Malawi plans 'test and treat' approach for pregnant women to cut mother-to-child HIV transmission

Malawi’s Ministry of Health is planning to provide triple-drug antiretroviral therapy (ART) to all pregnant women with HIV as the most practical way for the country’s impoverished health system to quickly reduce transmission of HIV from mother to child – and protect mother’s lives at the same time – the Eighteenth International AIDS Conference heard yesterday.

New guidance from the World Health Organization (WHO) recommends that women diagnosed with HIV during pregnancy and with CD4 counts below 350 cells/mm³ should start lifelong antiretroviral therapy immediately.

For women with CD4 counts above 350, WHO recommends two options:

• Option A: AZT prophylaxis for the mother during pregnancy; single-dose nevirapine for mother and infant around delivery; AZT/3TC for the mother during delivery and for seven days afterwards; daily nevirapine for the infant until one week after breastfeeding ceases.
• Option B: Three-drug antiretroviral therapy from week 14 of pregnancy until the end of the breastfeeding period.

At a satellite meeting organised by the Elizabeth Glaser Pediatric AIDS Foundation, representatives of country programmes talked about the dilemmas they have faced in deciding how to adapt the guidelines to their national contexts.

In Zimbabwe, for example, the national AIDS programme has decided to provide nevirapine-based ART regimens to mothers with CD4 counts below 350, and has chosen option A as the more affordable route to reducing mother-to-child HIV transmission.

But the AIDS programme recognises that a lot of work will be needed to get everyone up to speed on the new guidance, and has been conducting extensive stakeholder consultations to make sure that everyone is happy with the new direction.

At the moment, almost 85% of sites providing PMTCT services in Zimbabwe are still employing single-dose nevirapine, and there is very limited capacity for ART initiation because antiretroviral therapy must be prescribed by doctors. The country also has only limited laboratory capacity to carry out CD4 cell monitoring, with few machines, unreliable supplies and a failure to communicate results.

But as well as HIV-specific problems, the AIDS programme also has to contend with some more fundamental weaknesses of the health system. There is high turnover of health care staff, which means a constant need for retraining to ensure that all staff understand the correct procedures for offering HIV tests, counselling and recording information, and administering drugs. Record-keeping remains a weakness, and there are problems in referral and follow-up of mothers with HIV and their infants.

Last, but not least, the recent introduction of user fees for the use of health facilities is likely to deter women from attending antenatal clinics.

In Kenya, the government is also planning to introduce Option A for mothers in less immediate need of ART for their own health, but similarly faces limited healthcare worker capacity and a shortage of CD4 counting machines.

In Malawi, said Dr Erik Schouten of the country's Ministry of Health, stakeholders had looked at the WHO guidance and tried to assess which option would be most realistic for the country’s health system to implement.

“The success of antiretroviral therapy in Malawi was based on a public health approach that acknowledges the realities of the health system’s capacity,” said Dr Schouten. That means limited use of CD4 counts, task-shifting to allow nurses to initiate and monitor ART, and devolution of care down to the local health centre.

Whilst incorporating treatment for all pregnant women below 350 presents no problem apart from cost, option A  for women with CD4 counts above 350 would prove challenging, he noted. It’s too complicated for health care workers to administer, requiring four separate stages of treatment for the mother, plus infant prophylaxis throughout breastfeeding. On average women in Malawi breastfeed for 23 months, according to Dr Schouten.

The CD4 count requirement is also a major challenge for the country where only 20% of people living with HIV presently have access to immunological monitoring. The country has about 50 CD4 counting machines, but their maintenance has proven so difficult that many of the machines haven’t produced results in months. Dr Schouten said that this is even the case in some of the larger cities in the country. Providing access to CD4 cell monitoring at antenatal clinics in the periphery would be even more challenging. Even if blood specimens were drawn, packaged and transported to a working laboratory, pregnant women would have to come back within a week or two for the results.  There is a chance that a significant proportion would not, and would fall through the cracks.

Dr Schouten said that these clinics generally only have one clinical officer and two nurses managing about 150 to 200 patients a day. Even if point-of-care CD4 cell tests were to become available, they would still take time to administer and read, straining clinics already operating past capacity. But the technology is not available to fill this gap at the moment, said Dr Schouten, and it’s unlikely to be developed for several years. 

So Malawi has decided to start all pregnant women with HIV on ART and to keep them on treatment for life. They call this 'Option B-Plus', and says Dr Schouten, it could offer several advantages:

• It protects the mother from the beginning of her next pregnancy as well.
• It could reduce maternal postpartum mortality and AIDS mortality (a retrospective review of the DREAM cohort – which included women with CD4 cells above 350  – presented at IAS last year found significantly lower maternal mortality among women more extensively treated with ART.
• It will reduce the risk of TB.
• It prevents maternal exposure to single-dose nevirapine, thus preventing resistance and preserving the mother’s treatment options.

As Professor Anthony Harries pointed out, Option B-Plus will depend on getting money from the Global Fund, but, said Dr Schouten, it’s the only realistic option for Malawi.

It’s clear that, as countries gear up to submit proposals for expansion of PMTCT programmes to the Global Found round 10 in late August, slightly different decisions are being reached in each country about how far to go in implementing WHO recommendations.

However, Malawi is the only country that appears to be pushing the envelope, and Professor Harries says that the Malawian approach will offer a major opportunity to assess the feasibility and acceptability of a staged introduction of 'universal test and treat', with pregnant women as the first group.

Mathematical modelling of the anticipated impact of the option A and B regimens discussed above has provided insight into their potential cost-effectiveness.

The mathematical modeling exercise, presented by Andrew Auld of the US Centers for Disease Control Global AIDS Program, found that while options A and B had similar PMTCT benefits, the first option was more cost-effective.

The model utilised data from twelve African countries and from Guyana, Haiti and Vietnam. It took into account HIV infection risk throughout pregnancy and breastfeeding, and both options included lifelong triple-drug treatment for all mothers with CD4 counts below 350 cells/mm³.

The two currently recommended PMTCT options appear to deliver considerably better outcomes than did the earlier WHO PMTCT protocol, albeit at higher costs.

Under the previous WHO guidelines, issued in 1996, an estimated 66,000 HIV infections per year would be averted with the recommended prophylaxis. The number of infections averted increases to 169,000 (95% CI, 116,000 to 187,000) with option A and 152,000 (95% CI 94,000 to 165,000) with option B.

Life-years gained in the three scenarios, with 3% annual discounting, were 1.3 million, 3.2 million and 2.9 million, respectively.

Total costs came to US$64 million, US$235 million and US$343 million respectively, with costs varying in the third scenario in accordance with the antiretrovirals used.

The incremental cost-effectiveness ratio (ICER) for the more cost-effective of the two recommended regimens was US$92 per life-year gained, placing it well within the cost-effectiveness range for low-income countries.

Auld AF et al. Potential impact and cost-effectiveness of the 2009 “rapid advice” PMTCT guidelines – 15 resource-limited countries, 2010. Eighteenth International AIDS Conference, Vienna, abstract WEAE0205, 2010.

Andrew Auld's presentation and the related abstract are available on the official conference website.

Dr Erik Schouten's presentation is available on the Elizabeth Glaser Pediatric AIDS Foundation website (PDF).