IAS: Low rates of HIV transmission in breastfeeding women on ART

Antiretroviral therapy (ART) appears to dramatically reduce the chances of breastfeeding women with HIV transmitting the virus to their infants, according to two studies presented on Tuesday at the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Sydney.

In the MITRA Plus trial from Tanzania, ART and breastfeeding was associated with a cumulative transmission at six months of only 5.0% (less than 1% had been infected during the period of breasfeeding). And in the AMATA study in Rwanda, only one out of 174 (0.6%) breastfeeding women on ART transmitted HIV to her infant — and since she had detectable viral load at the time, investigators believe that she may have discontinued her medication.

Breastfeeding quandary

Until now most large studies to prevent mother to child transmission (PMTCT) have concentrated on the effects of providing one, two or three-drug antiretroviral therapy around the time of delivery and during the immediate post-partum period.

But a child must be fed. However, when the mother is HIV-infected, breastfeeding carries a risk of transmitting the virus to her child — and undoing most of benefits of PMTCT. Up to one-third of HIV transmission from mother to infant takes place after childbirth, while the mother is feeding her infant with her breastmilk (and usually other foods).

Initial solutions focused on providing formula to the mother, but numerous operational studies show that while this may be practicable in a clinical trial, it is difficult to implement consistently and safely on a wide-scale in most resource limited settings.

“The majority of women in developing countries (including Tanzania) have to breastfeed their infants as they have no safe, acceptable or feasible alternative feeding options,” said Dr Charles Kilewo, of the Muhimbili University College of Health Sciences, in Dar es Salaam, Tanzania, who presented the MITRA findings.

Other studies have shown that exclusively breastfeeding rather than giving the babies mixed feeding (non-breast milk and solids which irritate the infant’s gut lining) significantly reduces the risk of HIV transmission. However, exclusive breastfeeding does not totally eliminate the risk of transmission.

Providing drug therapy that can reduce viral load in breast milk is complicated by the fact that breastmilk is a protected compartment within the body. It isn’t clear how well the antiretrovirals will penetrate and reduce viral load in the milk. Anything less than total suppression of the virus in the breastmilk could lead to resistance.

Some preliminary studies in breastfeeding mothers who are already eligible for ART for their own health have suggested that it reduces the risk of transmission. But for the wider population of HIV-positive mothers who don’t yet need antiretroviral therapy for their own health, the value of a limited period of triple drug therapy has been unproven – until now.

MITRA Plus

The MITRA Plus study was a non-randomised open-label study of the effects of triple antiretroviral therapy for mothers on HIV transmission to infants. Mothers received ART from late pregnancy (around week 34) and discontinued after the infant was six months old and breastfeeding stopped, unless the mother needed ART for her own health. Some mothers began ART earlier than week 34 if they had WHO Grade 3 or 4 HIV-related symptoms or a CD4 cell count below 200 cells/mm³. The vast majority (93.9%) had WHO stage 1 disease.

In this study, mothers received AZT/3TC plus nevirapine. Later, in women with CD4 cell counts above 250 cells/mm³, nevirapine was replaced by nelfinavir according to guidelines to prevent adverse reactions to nevirapine. Infants received AZT/3TC syrup for one week after birth.

Women were counselled on the importance of exclusive breastfeeding, and on the need for weaning after six months. The median period of breastfeeding was 24 weeks.

At week 6, 4.1% (95% confidence interval 2.0% - 6.0%) were already infected with HIV, as measured by DNA-PCR, suggesting that they may have been infected in the womb prior to the initiation of antiretroviral therapy, or during delivery.

But the study found that of 441 infants alive at six months of age, 5% had become infected with HIV. Of crucial importance, less than one in five of those infants had become infected between week 6 and 6 months of age, suggesting that antiretroviral therapy had proved highly protective during the breastfeeding period.

Dr Kilewo noted that this compared quite favourably to results of the Petra study (in which mothers did not receive antiretroviral therapy beyond one week after delivery). In the Petra study, a similar proportion of infants were infected at 6 weeks (5.4%), but at 6 months, 11.9% of the infants were infected.

AMATA

The AMATA study also investigated the effects of antiretroviral therapy on HIV transmission during the breastfeeding period, but had a slightly different design.

In this study, carried out in Kigali, Rwanda, all HIV-positive women at four antenatal care sites were offered the option of participating in the study.

Women were then asked to choose whether to breastfeed exclusively or whether to adopt formula feeding. All mothers received antiretroviral therapy from the beginning of the third trimester of pregnancy.

The study enrolled 572 women, and 554 live births had been reported by July 200, 316 (57%) formula fed, and 238 (43%) breastfed with ART. So far, DNA-PCR test results are available for 484 (90%) infants at six weeks of age and 431 (87%) at 7 months of age.

At childbirth, viral loads were undetectable in 52% of the mothers, between 40-1000 copies/ml in 38% and above 1000 copies/ml in only 10%.

Seven children have been found to be HIV-infected, six at birth, and only one infection occurred during the breastfeeding period.

In this latter case, the mother had undetectable viral load at childbirth, but had a viral load of 4,000 copies/ml at weaning. She is believed to have quit taking her medications, according to Dr Vic Arendt of the Centre Hospitalier de Luxembourg, which worked with the Centre Hospitalier Universitaire de Kigali, on the study.

Another interesting finding is that no statistically significant differences in mortality or morbidity were observed despite findings from other studies showing that infants of HIV-positive mothers who were breastfed had lower rates of illness and death than formula-fed infants.

Formula fed infants often have health problems in resource-limited settings (diarrhoea and chest infections). In this study, a little over a third of the infants in both arms needed to make medical visits, and only 10% of the infants who were formula fed were hospitalised due to illness, compared to 6% of those who were breastfed (p=0.17). Children who were breastfed did gain weight faster, though this levelled off a bit at the time of weaning.

Of the 24 children who died, 6 (3%) were in the breastfeeding arm, versus 18 (6%) in the formula feeding arm (p=0.15), which may suggest a slight trend that could become significant if the study were larger.

However, other studies in Rwanda of formula fed infants reported at the Implementers Meeting in Kigali Rwanda, also reported low rates of morbidity and mortality among formula fed infants. Several researchers noted, though, that mothers and children in these studies had exceptional access to health services — and were quick to utilise them if they saw any sign of illness in their child.