ART for life cost effective for prevention of mother-to-child transmission in Uganda

Combination antiretroviral therapy (ART) provided to all pregnant women with HIV who have CD4 cell counts under 350 cells/mm³ (World Health Organization Option B) in Uganda appears to be highly cost effective for the prevention of mother-to-child transmission (PMTCT), even if continued over the mother’s lifetime, when compared to single-dose nevirapine, two-drug therapy or no treatment, Andreas Kuznik and colleagues report in a mathematical modelling study published in the August edition of the Bulletin of the World Health Organization.

Eighteen months of ART compared to single-dose nevirapine, dual therapy or no therapy prevented 5.21, 3.22 and 8.58 disability-adjusted life years (DALYs), respectively, with a corresponding incremental cost for each DALY averted of US$46, US$99 and US$34.

DALYs refer to the number of years of life saved in the Ugandan context assuming HIV infection is prevented.

Uganda’s gross domestic product (GDP) in 2009 was US$490 per person. The World Health Organization (WHO) considers a health intervention cost effective and highly cost effective if the cost for each DALY averted is less than three times the GDP and less than the GDP, respectively.

Sensitivity analyses showed expanding treatment to include all eligible women currently untreated appeared to be cost effective, assuming adherence does not fall below 40%.

The only clinical outcome included in the analysis was mother-to-child transmission of HIV. The authors did not look at how ART benefited maternal life expectancy or take into account its mitigating effect on transmission to any uninfected sexual partners of the mother. Consequently they believe their findings to be conservative.

There are approximately 12 million women with HIV in sub-Saharan Africa who are of childbearing age and, each year, they account for an estimated 1.4 million pregnancies at risk for mother-to-child transmission.

Uganda has the second highest fertility rate in the world, of 6.7 children for each woman. Approximately 91,000 infants are born each year to women with HIV. Barely half of these women get any kind of PMTCT intervention. In 2009, mother-to-child transmission accounted for approximately one in four of the 110,000 new HIV infections in Uganda.

Of those women who did get any antiretroviral drugs for PMTCT, close to 60% received single-dose nevirapine while a quarter got dual therapy comprising zidovudine and lamivudine for seven weeks and 17% got ART.

Following the WHO 2010 PMTCT guidelines proposing programme options A and B, Uganda adopted Option B in 2011. Once adequate resources are available all Ugandan health facilities are expected to follow Option B.

The authors believe this to be the first published study to look at the cost-effectiveness of lifelong ART for PMTCT.

Having developed a decision-based analytical model from the perspective of the Uganda national health system, they looked at the cost-effectiveness of 18 months of ART for PMTCT relative to other antiretroviral strategies for PMTCT (single-dose nevirapine, dual therapy or no treatment); the cost-effectiveness of lifelong ART and of expanding ART access to eligible untreated women. 

Evaluation of the cost-effectiveness of ART was based on the assumption ART reduces the risk of transmission to the baby from 40% when the woman is not taking any treatment; to 25.8% with single-dose nevirapine (total drug cost US$0.06); to 17.4% with dual therapy (US$15.63) and to 3.8% with ART for 18 months (total annual cost US$469.77). 

Lifelong ART at a cost of US$6883 was anticipated to provide the same risk reduction in each subsequent pregnancy. 

Eighteen months of ART was calculated as highly cost effective, relative to other therapies or no treatment, as follows: based on discounted differences in life expectancy between HIV-negative (53.25 years) and HIV-positive children (less than two years without treatment; 14.23 years with ART) the authors estimated each child infection is associated with 23.70 DALYs.

The cost of ART for 18 months is US$482 for each person. The effect of ART in reducing mother-to-child transmission is associated with cost offsets of US$240 and US$148 for each person relative to single-dose nevirapine and dual therapy, respectively.

So the total net incremental cost of ART for each pregnancy was estimated to be US$242 (482-240) and US$318 (482-148) relative to single-dose nevirapine and dual therapy, respectively. However, ART averts a mean of 5.21 DALYs and 3.22 DALYs relative to single-dose nevirapine and dual therapy, respectively.

So the cost of ART for each DALY averted was approximately US$46 (US$242 divided by 5.21) and US$99 (US$318 divided by 3.22) relative to single-dose nevirapine and dual therapy, respectively.

Similarly the incremental costs for each DALY averted because of lifelong ART are US$205, US$354 and US$172 relative to single-dose nevirapine, dual therapy and no treatment, respectively. The corresponding DALYs averted are 19.20, 11.87 and 31.60. However, lifetime ART being highly cost-effective is dependent upon the assumed effectiveness of dual therapy, note the authors.

High fertility rates are common in sub-Saharan Africa yet only four countries have reached a target of 80% PMTCT coverage, so the cost-effectiveness of lifelong ART will also depend on the number of future childbirths for each woman.

The authors believe their findings can be generalised to most countries in sub-Saharan Africa.

Limitations of the study include multiple trials rather than one randomised controlled trial used for estimates of mother to child transmission rates. So differences in demographics and study design may have influenced the results.

The risk of transmission may vary according to the clinical stage of the maternal HIV infection, whereas the authors used a constant transmission probability.

Pregnant women in Uganda usually present for antenatal care late in their pregnancy, after the fifth month. ART may be less effective when started in the late stages of pregnancy. ART is available in 109 out of 122 district hospitals. The authors suggest midwives and other healthcare workers currently giving single-dose nevirapine or dual therapy in these facilities could be trained to start ART, follow up patients and link them to local and national programmes for HIV treatment and care.

Lack of data meant the authors were unable to incorporate adherence into their lifetime model. Given that their findings with 18 months of ART were sensitive to adherence it would be more so for lifelong ART.

The authors conclude “In Uganda ART appears highly cost-effective for PMTCT, even if continued over the patients’ lifetimes. Given the additional public health benefits of ART, efforts to ensure all HIV-positive women have access to lifelong ART should be intensified.”