HIV This Week

Rollins N, Little K, Mzolo S, Horwood C, Newell ML. Surveillance of mother-to-child transmission prevention programmes at immunization clinics: the case for universal screening. Rev Med Virol. 2007 Jun 1; [Epub ahead of print]

Surveillance programmes for prevention of mother-to-child transmission of HIV (PMTCT) fail to quantify numbers of infant HIV infections averted, often because of poor postnatal follow-up. Additionally, infected infants are often not identified early and only gain access to comprehensive HIV care and treatment late in their disease. Rollins et al conducted anonymous, unlinked, HIV prevalence testing on dried blood spot (DBS) samples from all infants attending 6 week immunization clinics at seven primary health care clinics offering PMTCT. Samples were tested for HIV antibodies (indicating maternal HIV infection) and those determined to be from HIV-exposed infants were tested for HIV RNA by polymerase chain reaction. Infant and child mortality rates were determined using birth histories. The authors collected samples from 2489 infants aged 4-8 weeks. HIV antibodies were identified in 931 infants [37.4%; 95% confidence interval (CI), 35.4-39.4], of whom 188 were HIV RNA positive. The estimated vertical transmission rate (VTR) was 20.2% (95% CI, 17.8-23.1%); 7.5% of all infants at this age were infected. Amongst mothers who reported that they had taken single-dose nevirapine for PMTCT, VTR was 15.0%. Amongst women who reported being HIV uninfected but whose infants had HIV antibodies, VTR was 30.5%. Infant mortality rates in KwaZulu Natal increased from 28/1000 live births in 1990-1994 to 92/1000 in 2000-2004. Anonymous HIV prevalence screening of all infants at immunization clinics is feasible to monitor the impact of PMTCT programmes on peri-partum infection; linked screening could identify infected children early for referral into care and treatment programmes.

Editors’ note: This surveillance programme using anonymous unlinked testing is not only a good programme measurement tool but revealed higher transmission rates among women who did not believe they were infected. Conducting in-depth interviews and focus groups with clinic attendees based on this information would help to develop effective communication messages to encourage pregnant women in this high prevalence setting to consider HIV testing more seriously. 

In the absence of interventions, 30-45% of exposed infants acquire human immunodeficiency virus type 1 (HIV-1) through mother-to-child transmission. It remains unclear why some infants become infected while others do not, despite significant exposure to HIV-1 in utero, during delivery and while breastfeeding. Here we discuss the correlates of vertical transmission with an emphasis on factors that increase maternal HIV-1 levels, either systemically or locally in genital secretions and breast milk. Immune responses may influence maternal viral load, and data suggest that maternal neutralising antibodies reduce infection rates. In addition, infants may be capable of mounting HIV-specific cellular immune responses. We propose that both humoral and cellular responses are necessary to reduce infection because cell-free as well as cell-associated virus appears to play a role in vertical transmission. These distinct forms of the virus may be targeted most effectively by different components of the immune system. We also discuss the use of antiretrovirals to reduce transmission, focusing on the mechanisms of action of regimens currently used in developing country settings. We conclude that prevention relies not only on reducing maternal HIV-1 levels within blood, genital tract and breast milk, but also on pre- and/or post-exposure prophylaxis to the infant. However, HIV-1 has the capacity to mutate under drug pressure and rapidly acquires mutations conferring antiretroviral resistance. This review concludes with data on persistence of low-level resistance after delivery as well as recent guidelines for maternal and infant regimens designed to limit resistance. Copyright (c) 2007 John Wiley & Sons, Ltd.

Editors’ note: This review highlights the need for drugs that work to both reduce viral load in the mother and mop up any HIV that slips through to the baby.

Up to 40% of all mother-to-child transmission of HIV occurs by means of breast-feeding; yet, in developing countries, infant formula may not be a safe option. The World Health Organization recommends heat-treated breast milk as an infant-feeding alternative. Israel-Ballard and colleagues investigated the ability of a simple method, flash-heat, to inactivate HIV in breast milk from HIV-positive mothers. Ninety-eight breast milk samples, collected from 84 HIV-positive mothers in a periurban settlement in South Africa, were aliquoted to unheated control and flash-heating. Reverse transcriptase (RT) assays (lower detection limit of 400 HIV copies/mL) were performed to differentiate active versus inactivated cell-free HIV in unheated and flash-heated samples. The authors found detectable HIV in breast milk samples from 31% (26 of 84) of mothers. After adjusting for covariates, multivariate logistic regression showed a statistically significant negative association between detectable virus in breast milk and maternal CD4T-lymphocyte count (P = 0.045) and volume of breast milk expressed (P = 0.01) and a positive association with use of multivitamins (P = 0.03). All flash-heated samples showed undetectable levels of cell-free HIV-1 as detected by the RT assay (P< 0.00001). The authors conclude that flash-heat can inactivate HIV in naturally infected breast milk from HIV-positive women. Field studies are urgently needed to determine the feasibility of in-home flash-heating breast milk to improve infant health while reducing postnatal transmission of HIV in developing countries.

Editors’ note: Direct boiling of breast milk causes significant nutritional damage while standard pasteurization for 30 minutes requires temperature gauges and timing devices that are unavailable in many communities. Flash-heat is a recently developed, simple method that a mother can implement over an outdoor fire or in her kitchen. She expresses about 50 ml of breast milk into a locally available clean bottle and places it in a pot with warm water. As soon as the water comes to a rolling boil (100C) the bottle is removed and allowed to cool. This pilot study found the flash-heat method was capable of inactivating cell-free clade C HIV-1 while retaining most of the milk’s nutritional and antimicrobial properties. The next step: from the laboratory to field testing.