Prevention of Mother-To-Child Transmission of HIV: Cost-Effectiveness of Antiretroviral Regimens and Feeding Options in Rwanda

Background

Rwanda''s National PMTCT program aims to achieve elimination of new HIV infections in children by 2015. In November 2010, Rwanda adopted the WHO 2010 ARV guidelines for PMTCT recommending Option B (HAART) for all HIV-positive pregnant women extended throughout breastfeeding and discontinued (short course-HAART) only for those not eligible for life treatment. The current study aims to assess the cost-effectiveness of this policy choice.

Methods

Based on a cohort of HIV-infected pregnant women in Rwanda, we modelled the cost-effectiveness of six regimens: dual ARV prophylaxis with either 12 months breastfeeding or replacement feeding; short course HAART (Sc-HAART) prophylaxis with either 6 months breastfeeding, 12 months breastfeeding, or 18 months breastfeeding; and Sc-HAART prophylaxis with replacement feeding. Direct costs were modelled based on all inputs in each scenario and related unit costs. Effectiveness was evaluated by measuring HIV-free survival at 18 months. Savings correspond to the lifetime costs of HIV treatment and care avoided as a result of all vertical HIV infections averted.

Results

All PMTCT scenarios considered are cost saving compared to “no intervention.” Sc-HAART with 12 months breastfeeding or 6 months breastfeeding dominate all other scenarios. Sc-HAART with 12 months breastfeeding allows for more children to be alive and HIV-uninfected by 18 months than Sc-HAART with 6 months breastfeeding for an incremental cost per child alive and uninfected of 11,882 USD. This conclusion is sensitive to changes in the relative risk of mortality by 18 months for exposed HIV-uninfected children on replacement feeding from birth and those who were breastfed for only 6 months compared to those breastfeeding for 12 months or more.

Conclusion

Our findings support the earlier decision by Rwanda to adopt WHO Option B and could inform alternatives for breastfeeding duration. Local contexts and existing care delivery models should be part of national policy decisions.     

Taking ART to Scale: Determinants of the Cost and Cost-Effectiveness of Antiretroviral Therapy in 45 Clinical Sites in Zambia

Background

We estimated the unit costs and cost-effectiveness of a government ART program in 45 sites in Zambia supported by the Centre for Infectious Disease Research Zambia (CIDRZ).

Methods

We estimated per person-year costs at the facility level, and support costs incurred above the facility level and used multiple regression to estimate variation in these costs. To estimate ART effectiveness, we compared mortality in this Zambian population to that of a cohort of rural Ugandan HIV patients receiving co-trimoxazole (CTX) prophylaxis. We used micro-costing techniques to estimate incremental unit costs, and calculated cost-effectiveness ratios with a computer model which projected results to 10 years.

Results

The program cost $69.7 million for 125,436 person-years of ART, or $556 per ART-year. Compared to CTX prophylaxis alone, the program averted 33.3 deaths or 244.5 disability adjusted life-years (DALYs) per 100 person-years of ART. In the base-case analysis, the net cost per DALY averted was $833 compared to CTX alone. More than two-thirds of the variation in average incremental total and on-site cost per patient-year of treatment is explained by eight determinants, including the complexity of the patient-case load, the degree of adherence among the patients, and institutional characteristics including, experience, scale, scope, setting and sector.

Conclusions and Significance

The 45 sites exhibited substantial variation in unit costs and cost-effectiveness and are in the mid-range of cost-effectiveness when compared to other ART programs studied in southern Africa. Early treatment initiation, large scale, and hospital setting, are associated with statistically significantly lower costs, while others (rural location, private sector) are associated with shifting cost from on- to off-site. This study shows that ART programs can be significantly less costly or more cost-effective when they exploit economies of scale and scope, and initiate patients at higher CD4 counts.     

Cost-Effectiveness Analysis of Combination Therapies for Visceral Leishmaniasis in the Indian Subcontinent

Background

Visceral leishmaniasis is a systemic parasitic disease that is fatal unless treated. We assessed the cost and cost-effectiveness of alternative strategies for the treatment of visceral leishmaniasis in the Indian subcontinent. In particular we examined whether combination therapies are a cost-effective alternative compared to monotherapies.

Methods and Findings

We assessed the cost-effectiveness of all possible mono- and combination therapies for the treatment of visceral leishmaniasis in the Indian subcontinent (India, Nepal and Bangladesh) from a societal perspective using a decision analytical model based on a decision tree. Primary data collected in each country was combined with data from the literature and an expert poll (Delphi method). The cost per patient treated and average and incremental cost-effectiveness ratios expressed as cost per death averted were calculated. Extensive sensitivity analysis was done to evaluate the robustness of our estimations and conclusions. With a cost of US$92 per death averted, the combination miltefosine-paromomycin was the most cost-effective treatment strategy. The next best alternative was a combination of liposomal amphotericin B with paromomycin with an incremental cost-effectiveness of $652 per death averted. All other strategies were dominated with the exception of a single dose of 10mg per kg of liposomal amphotericin B. While strategies based on liposomal amphotericin B (AmBisome) were found to be the most effective, its current drug cost of US$20 per vial resulted in a higher average cost-effectiveness. Sensitivity analysis showed the conclusion to be robust to variations in the input parameters over their plausible range.

Conclusions

Combination treatments are a cost-effective alternative to current monotherapy for VL. Given their expected impact on the emergence of drug resistance, a switch to combination therapy should be considered once final results from clinical trials are available.     

Integrated HIV testing, malaria, and diarrhea prevention campaign in Kenya: modeled health impact and cost-effectiveness

Background

Efficiently delivered interventions to reduce HIV, malaria, and diarrhea are essential to accelerating global health efforts. A 2008 community integrated prevention campaign in Western Province, Kenya, reached 47,000 individuals over 7 days, providing HIV testing and counseling, water filters, insecticide-treated bed nets, condoms, and for HIV-infected individuals cotrimoxazole prophylaxis and referral for ongoing care. We modeled the potential cost-effectiveness of a scaled-up integrated prevention campaign.

Methods

We estimated averted deaths and disability-adjusted life years (DALYs) based on published data on baseline mortality and morbidity and on the protective effect of interventions, including antiretroviral therapy. We incorporate a previously estimated scaled-up campaign cost. We used published costs of medical care to estimate savings from averted illness (for all three diseases) and the added costs of initiating treatment earlier in the course of HIV disease.

Results

Per 1000 participants, projected reductions in cases of diarrhea, malaria, and HIV infection avert an estimated 16.3 deaths, 359 DALYs and $85,113 in medical care costs. Earlier care for HIV-infected persons adds an estimated 82 DALYs averted (to a total of 442), at a cost of $37,097 (reducing total averted costs to $48,015). Accounting for the estimated campaign cost of $32,000, the campaign saves an estimated $16,015 per 1000 participants. In multivariate sensitivity analyses, 83% of simulations result in net savings, and 93% in a cost per DALY averted of less than $20.

Discussion

A mass, rapidly implemented campaign for HIV testing, safe water, and malaria control appears economically attractive.     

Potential cost-effectiveness of universal access to modern contraceptives in Uganda

Background

Over two thirds of women who need contraception in Uganda lack access to modern effective methods. This study was conducted to estimate the potential cost-effectiveness of achieving universal access to modern contraceptives in Uganda by implementing a hypothetical new contraceptive program (NCP) from both societal and governmental (Ministry of Health (MoH)) perspectives.

Methodology/Principal Findings

A Markov model was developed to compare the NCP to the status quo or current contraceptive program (CCP). The model followed a hypothetical cohort of 15-year old girls over a lifetime horizon. Data were obtained from the Uganda National Demographic and Health Survey and from published and unpublished sources. Costs, life expectancy, disability-adjusted life expectancy, pregnancies, fertility and incremental cost-effectiveness measured as cost per life-year (LY) gained, cost per disability-adjusted life-year (DALY) averted, cost per pregnancy averted and cost per unit of fertility reduction were calculated. Univariate and probabilistic sensitivity analyses were performed to examine the robustness of results. Mean discounted life expectancy and disability-adjusted life expectancy (DALE) were higher under the NCP vs. CCP (28.74 vs. 28.65 years and 27.38 vs. 27.01 respectively). Mean pregnancies and live births per woman were lower under the NCP (9.51 vs. 7.90 and 6.92 vs. 5.79 respectively). Mean lifetime societal costs per woman were lower for the NCP from the societal perspective ($1,949 vs. $1,987) and the MoH perspective ($636 vs. $685). In the incremental analysis, the NCP dominated the CCP, i.e. it was both less costly and more effective. The results were robust to univariate and probabilistic sensitivity analysis.

Conclusion/Significance

Universal access to modern contraceptives in Uganda appears to be highly cost-effective. Increasing contraceptive coverage should be considered among Uganda''s public health priorities.     

The Potential Cost and Benefits of Raltegravir in Simplified Second-Line Therapy among HIV Infected Patients in Nigeria and South Africa

Background

There is an urgent need to improve the evidence base for provision of second-line antiretroviral therapy (ART) following first-line virological failure. This is particularly the case in Sub-Saharan Africa where 70% of all people living with HIV/AIDS (PHA) reside. The aim of this study was to simulate the potential risks and benefits of treatment simplification in second-line therapy compared to the current standard of care (SOC) in a lower-middle income and an upper-middle income country in Sub-Saharan Africa.

Methods

We developed a microsimulation model to compare outcomes associated with reducing treatment discontinuations between current SOC for second-line therapy in South Africa and Nigeria and an alternative regimen: ritonavir-boosted lopinavir (LPV/r) combined with raltegravir (RAL). We used published studies and collaborating sites to estimate efficacy, adverse effect and cost. Model outcomes were reported as incremental cost effectiveness ratios (ICERs) in 2011 USD per quality adjusted life year ($/QALY) gained.

Results

Reducing treatment discontinuations with LPV/r+RAL resulted in an additional 0.4 discounted QALYs and increased the undiscounted life expectancy by 0.8 years per person compared to the current SOC. The average incremental cost was $6,525 per treated patient in Nigeria and $4,409 per treated patient in South Africa. The cost-effectiveness ratios were $16,302/QALY gained and $11,085/QALY gained for Nigeria and South Africa, respectively. Our results were sensitive to the probability of ART discontinuation and the unit cost for RAL.

Conclusions

The combination of raltegravir and ritonavir-boosted lopinavir was projected to be cost-effective in South Africa. However, at its current price, it is unlikely to be cost-effective in Nigeria.     

Cost-Effectiveness of Pre-Exposure Prophylaxis (PrEP) in Preventing HIV-1 Infections in Rural Zambia: A Modeling Study

Background

Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine effectively prevents new HIV infections. The optimal scenario for implementing PrEP where most infections are averted at the lowest cost is unknown. We determined the impact of different PrEP strategies on averting new infections, prevalence, drug resistance and cost-effectiveness in Macha, a rural setting in Zambia.

Methods

A deterministic mathematical model of HIV transmission was constructed using data from the Macha epidemic (antenatal prevalence 7.7%). Antiretroviral therapy is started at CD4<350 cells/mm³. We compared the number of infections averted, cost-effectiveness, and potential emergence of drug resistance of two ends of the prioritization spectrum: prioritizing PrEP to half of the most sexually active individuals (5–15% of the total population), versus randomly putting 40–60% of the total population on PrEP.

Results

Prioritizing PrEP to individuals with the highest sexual activity resulted in more infections averted than a non-prioritized strategy over ten years (31% and 23% reduction in new infections respectively), and also a lower HIV prevalence after ten years (5.7%, 6.4% respectively). The strategy was very cost-effective at $323 per quality adjusted life year gained and appeared to be both less costly and more effective than the non-prioritized strategy. The prevalence of drug resistance due to PrEP was as high as 11.6% when all assumed breakthrough infections resulted in resistance, and as low as 1.3% when 10% of breakthrough infections resulted in resistance in both our prioritized and non-prioritized scenarios.

Conclusions

Even in settings with low test rates and treatment retention, the use of PrEP can still be a useful strategy in averting infections. Our model has shown that PrEP is a cost-effective strategy for reducing HIV incidence, even when adherence is suboptimal and prioritization is imperfect.     

Clinical Effectiveness and Cost-Effectiveness of HIV Pre-Exposure Prophylaxis in Men Who Have Sex with Men: Risk Calculators for Real-World Decision-Making

Background

Oral pre-exposure prophylaxis (PrEP) can be clinically effective and cost-effective for HIV prevention in high-risk men who have sex with men (MSM). However, individual patients have different risk profiles, real-world populations vary, and no practical tools exist to guide clinical decisions or public health strategies. We introduce a practical model of HIV acquisition, including both a personalized risk calculator for clinical management and a cost-effectiveness calculator for population-level decisions.

Methods

We developed a decision-analytic model of PrEP for MSM. The primary clinical effectiveness and cost-effectiveness outcomes were the number needed to treat (NNT) to prevent one HIV infection, and the cost per quality-adjusted life-year (QALY) gained. We characterized patients according to risk factors including PrEP adherence, condom use, sexual frequency, background HIV prevalence and antiretroviral therapy use.

Results

With standard PrEP adherence and national epidemiologic parameters, the estimated NNT was 64 (95% uncertainty range: 26, 176) at a cost of $160,000 (cost saving, $740,000) per QALY – comparable to other published models. With high (35%) HIV prevalence, the NNT was 35 (21, 57), and cost per QALY was $27,000 (cost saving, $160,000), and with high PrEP adherence, the NNT was 30 (14, 69), and cost per QALY was $3,000 (cost saving, $200,000). In contrast, for monogamous, serodiscordant relationships with partner antiretroviral therapy use, the NNT was 90 (39, 157) and cost per QALY was $280,000 ($14,000, $670,000).

Conclusions

PrEP results vary widely across individuals and populations. Risk calculators may aid in patient education, clinical decision-making, and cost-effectiveness evaluation.     

HIV Cure Strategies: How Good Must They Be to Improve on Current Antiretroviral Therapy?

Background

We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART).

Methods

We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY.

Results

For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving.

Conclusions

Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV.     

Expanding ART for treatment and prevention of HIV in South Africa: estimated cost and cost-effectiveness 2011-2050

Background

Antiretroviral Treatment (ART) significantly reduces HIV transmission. We conducted a cost-effectiveness analysis of the impact of expanded ART in South Africa.

Methods

We model a best case scenario of 90% annual HIV testing coverage in adults 15–49 years old and four ART eligibility scenarios: CD4 count <200 cells/mm³ (current practice), CD4 count <350, CD4 count <500, all CD4 levels. 2011–2050 outcomes include deaths, disability adjusted life years (DALYs), HIV infections, cost, and cost per DALY averted. Service and ART costs reflect South African data and international generic prices. ART reduces transmission by 92%. We conducted sensitivity analyses.

Results

Expanding ART to CD4 count <350 cells/mm³ prevents an estimated 265,000 (17%) and 1.3 million (15%) new HIV infections over 5 and 40 years, respectively. Cumulative deaths decline 15%, from 12.5 to 10.6 million; DALYs by 14% from 109 to 93 million over 40 years. Costs drop $504 million over 5 years and $3.9 billion over 40 years with breakeven by 2013. Compared with the current scenario, expanding to <500 prevents an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. Expanding to all CD4 levels decreases HIV infections by 3.3 million (45%) and costs by $10 billion over 40 years, with breakeven by 2023. By 2050, using higher ART and monitoring costs, all CD4 levels saves $0.6 billion versus current; other ART scenarios cost $9–194 per DALY averted. If ART reduces transmission by 99%, savings from all CD4 levels reach $17.5 billion. Sensitivity analyses suggest that poor retention and predominant acute phase transmission reduce DALYs averted by 26% and savings by 7%.

Conclusion

Increasing the provision of ART to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden. Feasibility including HIV testing and ART uptake, retention, and adherence should be evaluated.     

Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis

Background

Xpert MTB/RIF (Xpert) is a promising new rapid diagnostic technology for tuberculosis (TB) that has characteristics that suggest large-scale roll-out. However, because the test is expensive, there are concerns among TB program managers and policy makers regarding its affordability for low- and middle-income settings.

Methods and Findings

We estimate the impact of the introduction of Xpert on the costs and cost-effectiveness of TB care using decision analytic modelling, comparing the introduction of Xpert to a base case of smear microscopy and clinical diagnosis in India, South Africa, and Uganda. The introduction of Xpert increases TB case finding in all three settings; from 72%–85% to 95%–99% of the cohort of individuals with suspected TB, compared to the base case. Diagnostic costs (including the costs of testing all individuals with suspected TB) also increase: from US$28–US$49 to US$133–US$146 and US$137–US$151 per TB case detected when Xpert is used “in addition to” and “as a replacement of” smear microscopy, respectively. The incremental cost effectiveness ratios (ICERs) for using Xpert “in addition to” smear microscopy, compared to the base case, range from US$41–$110 per disability adjusted life year (DALY) averted. Likewise the ICERS for using Xpert “as a replacement of” smear microscopy range from US$52–$138 per DALY averted. These ICERs are below the World Health Organization (WHO) willingness to pay threshold.

Conclusions

Our results suggest that Xpert is a cost-effective method of TB diagnosis, compared to a base case of smear microscopy and clinical diagnosis of smear-negative TB in low- and middle-income settings where, with its ability to substantially increase case finding, it has important potential for improving TB diagnosis and control. The extent of cost-effectiveness gain to TB programmes from deploying Xpert is primarily dependent on current TB diagnostic practices. Further work is required during scale-up to validate these findings. Please see later in the article for the Editors'' Summary     

Cost-Effectiveness of Quantiferon?-TB Gold-In-Tube Versus Tuberculin Skin Testing for Contact Screening and Treatment of Latent Tuberculosis Infection in Brazil

Background

Latent tuberculosis infection (LTBI) is a reservoir for new TB cases. Isoniazid preventive therapy (IPT) reduces the risk of active TB by as much as 90%, but LTBI screening has limitations. Unlike tuberculin skin testing (TST), interferon-gamma release assays are not affected by BCG vaccination, and have been reported to be cost-effective in low-burden countries. The goal of this study was to perform a cost-effectiveness analysis from the health system perspective, comparing three strategies for LTBI diagnosis in TB contacts: tuberculin skin testing (TST), QuantiFERON®-TB Gold-in-Tube (QFT-GIT) and TST confirmed by QFT-GIT if positive (TST/QFT-GIT) in Brazil, a middle-income, high-burden country with universal BCG coverage.

Methodology/Principal Findings

Costs for LTBI diagnosis and treatment of a hypothetical cohort of 1,000 adult immunocompetent close contacts were considered. The effectiveness measure employed was the number of averted TB cases in two years. Health system costs were US$ 105,096 for TST, US$ 121,054 for QFT-GIT and US$ 101,948 for TST/QFT-GIT; these strategies averted 6.56, 6.63 and 4.59 TB cases, respectively. The most cost-effective strategy was TST (US$ 16,021/averted case). The incremental cost-effectiveness ratio was US$ 227,977/averted TB case for QFT-GIT. TST/QFT-GIT was dominated.

Conclusions

Unlike previous studies, TST was the most cost-effective strategy for averting new TB cases in the short term. QFT-GIT would be more cost-effective if its costs could be reduced to US$ 26.95, considering a TST specificity of 59% and US$ 18 considering a more realistic TST specificity of 80%. Nevertheless, with TST, 207.4 additional people per 1,000 will be prescribed IPT compared with QFT.     

Cost-effectiveness of pre-referral antimalarial, antibacterial, and combined rectal formulations for severe febrile illness

Background

Malaria and bacterial infections account for most infectious disease deaths in developing countries. Prompt treatment saves lives, but rapid deterioration often prevents the use of oral therapies; delays in reaching health facilities providing parenteral interventions are common. Rapidly and reliably absorbed antimalarial/antibacterial rectal formulations used in the community could prevent deaths and disabilities. Rectal antimalarial treatments are currently available; rectal antibacterial treatments are yet to be developed. Assessment of the likely cost-effectiveness of these interventions will inform research priorities and implementation.

Methods and Findings

The burden of malaria and bacterial infections worldwide and in Sub-Saharan and Southern Africa (SSA) and South and South-East Asia (SEA) was summarised using published data. The additional healthcare costs (US$) per death and per Disability Adjusted Life Year (DALY) avoided following pre-referral treatment of severe febrile illness with rectal antimalarials, antibacterials or combined antimalarial/antibacterials in populations at malaria risk in SSA/SEA were assessed. 46 million severe malaria and bacterial infections and 5 million deaths occur worldwide each year, mostly in SSA/SEA. At annual delivery costs of $0.02/capita and 100% coverage, rectal antimalarials ($2 per dose) would avert 240,000 deaths in SSA and 7,000 deaths in SEA at $5 and $177 per DALY avoided, respectively; rectal antibacterials ($2 per dose) would avert 130,000 deaths in SSA and 27,000 deaths in SEA at $19 and $97 per DALY avoided, respectively. Combined rectal formulations ($2.50 per dose) would avert 370,000 deaths in SSA and 33,000 deaths in SEA at $8 and $79 per DALY avoided, respectively, and are a cost-effective alternative to rectal antimalarials or antibacterials alone.

Conclusions

Antimalarial, antibacterial and combined rectal formulations are likely to be cost-effective interventions for severe febrile illness in the community. Attention should focus on developing effective rectal antibacterials and ensuring that these lifesaving treatments are used in a cost-effective manner.     

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.     

Cost-Effectiveness of HIV Drug Resistance Testing to Inform Switching to Second Line Antiretroviral Therapy in Low Income Settings

Background

To guide future need for cheap resistance tests for use in low income settings, we assessed cost-effectiveness of drug resistance testing as part of monitoring of people on first line ART - with switching from first to second line ART being conditional on NNRTI drug resistance mutations being identified.

Methods

An individual level simulation model of HIV transmission, progression and the effect of ART which accounts for adherence and resistance development was used to compare outcomes of various potential monitoring strategies in a typical low income setting in sub-Saharan Africa. Underlying monitoring strategies considered were based on clinical disease, CD4 count or viral load. Within each we considered a strategy in which no further measures are performed, one with a viral load measure to confirm failure, and one with both a viral load measure and a resistance test. Predicted outcomes were assessed over 2015–2025 in terms of viral suppression, first line failure, switching to second line regimen, death, HIV incidence, disability-adjusted-life-years averted and costs. Potential future low costs of resistance tests ($30) were used.

Results

The most effective strategy, in terms of DALYs averted, was one using viral load monitoring without confirmation. The incremental cost-effectiveness ratio for this strategy was $2113 (the same as that for viral load monitoring with confirmation). ART monitoring strategies which involved resistance testing did not emerge as being more effective or cost effective than strategies not using it. The slightly reduced ART costs resulting from use of resistance testing, due to less use of second line regimens, was of similar magnitude to the costs of resistance tests.

Conclusion

Use of resistance testing at the time of first line failure as part of the decision whether to switch to second line therapy was not cost-effective, even though the test was assumed to be very inexpensive.     

Obstructed labor and caesarean delivery: the cost and benefit of surgical intervention

Background

Although advances in the reduction of maternal mortality have been made, up to 273,000 women will die this year from obstetric etiologies. Obstructed labor (OL), most commonly treated with Caesarean delivery, has been identified as a major contributor to global maternal morbidity and mortality. We used economic and epidemiological modeling to estimate the cost per disability-adjusted life-year (DALY) averted and benefit-cost ratio of treating OL with Caesarean delivery for 49 countries identified as providing an insufficient number of Caesarean deliveries to meet demand.

Methods and Findings

Using publicly available data and explicit economic assumptions, we estimated that the cost per DALY (3,0,0) averted for providing Caesarean delivery for OL ranged widely, from $251 per DALY averted in Madagascar to $3,462 in Oman. The median cost per DALY averted was $304. Benefit-cost ratios also varied, from 0.6 in Zimbabwe to 69.9 in Gabon. The median benefit-cost ratio calculated was 6.0. The main limitation of this study is an assumption that lack of surgical capacity is the main factor responsible for DALYs from OL.

Conclusions

Using the World Health Organization''s cost-effectiveness standards, investing in Caesarean delivery can be considered “highly cost-effective” for 48 of the 49 countries included in this study. Furthermore, in 46 of the 49 included countries, the benefit-cost ratio was greater than 1.0, implying that investment in Caesarean delivery is a viable economic proposition. While Caesarean delivery alone is not sufficient for combating OL, it is necessary, cost-effective by WHO standards, and ultimately economically favorable in the vast majority of countries included in this study.     

Cost-Effectiveness of Peer Counselling for the Promotion of Exclusive Breastfeeding in Uganda

Background

Community based breastfeeding promotion programmes have been shown to be effective in increasing breastfeeding prevalence. However, there is limited data on the cost-effectiveness of these programmes in sub-Saharan Africa. This paper evaluates the cost-effectiveness of a breastfeeding promotion intervention targeting mothers and their 0 to 6 month old children.

Methods

Data were obtained from a community randomized trial conducted in Uganda between 2006–2008, and supplemented with evidence from several studies in sub-Saharan Africa. In the trial, peer counselling was offered to women in intervention clusters. In the control and intervention clusters, women could access standard health facility breastfeeding promotion services (HFP). Thus, two methods of breastfeeding promotion were compared: community based peer counselling (in addition to HFP) and standard HFP alone. A Markov model was used to calculate incremental cost-effectiveness ratios between the two strategies. The model estimated changes in breastfeeding prevalence and disability adjusted life years. Costs were estimated from a provider perspective. Uncertainty around the results was characterized using one-way sensitivity analyses and a probabilistic sensitivity analysis.

Findings

Peer counselling more than doubled the breastfeeding prevalence as reported by mothers, but there was no observable impact on diarrhoea prevalence. Estimated incremental cost-effectiveness ratios were US$68 per month of exclusive or predominant breastfeeding and U$11,353 per disability adjusted life year (DALY) averted. The findings were robust to parameter variations in the sensitivity analyses

Conclusions

Our strategy to promote community based peer counselling is unlikely to be cost-effective in reducing diarrhoea prevalence and mortality in Uganda, because its cost per DALY averted far exceeds the commonly assumed willingness-to-pay threshold of three times Uganda’s GDP per capita (US$1653). However, since the intervention significantly increases prevalence of exclusive or predominant breastfeeding, it could be adopted in Uganda if benefits other than reducing the occurrence of diarrhoea are believed to be important.     

Male Circumcision at Different Ages in Rwanda: A Cost-Effectiveness Study

Background

There is strong evidence showing that male circumcision (MC) reduces HIV infection and other sexually transmitted infections (STIs). In Rwanda, where adult HIV prevalence is 3%, MC is not a traditional practice. The Rwanda National AIDS Commission modelled cost and effects of MC at different ages to inform policy and programmatic decisions in relation to introducing MC. This study was necessary because the MC debate in Southern Africa has focused primarily on MC for adults. Further, this is the first time, to our knowledge, that a cost-effectiveness study on MC has been carried out in a country where HIV prevalence is below 5%.

Methods and Findings

A cost-effectiveness model was developed and applied to three hypothetical cohorts in Rwanda: newborns, adolescents, and adult men. Effectiveness was defined as the number of HIV infections averted, and was calculated as the product of the number of people susceptible to HIV infection in the cohort, the HIV incidence rate at different ages, and the protective effect of MC; discounted back to the year of circumcision and summed over the life expectancy of the circumcised person. Direct costs were based on interviews with experienced health care providers to determine inputs involved in the procedure (from consumables to staff time) and related prices. Other costs included training, patient counselling, treatment of adverse events, and promotion campaigns, and they were adjusted for the averted lifetime cost of health care (antiretroviral therapy [ART], opportunistic infection [OI], laboratory tests). One-way sensitivity analysis was performed by varying the main inputs of the model, and thresholds were calculated at which each intervention is no longer cost-saving and at which an intervention costs more than one gross domestic product (GDP) per capita per life-year gained. Results: Neonatal MC is less expensive than adolescent and adult MC (US$15 instead of US$59 per procedure) and is cost-saving (the cost-effectiveness ratio is negative), even though savings from infant circumcision will be realized later in time. The cost per infection averted is US$3,932 for adolescent MC and US$4,949 for adult MC. Results for infant MC appear robust. Infant MC remains highly cost-effective across a reasonable range of variation in the base case scenario. Adolescent MC is highly cost-effective for the base case scenario but this high cost-effectiveness is not robust to small changes in the input variables. Adult MC is neither cost-saving nor highly cost-effective when considering only the direct benefit for the circumcised man.

Conclusions

The study suggests that Rwanda should be simultaneously scaling up circumcision across a broad range of age groups, with high priority to the very young. Infant MC can be integrated into existing health services (i.e., neonatal visits and vaccination sessions) and over time has better potential than adolescent and adult circumcision to achieve the very high coverage of the population required for maximal reduction of HIV incidence. In the presence of infant MC, adolescent and adult MC would evolve into a “catch-up” campaign that would be needed at the start of the program but would eventually become superfluous. Please see later in the article for the Editors'' Summary     

HIV screening via fourth-generation immunoassay or nucleic acid amplification test in the United States: a cost-effectiveness analysis

Background

At least 10% of the 56,000 annual new HIV infections in the United States are caused by individuals with acute HIV infection (AHI). It unknown whether the health benefits and costs of routine nucleic acid amplification testing (NAAT) are justified, given the availability of newer fourth-generation immunoassay tests.

Methods

Using a dynamic HIV transmission model instantiated with U.S. epidemiologic, demographic, and behavioral data, I estimated the number of acute infections identified, HIV infections prevented, quality-adjusted life years (QALYs) gained, and the cost-effectiveness of alternative screening strategies. I varied the target population (everyone aged 15-64, injection drug users [IDUs] and men who have sex with men [MSM], or MSM only), screening frequency (annually, or every six months), and test(s) utilized (fourth-generation immunoassay only, or immunoassay followed by pooled NAAT).

Results

Annual immunoassay testing of MSM reduces incidence by 9.5% and costs <$10,000 per QALY gained. Adding pooled NAAT identifies 410 AHI per year, prevents 9.6% of new cases, costs $92,000 per QALY gained, and remains <$100,000 per QALY gained in settings where undiagnosed HIV prevalence exceeds 4%. Screening IDUs and MSM annually with fourth-generation immunoassay reduces incidence by 13% with cost-effectiveness <$10,000 per QALY gained. Increasing the screening frequency to every six months reduces incidence by 11% (MSM only) or 16% (MSM and IDUs) and costs <$20,000 per QALY gained.

Conclusions

Pooled NAAT testing every 12 months of MSM and IDUs in the United States prevents a modest number of infections, but may be cost-effective given sufficiently high HIV prevalence levels. However, testing via fourth-generation immunoassay every six months prevents a greater number of infections, is more economically efficient, and may obviate the benefits of acute HIV screening via NAAT.     

The Cost and Cost-Effectiveness of Scaling up Screening and Treatment of Syphilis in Pregnancy: A Model

Background

Syphilis in pregnancy imposes a significant global health and economic burden. More than half of cases result in serious adverse events, including infant mortality and infection. The annual global burden from mother-to-child transmission (MTCT) of syphilis is estimated at 3.6 million disability-adjusted life years (DALYs) and $309 million in medical costs. Syphilis screening and treatment is simple, effective, and affordable, yet, worldwide, most pregnant women do not receive these services. We assessed cost-effectiveness of scaling-up syphilis screening and treatment in existing antenatal care (ANC) programs in various programmatic, epidemiologic, and economic contexts.

Methods and Findings

We modeled the cost, health impact, and cost-effectiveness of expanded syphilis screening and treatment in ANC, compared to current services, for 1,000,000 pregnancies per year over four years. We defined eight generic country scenarios by systematically varying three factors: current maternal syphilis testing and treatment coverage, syphilis prevalence in pregnant women, and the cost of healthcare. We calculated program and net costs, DALYs averted, and net costs per DALY averted over four years in each scenario. Program costs are estimated at $4,142,287 – $8,235,796 per million pregnant women (2010 USD). Net costs, adjusted for averted medical care and current services, range from net savings of $12,261,250 to net costs of $1,736,807. The program averts an estimated 5,754 – 93,484 DALYs, yielding net savings in four scenarios, and a cost per DALY averted of $24 – $111 in the four scenarios with net costs. Results were robust in sensitivity analyses.

Conclusions

Eliminating MTCT of syphilis through expanded screening and treatment in ANC is likely to be highly cost-effective by WHO-defined thresholds in a wide range of settings. Countries with high prevalence, low current service coverage, and high healthcare cost would benefit most. Future analyses can be tailored to countries using local epidemiologic and programmatic data.