PEPI-Malawi

26 April 2009. Related: Conference reports, Pregnancy, CROI 16 (Retrovirus) 2009.

Polly Clayden, HIV i-Base

Taha Taha presented data from the PEPI (Post Exposure Prophlaxis of Infants) trial, conducted in Malawi, evaluating the effect of maternal HAART on postnatal transmission following cessation of extended infant antiretroviral prophylaxis. [1]

In the PEPI trial, all mothers received single dose nevirapine (NVP) in labour and uninfected infants were randomised to receive either: one week AZT (control arm); control plus daily NVP to infants for 14 weeks, or control plus daily NVP and AZT to infants for 14 weeks. (These findings were presented at CROI last year and reported in HTB). [2, 3]

The trial demonstrated that extended infant prophylaxis from birth to 14 weeks reduced breast-feeding transmission by >65% during the time of prophylaxis. However, this effect diminished over time.

The investigators then examined the association between maternal HAART use and postnatal transmission after cessation of infant prophylaxis. Dr Taha noted that when PEPI began in 2004, HAART was not available in Malawi but while the trial was being conducted it became available in 2006 through the government programme.

Eligible women (with clinical indication and/or CD4 >250 cells/mm3) were referred to the antiretroviral treatment clinic. Dr Taha reported that this was not without logistical problems and some women did not receive HAART due to clinic waiting time; missed visits; delays with drug availability; partner consent and refusals. Overall coverage was limited, with only 13% women receiving HAART during follow up and >80% of those initiated it >14 weeks post partum.

The investigators defined three groups of women for evaluation: eligible women receiving HAART; eligible women untreated and ineligible women. Infant infection rates were calculated using Kaplan-Meir estimates and person time contributed by infants stratified by maternal HAART category. Hazard ratios were calculated adjusting for infant prophylaxis arm.

A total of 2318 infants uninfected at 14 weeks were included (representing 2750 person years of follow up). The majority of infants, 73% (1694), had mothers with high CD4 count for the duration of follow up; the remainder had mothers with low CD4 count. Of this group, 5.6% (133) had high CD4 count early, which declined to <250 cells/mm3 during follow up and 21% (491) had low CD4 throughout follow up. 310 women received HAART at sometime post partum: 45% (279/624) with low CD4 and 2% (31/1694) with clinical indication.

130 (5.6%) infants became infected during follow up. Of these, 5 infants had mothers receiving HAART (279 person years of follow up); 53 had eligible but untreated mothers (502 person years of follow up) and 72 infants had ineligible mothers (1969 person years of follow up).

The cumulative HIV infections among infants, uninfected at 14 weeks, at 6 months were 1.3% (95% CI, 0.7-2.5%), 0.9% (95% CI, 0.4-1.9%) and 1.8% (95% CI,1.1-3.1%) in the control (n=722), extended NVP (n=804) and extended NVP plus AZT (n=792) arms respectively. This increased by approximately 1-2% every 3 months, rising to 6.9% (95% CI, 5.0-9.4%), 8.2% (95% CI, 6.1-11.1%) and 7.9% (95% CI, 5.9-10.4%) cumulative infections at 24 weeks in the in the control, extended NVP and extended NVP plus AZT arms respectively. At no time point during follow up did the difference in study arms reach statistical significance.

When the investigators looked at the association between HIV transmission and maternal HAART use they found that HAART use in eligible women was associated with a significant transmission reduction of 82% compared to untreated women. Additionally being ineligible for HAART (73% of mothers) was associated with a 65% reduction in transmission. (See Table 1).

Table 1. Post natal HIV transmission (between 14 weeks and 24 months) and association with maternal HAART use

*Adjusted for infant prophylaxis study arm

The investigators concluded that an effective strategy for late presenting mothers in order to prolong safer breastfeeding would be:

• Starting extended infant prophylaxis at birth
• Rapid identification of women with low CD4 counts and fast initiation of HAART
• Continuing infant prophylaxis for women ineligible for HAART.

Comment

The limited coverage among women referred for HAART in this study is notablble. Jeff Stringer provided an excellent overview of prevention of breast-feeding transmission in the Wednesday plenary at this conference. [4]

References:

1. Taha T et al. Effect of maternal HAART on postnatal HIV-1 transmission after cessation of extended Infant Antiretroviral Prophylaxis. 16th CROI, Montreal, 2009. Abstract 92.
2. Taha T et al. Extended infant post-exposure prophylaxis with antiretroviral drugs significantly reduces postnatal HIV transmission: The PEPI-Malawi Study. 16th CROI, Montreal, 2009. Oral abstract 42LB
3. http://www.i-base.info/htb/v9/htb9-3-4/Infant.html
4. http://www.retroconference.org/2009/data/files/webcast.htm