. METHODS: We used several independent mathematical models in four settings-South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)-to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per µL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per µL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP. FINDINGS: In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per µL or less ranged from $237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per µL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to $749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost effective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to $241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per µL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost effective. INTERPRETATION: Our estimates suggest that earlier eligibility for antiretroviral therapy is very cost effective in low-income and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets. FUNDING: Bill & Melinda Gates Foundation, WHO.

The incremental cost of switching from Option B to Option B+ for the prevention of mother-to-child transmission of HIV.

OBJECTIVE: To estimate the incremental cost over 5 years of a policy switch from the Option B to the Option B+ protocol for the prevention of mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV). METHODS: Data from cost studies and other published sources were used to determine the cost, per woman and per cohort (1000 breastfeeding and 1000 non-breastfeeding women), of switching from Option B (maternal triple antiretroviral [ARV] regimen during pregnancy and breastfeeding plus daily nevirapine for the infant for 6 weeks) to Option B+ (maternal triple ARV regimen initiated during pregnancy and continued for life). The variables used to model the different scenarios were maternal CD4+ T lymphocyte (CD4+ cell) count (350-500 versus > 500 cells/µl), rate of decline in CD4+ cells (average, rapid, slow), breastfeeding status (yes, no) and breastfeeding duration (12, 18 or 24 months). FINDINGS: For women with CD4+ cell counts of 350-500 cells/µl, the incremental cost per 1000 women was 157,345 United States dollars (US$) for breastfeeding women and US$ 92,813 for non-breastfeeding women. For women with CD4+ cell counts > 500 cells/µl, the incremental cost per 1000 women ranged from US$ 363,443 to US$ 484,591 for breastfeeding women and was US$ 605,739 for non-breastfeeding women. CONCLUSION: From a cost perspective, a policy switch from Option B to Option B+ is feasible in PMTCT programme settings where resources are currently being allocated to Option B.

Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models.

BACKGROUND: New WHO guidelines recommend ART initiation for HIV-positive persons with CD4 cell counts ≤500 cells/µL, a higher threshold than was previously recommended. Country decision makers must consider whether to further expand ART eligibility accordingly. METHODS: We used multiple independent mathematical models in four settings-South Africa, Zambia, India, and Vietnam-to evaluate the potential health impact, costs, and cost-effectiveness of different adult ART eligibility criteria under scenarios of current and expanded treatment coverage, with results projected over 20 years. Analyses considered extending eligibility to include individuals with CD4 ≤500 cells/µL or all HIV-positive adults, compared to the previous recommendation of initiation with CD4 ≤350 cells/µL. We assessed costs from a health system perspective, and calculated the incremental cost per DALY averted ($/DALY) to compare competing strategies. Strategies were considered 'very cost-effective' if the $/DALY was less than the country's per capita gross domestic product (GDP; South Africa: $8040, Zambia: $1425, India: $1489, Vietnam: $1407) and 'cost-effective' if $/DALY was less than three times per capita GDP. FINDINGS: In South Africa, the cost per DALY averted of extending ART eligibility to CD4 ≤500 cells/µL ranged from $237 to $1691/DALY compared to 2010 guidelines; in Zambia, expanded eligibility ranged from improving health outcomes while reducing costs (i.e. dominating current guidelines) to $749/DALY. Results were similar in scenarios with substantially expanded treatment access and for expanding eligibility to all HIV-positive adults. Expanding treatment coverage in the general population was therefore found to be cost-effective. In India, eligibility for all HIV-positive persons ranged from $131 to $241/DALY and in Vietnam eligibility for CD4 ≤500 cells/µL cost $290/DALY. In concentrated epidemics, expanded access among key populations was also cost-effective. INTERPRETATION: Earlier ART eligibility is estimated to be very cost-effective in low- and middle-income settings, although these questions should be revisited as further information becomes available. Scaling-up ART should be considered among other high-priority health interventions competing for health budgets. FUNDING: The Bill and Melinda Gates Foundation and World Health Organization.

HIV treatment as prevention: issues in economic evaluation.

Meyer-Rath and Over assert in another article in the July 2012 PLoS Medicine Collection, "Investigating the Impact of Treatment on New HIV Infections", that economic evaluations of antiretroviral therapy (ART) in currently existing programs and in HIV treatment as prevention (TasP) programs should use cost functions that capture cost dependence on a number of factors, such as scale and scope of delivery, health states, ART regimens, health workers' experience, patients' time on treatment, and the distribution of delivery across public and private sectors. We argue that for particular evaluation purposes (e.g., to establish the social value of TasP) and from particular perspectives (e.g., national health policy makers) less detailed cost functions may be sufficient. We then extend the discussion of economic evaluation of TasP, describing why ART outcomes and costs assessed in currently existing programs are unlikely to be generalizable to TasP programs for several fundamental reasons. First, to achieve frequent, widespread HIV testing and high uptake of ART immediately following an HIV diagnosis, TasP programs will require components that are not present in current ART programs and whose costs are not included in current estimates. Second, the early initiation of ART under TasP will change not only patients' disease courses and treatment experiences--which can affect behaviors that determine clinical treatment success, such as ART adherence and retention--but also quality of life and economic outcomes for HIV-infected individuals. Third, the preventive effects of TasP are likely to alter the composition of the HIV-infected population over time, changing its biological and behavioral characteristics and leading to different costs and outcomes for ART.

PEPFAR's past and future efforts to cut costs, improve efficiency, and increase the impact of global HIV programs.

Amid the global economic crisis, the President's Emergency Plan for AIDS Relief (PEPFAR) and other organizations have been pressed to do more with constrained resources to meet unmet needs in the worldwide HIV/AIDS pandemic. PEPFAR has approached this challenge through the development of an Impact and Efficiency Acceleration Plan, which includes improving the collection and use of economic and financial data, increasing the efficiency of HIV/AIDS program implementation, and collaborating with governments and multilateral organizations to maximize the impact of the resources provided by the United States. For example, by linking financial data with program outputs, PEPFAR was able to help its implementing partners in Mozambique reduce mean unit expenditures for people receiving antiretroviral treatment by 45 percent, from $265 to $145 per person, between 2009 and 2011. This article describes the plan's elements, provides examples of progress and challenges to its implementation, and assesses the prospects for further improvements in efficiency and impact.

Cost-effectiveness of tuberculosis diagnostic strategies to reduce early mortality among persons with advanced HIV infection initiating antiretroviral therapy.

BACKGROUND: In sub-Saharan Africa, patients with advanced HIV experience high mortality during the first few months of antiretroviral therapy (ART), largely attributable to tuberculosis (TB). We evaluated the cost-effectiveness of TB diagnostic strategies to reduce this early mortality. METHODS: We developed a decision analytic model to estimate the incremental cost, deaths averted, and cost-effectiveness of 3 TB diagnostic algorithms. The model base case represents current practice (symptoms screening, sputum smear, and chest radiography) in many resource-limited countries in sub-Saharan Africa. We compared the current practice with World Health Organization (WHO)-recommended practice with culture and WHO-recommended practice with the Xpert mycobacterium tuberculosis and resistance to rifampicin test and considered relevant medical costs from a health system perspective using the timeframe of the first 6 months of ART. We conducted univariate and probabilistic sensitivity analyses on all parameters in the model. RESULTS: When considering TB diagnosis and treatment and ART costs, the cost per patient was $850 for current practice, $809 for the algorithm with Xpert test, and $879 for the algorithm with culture. Our results showed that both WHO-recommended algorithms avert more deaths among TB cases than does the current practice. The algorithm with Xpert test was least costly at reducing early mortality compared with the current practice. Sensitivity analyses indicated that cost-effectiveness findings were stable. CONCLUSIONS: Our analysis showed that culture or Xpert were cost-effective at reducing early mortality during the first 6 months of ART compared with the current practice. Thus, our findings provide support for ongoing efforts to expand TB diagnostic capacity.

Cost-effectiveness analysis of diagnostic options for pneumocystis pneumonia (PCP).

BACKGROUND: Diagnosis of Pneumocystis jirovecii pneumonia (PCP) is challenging, particularly in developing countries. Highly sensitive diagnostic methods are costly, while less expensive methods often lack sensitivity or specificity. Cost-effectiveness comparisons of the various diagnostic options have not been presented. METHODS AND FINDINGS: We compared cost-effectiveness, as measured by cost per life-years gained and proportion of patients successfully diagnosed and treated, of 33 PCP diagnostic options, involving combinations of specimen collection methods [oral washes, induced and expectorated sputum, and bronchoalveolar lavage (BAL)] and laboratory diagnostic procedures [various staining procedures or polymerase chain reactions (PCR)], or clinical diagnosis with chest x-ray alone. Our analyses were conducted from the perspective of the government payer among ambulatory, HIV-infected patients with symptoms of pneumonia presenting to HIV clinics and hospitals in South Africa. Costing data were obtained from the National Institutes of Communicable Diseases in South Africa. At 50% disease prevalence, diagnostic procedures involving expectorated sputum with any PCR method, or induced sputum with nested or real-time PCR, were all highly cost-effective, successfully treating 77-90% of patients at $26-51 per life-year gained. Procedures using BAL specimens were significantly more expensive without added benefit, successfully treating 68-90% of patients at costs of $189-232 per life-year gained. A relatively cost-effective diagnostic procedure that did not require PCR was Toluidine Blue O staining of induced sputum ($25 per life-year gained, successfully treating 68% of patients). Diagnosis using chest x-rays alone resulted in successful treatment of 77% of patients, though cost-effectiveness was reduced ($109 per life-year gained) compared with several molecular diagnostic options. CONCLUSIONS: For diagnosis of PCP, use of PCR technologies, when combined with less-invasive patient specimens such as expectorated or induced sputum, represent more cost-effective options than any diagnostic procedure using BAL, or chest x-ray alone.

Measles supplemental immunization activities improve measles vaccine coverage and equity: Evidence from Kenya, 2002.

OBJECTIVES: To compare the measles vaccine coverage achieved through the routine vaccination program with that achieved during the 2002 supplemental immunization activity (SIA) at the national and provincial level, the percentage of previously unvaccinated children (zero-dose children) reached during the SIA, and the equity of measles vaccine coverage among children aged 9-23 months in Kenya. METHODS: Using data from a post-SIA coverage survey conducted in Kenya, we compute routine and SIA measles vaccine coverage and the percent of zero-dose children vaccinated during the SIA at the national and provincial level. Nationwide and for each province, we use the concentration index (CI) to measure equity of measles vaccine coverage. RESULTS: The SIA improved both coverage and equity, achieving significantly higher coverage in all provinces with routine measles vaccination coverage less than 80%, reached a large percentage of zero-dose children in these provinces, and reached more children belonging to the poorest households. CONCLUSION: Overall, by improving both measles vaccine coverage and equity in Kenya, the 2002 SIA reduced the gap in immunity between rich and poor households. Measles SIAs provide an ideal platform for delivering other life-saving child health interventions.

The costs of future polio risk management policies.

Decisionmakers need information about the anticipated future costs of maintaining polio eradication as a function of the policy options under consideration. Given the large portfolio of options, we reviewed and synthesized the existing cost data relevant to current policies to provide context for future policies. We model the expected future costs of different strategies for continued vaccination, surveillance, and other costs that require significant potential resource commitments. We estimate the costs of different potential policy portfolios for low-, middle-, and high-income countries to demonstrate the variability in these costs. We estimate that a global transition from routine immunization with oral poliovirus vaccine (OPV) to inactivated poliovirus vaccine (IPV) would increase the costs of managing polio globally, although routine IPV use remains less costly than routine OPV use with supplemental immunization activities. The costs of surveillance and a stockpile, while small compared to routine vaccination costs, represent important expenditures to ensure adequate response to potential outbreaks. The uncertainty and sensitivity analyses highlight important uncertainty in the aggregated costs and demonstrates that the discount rate and uncertainty in price and administration cost of IPV drives the expected incremental cost of routine IPV vs. OPV immunization.

Global surveillance and the value of information: the case of the global polio laboratory network.

Effective control and eradication of diseases requires reliable information from surveillance activities, including laboratories, which typically incur real financial costs. This article presents data from a survey we conducted to estimate the costs of the Global Polio Laboratory Network (GPLN), which currently supports aggressive global surveillance for acute flaccid paralysis (AFP) to detect circulating polioviruses. The Global Polio Eradication Initiative (GPEI) of the World Health Organization (WHO) provides resources for some of the laboratory network costs, but the total cost of the network remains relatively poorly characterized given the limited documentation of national contributions. We surveyed network laboratories to quantify AFP surveillance support costs and provide data for cost estimates of potential posteradication surveillance policies related to the laboratories. We estimate that the GPLN currently requires millions (US dollars 2002) in total support annually, and that half of the support for national and regional reference laboratories comes from external donors through the WHO or bilateral agreements and half from within nations that host those laboratories. The article also presents the framework for considering the value of information from this global surveillance network and suggests that the expected value of surveillance information from the GPLN currently exceeds its costs. We also provided important insights about how the value of information may change after successful eradication of wild polioviruses.

Development and consideration of global policies for managing the future risks of poliovirus outbreaks: insights and lessons learned through modeling.

The success of the Global Polio Eradication Initiative promises to bring large benefits, including sustained improvements in quality of life (i.e., cases of paralytic disease and deaths avoided) and costs saved from cessation of vaccination. Obtaining and maintaining these benefits requires that policymakers manage the transition from the current massive use of oral poliovirus vaccine (OPV) to a world without OPV and free of the risks of potential future reintroductions of live polioviruses. This article describes the analytical journey that began in 2001 with a retrospective case study on polio risk management and led to development of dynamic integrated risk, economic, and decision analysis tools to inform global policies for managing the risks of polio. This analytical journey has provided several key insights and lessons learned that will be useful to future analysts involved in similar complex decision-making processes.

Factors affecting U.S. manufacturers' decisions to produce vaccines.

Recent supply interruptions of childhood vaccines have had negative impacts on U.S. public health policies and vaccine delivery. To understand how manufacturers perceive production incentives and disincentives, the Centers for Disease Control and Prevention (CDC) met with the four pharmaceutical firms that sold vaccines through CDC-negotiated contracts during 2002 and 2003. These meetings shed light on the regulatory burden, high costs of the delay between initial investment and sales, and higher costs of new technologies versus older vaccines. All four manufacturers are investing more in research and development because new technologies have advanced their ability to create vaccines not thought possible before.

Cost analysis of post-polio certification immunization policies.

OBJECTIVE: An analysis was conducted to estimate the costs of different potential post-polio certification immunization policies currently under consideration, with the objective of providing this information to policy-makers. METHODS: We analyzed three global policy options: continued use of oral poliovirus vaccine (OPV); OPV cessation with optional inactivated poliovirus vaccine (IPV); and OPV cessation with universal IPV. Assumptions were made on future immunization policy decisions taken by low-, middle-, and high-income countries. We estimated the financial costs of each immunization policy, the number of vaccine-associated paralytic poliomyelitis (VAPP) cases, and the global costs of maintaining an outbreak response capacity. The financial costs of each immunization policy were based on estimates of the cost of polio vaccine, its administration, and coverage projections. The costs of maintaining outbreak response capacity include those associated with developing and maintaining a vaccine stockpile in addition to laboratory and epidemiological surveillance. We used the period 2005-20 as the time frame for the analysis. FINDINGS: OPV cessation with optional IPV, at an estimated cost of US$ 20,412 million, was the least costly option. The global cost of outbreak response capacity was estimated to be US$ 1320 million during 2005-20. The policy option continued use of OPV resulted in the highest number of VAPP cases. OPV cessation with universal IPV had the highest financial costs, but it also had the least number of VAPP cases. Sensitivity analyses showed that global costs were sensitive to assumptions on the cost of the vaccine. Analysis also showed that if the price per dose of IPV was reduced to US$ 0.50 for low-income countries, the cost of OPV cessation with universal IPV would be the same as the costs of continued use of OPV. CONCLUSION: Projections on the vaccine price per dose and future coverage rates were major drivers of the global costs of post-certification polio immunization. The break-even price of switching to IPV compared with continuing with OPV immunizations is US$ 0.50 per dose of IPV. However, this doses not account for the cost of vaccine-derived poliovirus cases resulting from the continued use of OPV. In addition to financial costs, risk assessments related to the re-emergence of polio will be major determinants of policy decisions.

Cost-effectiveness of three different vaccination strategies against measles in Zambian children.

The vaccination program in Zambia includes one dose of measles vaccine at 9 months of age. The objective of this study was to compare the cost-effectiveness of the current one-dose measles vaccination program with an immunization schedule in which a second dose is provided either through routine health services or through supplemental immunization activities (SIAs). We simulated the expected cost and impact of the vaccination strategies for an annual cohort of 400,000 children, assuming 80% vaccination coverage in both routine and SIAs and an analytic horizon of 15 years. A vaccination program which includes SIAs reaching children not previously vaccinated would prevent on additional 29,242 measles cases and 1462 deaths for each vaccinated birth cohort when compared with a one-dose program. Given the parameters established for this analysis, such a program would be cost-saving and the most cost-effective vaccination strategy for Zambia.

Policy decision options during the first 5 years following certification of polio eradication.

Policy makers face a number of difficult choices as they develop policies to ensure maintenance of a polio-free world following global eradication and certification. These policy decisions include choices about immunization, outbreak response (including whether to create a vaccine stockpile), surveillance, containment, management of chronic excretors, and investment in future research. This paper focuses on identifying the categories of decisions and characterizing the actual factors that country-level policy makers must weigh to manage polio risks during the first 5 years after certification. Building on a comprehensive literature review, we report the results of the first qualitative analysis to: (1) systematically characterize each type of decision and the relevant options during the first 5 years after certification, (2) clearly identify critical factors that influence the choices, and (3) specifically demonstrate the interdependence among the decisions to produce a reduced set of decision options. This paper explicitly focuses on the different perspectives of developed and developing countries in characterizing the options. While the management of polio risk in the postcertification period presents important challenges, this comprehensive approach helps simplify the process by focusing on critical decisions.