18-month effectiveness of short-course perinatal antiretroviral regimens combined to infant-feeding interventions for PMTCT in DITRAME PLUS ANRS 1201/1202 2001-2005

7 October 2006. Related: Conference reports, Pregnancy, World AIDS 16 Toronto 2006.

Polly Clayden, HIV i-Base

Valeriane Leroy presented findings from a recent analysis of the ANRS 1201/1202 DITRAME PLUS study – that has looked at pre-, peri- and post-natal antiretroviral regimens for prevention of mother to child transmission (PMTCT) of HIV in Abidjan, Cote d’Ivoire – to assess the 18-month effectiveness of two short-course antiretroviral regimens combined with infant-feeding options. [1]

This sub study included women/infant pairs enrolled in DITRAME PLUS 1201, conducted between 2001-2002, (n=375) and DITRAME PLUS 1202 between 2002-2003 (n=336). In the 1201 study, women received AZT from 36 weeks gestation and single dose nevirapine (SD NVP) at delivery, and the infants SD NVP and AZT for 7 days. In the 1202 study, women received AZT+3TC from 32 weeks, SD NVP and AZT+3TC for three days post partum and the infants received SD NVP and AZT for 7 days.

Women were given the choice between formula feeding, with formula and equipment provided free of charge for 9 months (n=195 and n=126 in DITRAME PLUS 1201 and 1202 respectively), or exclusive short-term breastfeeding with early cessation from four months (n=169 and n=198 in DITRAME PLUS 1201 and 1202 respectively).

Follow up of mother infant pairs was over two years in two clinics. Blood samples for HIV diagnosis were taken at day 2, week 4-6, month 3 and then quarterly until 18 months or two months after breastfeeding cessation.

The investigators defined paediatric HIV infection as a positive PCR at any age, or if aged >18 months, a positive HIV serology. Postnatal transmission (PT) was defined as a child with a negative PCR from a sample obtained at >4weeks who later became infected. Cumulative transmission risks (CTRs) of infection were estimated using Turnbull method in each infant-feeding group defined at day 2.

The ANRS 049a DITRAME study conducted between 1995 and 1999 – in which women received short course AZT from 36 weeks gestation until delivery, followed by unrestricted breastfeeding – was used as the reference cohort (n=238).

Overall, the study population was broadly similar across the regimen and feeding option groups, but 15.5% of women were eligible for HAART in the reference group vs 24.6%, 31.8 (in 1201), 20.3 and 20.6 (in 1202) in the breast feeding and formula feeding groups respectively.

The investigators found that 107/926 infants (for whom 18 months CTR data were available) were HIV infected, of whom 27 were PT cases. There were 15 (22%, 95% CI: 16-30%) in the reference group, 10 (16%. 95% CI: 10-27%) in the 1201 breast fed group, 1 (9%. 95% CI: 6-14%) in the 1201 formula fed group, 1 (7%, 95%CI: 4-11%) in the 1202 breast fed group and 0 (6%. 95%CI: 2-10%).

In a multivariate model adjusted for maternal HAART eligibility, home delivery and low birth weight (2.5kg), the investigators found that both 1201 and 1202 groups had lower CTR than the reference cohort.

Table 1: Correlates of 18 month infection with DITRAME Plus – Multivariate model

Only treatment regimen, length of prophylaxis and maternal viral load were predictive of infant infection (see Table 1).

Dr Leroy concluded that peripartum short course regimens, combined with infant feeding interventions, significantly reduce MTCT compared to short course AZT in a long-term breastfeeding population. Both formula feeding and short-term breastfeeding were protective, but there was no significant protective effect of formula feeding compared to short term breast feeing.

She noted that the most effective of these strategies could result in 18 month TR as low as 6%.

Comment

These results are similar to the French cohort experience of adding 3TC at 32 weeks gestation to AZT. This was also very effective at reducing MTCT but associated with high rates of 3TC resistance. [2]

Although just failing to reach statistical signficance (95% CI crossing 1 [0.35-1.04]) formula-feeding was associated with a biologically significant reduction in the risk of transmission (adjusted hazard ratio 0.6) compared with weaning at 4 months.

References:

1. Leroy V, Ekouévi D.K., Dequae-Merchadou L et al. 18-month effectiveness of short-course perinatal antiretroviral regimens combined to infant-feeding interventions for PMTCT in Abidjan, Cote d’Ivoire. DITRAME PLUS ANRS 1201/1202 2001-2005. XVI International AIDS Conference, Toronto, Canada. 13 – 18 August 2006. Oral abstract THAC0101.
2. Mandelbrot L. et al. Lamivudine-Zidovudine combination for prevention of maternal-infant transmission of HIV-1. JAMA 2001;285:2083-93.