Impact of antiretroviral PMTCT prophylaxis regimens on subsequent maternal disease progression in Kesho Bora

26 August 2010. Related: Conference reports, Antiretrovirals, Pregnancy, World AIDS 18 Vienna 2010.

Polly Clayden, HIV i-Base

HAART regimens used as prophylaxis during pregnancy and breastfeeding are effective in reducing mother to child transmission and are standard of care in industrialised countries.

There are some concerns, particularly since the results from the SMART study, that stopping HAART prophylaxis at the end of breastfeeding may have adverse effects on maternal health and survival.

The Kesho Bora study randomised pregnant women with CD4 counts 200-500 cells/mm3 at 28-36 weeks of pregnancy, to receive either maternal HAART (zidovudine + lamivudine + lopinavir/ritonavir to six months after delivery or breastfeeding cessation if earlier) or short- course zidovudine plus single-dose nevirapine in labour. All infants received single-dose nevirapine post partum. The results, presented at the IAS conference last year (and reported in the August 2009 edition of HTB) showed HIV transmission rates to be almost identical. [1, 2]

These data also contributed to the evidence that enabled the WHO to recommend that HIV-positive mothers or their infants take antiretrovirals while breastfeeding to prevent mother-to child transmission.

In an oral late breaker, Tim Farley presented findings from an evaluation of maternal HIV disease progression at 18-24 months post delivery. [3]

Disease progression endpoints were stage 4 or CD4 <200 cells/mm3 and stage 3 or CD4 <350 cells/mm3. These represent previous and current WHO thresholds for initiating antiretroviral treatment.

There were 412 women in each arm, who had received prophylaxis for a median of 6 weeks before delivery. Women receiving HAART received it for a median of 19 additional weeks during breastfeeding.

The investigators found lower rates of progression to stage 4 or CD4 200 cells/mm3 among women receiving HAART at all time points from delivery when all women were included in the analysis, p=0.003. See Table 1. But rates were similar after stopping antiretroviral prophylaxis, p=0.159. See Table 2.

They performed the same analysis censoring women with CD4 >350 cells/mm3 and there was a significant difference in progression rate from delivery, p=0.002, and no difference from stopping prophylaxis, p=0.107. See Tables 3 and 4.

A further analysis was performed looking at rates of progression to stage 3 or CD4 <350 cells/mm3 among women with CD4 >350 cells at entry. This gave differences of p=0.002 and p=0.013 from delivery and stopping prophylaxis respectively. See Tables 5 and 6.

Overall the investigators concluded that receiving maternal HAART as prophylaxis and stopping after breastfeeding did no harm compared to short course zidovudine plus single dose nevirapine. In the discussion following the presentation it was suggested that the conclusion that this strategy did “no harm” was difficult to make without having included an arm in which treatment was continued. Dr Farley agreed that this was also an important question but the study design reflects an era when even using HAART and continuing it through breastfeeding in healthier women was considered quite radical in resource limited settings.

The other important conclusion from the analysis is that the high rate of progression to CD4 <200 cells/mm3 in both arms among women with <350 cells/mm3 at entry, reinforces WHO guidance to treat from 350 cells/mm3 and emphasises the importance of early treatment initiation in pregnant women or women desiring pregnancy.

References:

1. Farley T and The Kesho Bora Study Group. Impact of triple ARV prophylaxis during pregnancy and breastfeeding compared with short-ARV prophylaxis for MTCT prevention on maternal disease progression. 18th IAS Conference, 18–23 July 2010, Vienna. Oral abstract ThLBB105. http://pag.aids2010.org/Abstracts.aspx?SID=644&AID=17446
2. Clayden P. Reducing HIV transmission during breastfeeding. HIV Treatment Bulletin, August 2009. https://i-base.info/htb/4466