Efficiency of health system, not just better regimens, critical to reducing mother-to-child HIV cases

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Reducing the number of children infected with HIV and ensuring that mothers have access to life-saving treatment will only happen when systems perform with greater than 90% efficiency at each step of the prevention of mother-to-child transmission (PMTCT) process, from counselling and testing to delivery of antiretrovirals, according to Pierre M Barker and colleagues in a modelling study published in the advance online edition of the Journal of Acquired Immune Deficiency Syndromes.

More effective antiretroviral combinations or starting antiretrovirals at higher CD4 cell counts will have a very limited effect on the rates of mother-to-child transmission and gains in maternal survival unless the performance of the health system is addressed, the authors add.

 The elimination of mother-to-child transmission and gains in maternal survival from HIV infection are possible with effective antiretroviral treatment.

Glossary

antenatal

The period of time from conception up to birth.

mother-to-child transmission (MTCT)

Transmission of HIV from a mother to her unborn child in the womb or during birth, or to infants via breast milk. Also known as vertical transmission.

middle income countries

The World Bank classifies countries according to their income: low, lower-middle, upper-middle and high. There are around 50 lower-middle income countries (mostly in Africa and Asia) and around 60 upper-middle income countries (in Africa, Eastern Europe, Asia, Latin America and the Caribbean).

mathematical models

A range of complex mathematical techniques which aim to simulate a sequence of likely future events, in order to estimate the impact of a health intervention or the spread of an infection.

protocol

A detailed research plan that describes the aims and objectives of a clinical trial and how it will be conducted.

 However, PMTCT involves a number of sequential steps. Failure at any step in the process will result in considerable cumulative loss of pregnant women (to follow-up) resulting in increased risk of transmission, note the authors.

These steps include: counselling, HIV testing, CD4 testing, antiretroviral distribution at antenatal care clinics and labour wards, and testing of infants at six weeks.

 The authors cite the example of infants attending immunisation clinics in South Africa where in spite of single-dose nevirapine (sdNVP) offered at antenatal clinics, 21% of HIV-exposed infants were HIV-infected when tested six weeks after birth.

 The authors explain if PMTCT is limited to three core steps even minimal losses at each step will have a significant effect on outcomes.

The three core steps include: 1) attending an antenatal care clinic 2) counselled and tested for HIV and 3) getting antiretrovirals before and during birth.

If each step happens with 95% reliability, a 5% loss compounded at each following step will result in 86% of women receiving antiretrovirals; 80% reliability (20% loss at each step) results in 51% of women getting antiretrovirals and at 60% reliability this translates into only 22% of women getting treatment.

The authors note this helps explain why in 2009 in low- and middle-income countries approximately 53% of HIV-infected women received antiretrovirals to prevent the transmission of the virus to their infants. 

The authors developed a model that estimated the effect of antiretroviral interventions for PMTCT on transmission rates in infants. The model compared the differences in performance of the many steps of different PMTCT protocols using hypothetical and reported data from a PMTCT programme in a large province in South Africa.

The model was limited to antenatal and peripartum interventions, with the primary outcome defined as the HIV status of infants born to HIV-infected mothers at six weeks of age. Transmission after birth, because of breastfeeding, primary infection of a pregnant women or when a pregnant women might not test positive, for example with a newly-acquired HIV-infection was not included.

The authors looked at six scenarios reflecting actual PMTCT practices in different settings. These scenarios were then tested in a model (from South Africa) that used reported performance data for each of the three core steps described above.

  1. No intervention to HIV-infected women or HIV-exposed infants.

  2. HIV-infected women receive single-dose nevirapine (sdNVP)in labour. HIV-exposed infants receive sdNVP after delivery.

  3. HIV-infected women receive zidovudine (AZT) any time from 28 weeks of gestation and sdNVP in labour. HIV-exposed infants receive sdNVP and AZT one week after delivery.

  4. A 2-tier system in which HIV-infected women who do not fulfil criteria for lifelong ART and their infants receive sdNVP as in setting number 2, whereas HIV-infected women who do fulfil criteria are initiated on ART by 34 weeks of gestation. Eligibility for ART was set at CD4 counts <200 cells/mm³.

  5. A 2-tier system in which HIV-infected women who do not fulfil criteria for lifelong ART and their infants receive AZT and sdNVP as in setting number 3, whereas HIV-infected women who do fulfil criteria (CD4 count <200 cells/mm³. are initiated on lifelong ART by 34 weeks of gestation.

  6. A 2-tier system in which HIV-infected women who do not fulfil criteria for lifelong ART received triple antiretroviral prophylaxis (for example, AZT/3TC/Kaletra) for the duration of pregnancy, whereas HIV-infected women who do not fulfil criteria (CD4 count <200 cells/mm³.) are initiated on lifelong ART by 34 weeks of gestation.

The authors found that in scenario 4 in a health system functioning at the reported South Africa performance levels for each of the three steps, only one third of the mothers and their infants would get sdNVP or ART, with the expected reduction of vertical transmission rate to be approximately 8%. The remaining two-thirds of women would be lost during the process and have an anticipated 25% transmission rate. So the overall transmission rate would be 19.5%.

Introducing AZT as part of the protocol as in scenario 5 would make a minimal difference in the overall transmission rate bringing it down to 17%.

However, improved reliability to 95% efficiency in both scenarios 4 and 5 would have a significant impact on transmission rates reducing them to 9.4% and 4.1%, respectively.

The authors also found with at current South African performance levels raising the eligibility criteria in two-tier models from CD4 <200 cells/mm³ to CD4 <350 cells/mm³, while certainly improving the mother’s health, had little effect on the transmission rate (18.2% compared to 15.3%).

The authors underscore that without being able to deliver each step in the PMTCT process at greater than 90% efficiency and address health system performance, effective antiretroviral treatments and other interventions will not make any real difference in transmission rates.

The authors, while recognising human and financial constraints, suggest that initiatives to improve both the quality and reliability of services within the health system be matched with initiatives to increase the demand for services. Adding that “the simplification of protocols and methods to monitor and improve local performance will help.” 

The authors suggest that quality improvement methods and other strategies including task-shifting can provide benefits in a relatively short time.

They add, “However, unless strategies to improve PMTCT delivery are energetically and resolutely pursued, then ARVs will remain in cupboards. Such interventions would not just improve PMTCT services but could strengthen essential maternal and child health services and related health information services.”

The authors conclude “Investments in and support for the mechanisms of delivering and sustaining PMTCT interventions at scale are required if gains in maternal and child survival are to be realised in countries highly affected by HIV.”

References

Barker PM et al. Antiretroviral drugs in the cupboard are not enough: the impact of health systems’ performance on mother-to-child transmission. Advance on line edition J Acquir immune Defic Syndr, November 16, 2010. Link to abstract.