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Prevention of vertical transmission of HIV: analysis of cost effectiveness of options available in South Africa |
Soderlund N, Zwi K, Kinghorn A, Gray G |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The use of formula feeding and antiretroviral interventions to prevent vertical transmission of human immunodeficiency virus (HIV).
Economic study type Cost-effectiveness analysis.
Study population The study population consisted of working class, pregnant women and children born to HIV-positive mothers from urban South Africa.
Setting The setting was the community and primary care. The analysis was carried out in Johannesburg, South Africa.
Dates to which data relate The effectiveness data were taken from sources published between 1983 and 1999. The health care costs of HIV-infected children were estimated from data recorded on all paediatric admissions to the hospital of a Soweto community in south west Johannesburg between 1992 and 1997. The price year was 1998.
Source of effectiveness data The effectiveness data were derived from a review of the literature.
Modelling A Markov chain simulation model was used to replicate the natural course of transmission and disease, and to simulate the cost and effectiveness of the interventions compared. Model transitions occurred on a monthly basis for the first 9 years of life and then on an annual basis until death. A cohort of 20,000 pregnant women was analysed.
Outcomes assessed in the review The effectiveness model parameters assessed were:
the HIV infection rates,
infant mortality,
the natural rates of breast-feeding,
the proportion of infants born to HIV-infected mothers,
the efficacy of antiretroviral interventions,
the risk of transmitting the virus by breast feeding, and
the relative risk of mortality due to not breast-feeding HIV-negative children.
The online version of this paper (BMJ website) provides full details of the model inputs.
Study designs and other criteria for inclusion in the review This was a non-systematic review of the literature. The inclusion and exclusion criteria were not given.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included Approximately 16 studies were included in the review.
Methods of combining primary studies Investigation of differences between primary studies Results of the review The HIV infection rate was 15%.
The infant mortality was 35 per 1,000 live births.
The natural rate of breast-feeding was 95% (the likelihood of stopping breast-feeding/month was 14%).
The proportion of infants born to HIV-positive mothers infected at birth was 26%.
This proportion was 13% (50% reduction) with the CDC regimen, 8% (70% reduction) with the ACTG076 regimen, and 16% (37% reduction) with the PETRA regimen.
The cumulative infection risk by breast-feeding was 10% at 3 months, 13% at 6 months, 16% at 12 months, and 17% at 18 months.
The relative risk of mortality due to not breast-feeding HIV-negative children was 2.5 for 0 to 3 months, 2.0 for 3 to 6 months, and 1.5 for 6 to 12 months.
Measure of benefits used in the economic analysis The measures of benefit were the life-years gained (LYG) and the deaths averted. Survival in HIV-infected children was measured using a Weibull survival curve. The survival in HIV-infected children was 66% at one year, 46% at 2 years, 33% at 3 years, 24% at 4 years, and 9% at 8 years. The life expectancy in HIV-negative children was 66 years. The benefits were discounted at a rate of 5% per annum.
Direct costs The direct costs to the health service were included in the analysis. These were for the intervention, the health care of HIV-negative children, and the health care of HIV-positive children. The intervention costs were for counselling, screening, additional monitoring tests required, antiretroviral drugs, formula feeding, bottles, and staff time required for administering the intervention. The health care costs of HIV-positive children were for hospitalisation and outpatient attendance. More details on the derivation of the cost data were given elsewhere (Kinghorn, see Other Publications of Related Interest). The rates of use and associated costs of health care for HIV-infected children were estimated from data recorded on all paediatric admissions to the hospital between 1992 and 1997. The costs were discounted at a rate of 5% per annum. The unit costs were reported, whereas the quantities were not. The price year was 1998.
Statistical analysis of costs No statistical analysis of the costs was carried out.
Indirect Costs The indirect costs were not included in the analysis.
Currency US dollars ($). These were converted from the South African rand at the 1998 rate of R6=$1. The exchange rate for US$ to UK pounds sterling was $1.5=1.
Sensitivity analysis One-way sensitivity analyses were carried out on six model inputs. These were the rates of antenatal seroprevalence, infant mortality, the relative risk of death due to not breast-feeding, the cost of antiretroviral drugs, the levels of expenditure on child health services, and the uptake of antenatal HIV screening.
Estimated benefits used in the economic analysis The following are based on an initial cohort of 20,000 pregnant women.
The ACTG076 regime was the most effective antiretroviral intervention with 200 deaths averted and 3,655 LYG in comparison with no intervention. However, it was only marginally more effective than the combination of CDC-Thai regimen plus formula supplied (200 deaths averted and 3,654 LYG).
Options that recommended breast-feeding early on, with a change to formula feeding after 3 or 6 months, saved the least number of lives. Breast-feeding recommended from birth saved 461 life-years, while breast-feeding at 6 months saved 98 life-years.
Cost results The following are based on an initial cohort of 20,000 pregnant women.
The ACTG076 regimen was the most costly intervention by a considerable margin, with a total cost of $488,000.
More than 80% of the costs were due to expenditure on antiretroviral drugs and their administration.
All of the strategies involving formula feeding from birth resulted in considerable costs because of disease other than HIV. The total costs were $92,000 with breast-feeding recommended, $116,000 with breast-feeding to 3 months, $108,000 with breast-feeding to 6 months, and $218,000 with formula supplied.
Synthesis of costs and benefits The costs per death averted and per life-years saved were calculated for each strategy in comparison with the control (no intervention).
The authors noted that the World Development Report suggested that interventions costing less than $100 per life-year saved are cost-effective for middle income countries.
The PETRA strategy had an average cost-effective ratio of $14 per life-year saved. CDC plus formula supplied had an average cost-effectiveness ratio of $37 per life-year saved. The strategies of CDC and CDC plus formula recommended were both cost-saving as well as effective.
The most relevant analysis was an incremental cost-effectiveness analysis, which was not well presented in the article. However, it was clear that the strategy of CDC plus feeding recommended dominated (more effective and less costly) the PETRA and CDC strategies. The incremental cost-effectiveness of CDC plus free formula, compared to CDC with only a feeding recommendation, was $910 per life-year saved.
The cost-effectiveness of the interventions was most sensitive to differences in the rates of antenatal seroprevalence.
The strategy of breast-feeding formula recommended became cost-saving at a rate of antenatal seroprevalence of 30%.
When breast-feeding was associated with a strong protective effect, or when infant mortality exceeded around 70 to 140 per 1,000, formula feeding interventions were contraindicated. The results of the model were moderately sensitive to changes in expenditure on child health services.
Authors' conclusions The administration of a low-cost antiretroviral regimen and/or advocating formula feeding for infants of human immunodeficiency virus (HIV)-infected women would save lives and, in many cases, would also save money. The appropriateness of formula feeding was highly cost-effective only in settings with high seroprevalence and reasonable levels of child survival, and was dangerous where infant mortality was high or the protective effect of breast-feeding was substantial.
CRD COMMENTARY - Selection of comparators The authors justified the comparators used. These technologies represented potential alternatives to prevent vertical transmission of HIV and no intervention was the natural alternative. You should consider whether these technologies are widely used technologies in your own setting.
Validity of estimate of measure of effectiveness The internal validity of the estimates of benefit could not be objectively assessed due to the lack of a comprehensive review of the literature. Also, because there was no quality assessment of the primary studies included in the review. However, uncertainties in the main parameters were comprehensively explored in the sensitivity analyses.
Validity of estimate of measure of benefit The estimation of the benefits was modelled. The decision-analysis model used to derive the deaths averted and LYG was appropriate.
Validity of estimate of costs Further details on the derivation of the cost data were provided elsewhere. Thus, it is not certain whether all of the relevant costs have been included in the analysis. However, it is worth noting that if a broader perspective had been used, the cost results for the optimal strategy (CDC plus formula feeding recommendation) would have been higher since the patients would have to buy the formula. The costs and the quantities were not reported separately. The price year was reported and the direct costs were discounted.
Other issues As mentioned in the 'Validity of Estimate of Costs' section, if a broader perspective had been used, the cost results for the optimal strategy would have been higher since the patients would have to buy the formula. The authors made appropriate comparisons of their findings with those from other studies. The issue of generalisability to other countries was illustrated in the sensitivity analyses. The authors acknowledged that their study did not allow a description of all possible combinations of alternatives. The authors did not report any other further limitation to their study. The incremental cost-effectiveness analysis was not well presented. The topic studied and the findings reported are of high interest.
Implications of the study The findings of the study suggested that the recommendation of formula feeding for babies of HIV-positive mothers is contraindicated in areas of high infant mortality. Pilot projects are required to test the feasibility and acceptability of such strategies.
Bibliographic details Soderlund N, Zwi K, Kinghorn A, Gray G. Prevention of vertical transmission of HIV: analysis of cost effectiveness of options available in South Africa. BMJ 1999; 318: 1650-1656 Other publications of related interest Dabis F, Msellati P, Meda N, et al. 6-month efficacy, tolerance, and acceptability of a short regimen of oral zidovudine to reduce vertical transmission of HIV in breastfed children in Cote d'Ivoire and Burkina Faso: a double-blind placebo-controlled multicentre trail. Lancet 1999;353:786-92.
Marseilles E, Kahn JG, Saba J. Cost-effectiveness of anti-retroviral drug therapy to reduce mother-to-child HIV transmission in Sub-Saharan Africa. AIDS 1998;12:939-48.
Kinghorn AW. Projections of the costs of anti-retroviral interventions to reduce mother-to-child transmission of HIV in the South African public sector. Johannesburg: HIV Management Services Technical Report; 1998.
Indexing Status Subject indexing assigned by NLM MeSH Acquired Immunodeficiency Syndrome /economics /prevention & Breast Feeding; Cohort Studies; Cost-Benefit Analysis; Female; Food, Formulated; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infectious Disease Transmission, Vertical /economics /prevention & Life Expectancy; Markov Chains; Pregnancy; Pregnancy Complications, Infectious /economics; South Africa; control; control /transmission AccessionNumber 21999008177 Date bibliographic record published 31/01/2004 Date abstract record published 31/01/2004 |
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