PREVENTION PREVENTINGMOTHER-TO-CHILD TRANSMISSION OF HN African Solutions for an African Crisis

James McIntyre, MRCOG, Glenda Gray, MB ChB, FCPaeds (SA) Perinatal HIV Research Unit, University ofthe WiruJafersrmzd and Clzris Hani Baragwanath Hospital. Johannesburg 'I am convinced that our urgent task is to respond to the specific threat that faces us as Africans.' President Thabo Mbekj' The issue of mother-to-child transmission (MTCT) of HIV has become increasingly politicised in , with accusations and counter-accusations from all sides. Oinicians and activists, unable to comprehend the government's decisions not to provide inexpensive treatment to prevent MTCT, accuse it of child murder, while the President and Minister of Health claim concern about the safety of the drugs and make sweeping statements about mothers being killed. Amid all the political noise, scientific findings seem to be forgotten. The South African President has called for a 'search for specific and targeted responses to the specifically African incidence of HIV-AIDS',' but it appears that some of the evidence already collected by African scientists and their collaborators, with the participation of African women and children, has been ignored. HIV seroprevalence in pregnant women in South Africa averages 23%, rising to 33% in the worst-hit provinces. Some South African studies' have reported MTCT rates of over 35% in the absence of any intervention and where breast-feeding is practised. With a conservative estimate of 800 000 births per year in South Africa, this suggests 70000 infants are affected annually. The head of the Medical Research Council, Professor Malegapuru Makgoba, wrote in a recent Science editorial' that the decision not to use antiretrovirals for the prevention of MTCT 'poses serious moral and ethical dilemmas in a nation where maternal-fetal transmission of HlV accounts annually for 10% of the total HlV disease burden'. The need for an effective and affordable strategy to reduce MTCT of HlV is a matter of urgency.

ANTIRETROVIRAL THERAPY duction in MTCT" Asecond random-ised placebo. Arm A received ZDV and 3TC trial of the ZDV regimen was conducted from 36 weeks' gestation} during labour The use of antiretroviral treatment during in 260 women in C5te d'Ivoire. This and for 1 week postpartum (mother and pregnancy has resulted in a dramatic resulted in a 37% reduction in trans­ child). Arm B received ZDV and 3TC decline in the number of perinatal HIV mission in the treatment group by the from the onset of labour and for 1 week infections in the USA and Europe. time the infants were 3 months of age." postpartum (mother and childl. Arm C Transmission rates in Los Angeles have In contrast to the Thai study, over 95% received ZDV and 3TC during labour dropped from 30% to 10%, and in North of the infants in the C5te d'Ivoire trial only. Interim early efficacy results have Carolina from 21 % to 8.5%.4 Reported were breast-fed. been reported, showing that the risk of transmission rates in the USA and France Another trial of short-eourse ZOV transmission by 6 weeks of age was 8.6% declined by between one-half and two­ was conducted among 350 women in in arm A, 10.8% in arm 8/ 17.7% in thirds within the first 3 years of routine Burkina Faso and C5te d'Ivoire. The trial arm Cand 17.2% in the placebo group." use of (ZDV) in pregnancy.'·' com-pared placebo with oral ZDV is a fast-acting and potent Further reductions have been seen, with started at between 36 and 38 weeks' antiretroviral, with a long half-life. The transmission rates of less than 5% now gestation at 300 mg twice daily. This was HIVNET 012 trial in Uganda" invest­ recorded.' Astudy in France" showed that followed by a single loading dose of 600 igated the use of a single 200 mg dose of HIV-positive women who received this mg at the onset of labour and oral ZDV nevirapine administered orally to women ZDV regimen and who had an elective 300 mg administered to mothers twice at the onset of labour and a single dose caesarean section had a transmission rate daily for 7 days after delivery. In this trial of 2 mg/kg administered to infants with­ of 0.8%. over 85% of infants were breast-fed for in 72 hours of birth, compared with When the results of the PACTG 076 longer than 3 months. The efficacy of intrapartum ZDV and 1 week of infant trial became available in 1994,' it was ZDV was estimated at 38% (95% ZDV treatment. Almost all babies were obvious that the expensive regimen confidence intervals (Cl) 5% - 60%) breast-fed. In the nevirapine treatment would not be feasible in most developing when infants were 6 months of age,lZ and group the transmission rate at 14 - 16 countries in the short term. African and at 30% when they were 15 months old." weeks was 13.1 % compared with 25.1 % in the comparison group. The efficacy of Asian scientistsl with international col­ The PET RA study, " conducted in five laborators, commenced a series of trials African sites in South Africa, Tanzania nevirapine was 47% (95% Cl 20 - 64l. to investigate the efficacy of shorHourse and Uganda, investigated different Side-effects were similar for the antiretroviral therapy in late pregnancy. regimens of a combination of ZDV and two regimens, both of which were well The first trial results, from Thailand, 3TC (Iamivudine) in over 1 700 women. tolerated." The South African Intra­ demonstrated that 4 weeks of ZDV given This trial compared the effectiveness partum Nevirapine Trial (SAINT) is in late pregnancy produced a 50% re- of three different drug regimens with investigating intrapartum and postpartum

JULY 2000------TH£ SOUTHtRN AFRICAN JOURNAL Of HIV M£OICIN£ nevirapine compared with the arm B in exclusively breast and formula-fed REFERENCES reqimen from the PETRA study, with infants were simila~ while infants who 1. Anonymous. South African President addresses AIDS in Africa. Washington Post. Iq April 2000. results expected in mid-2000. received mixed feeding had higher rates of 2. Bobat R, Moodley D, Coutsoudis A, Coovadia H. These trials of antiretroviral inter­ infection. These findings are interesting Breastfeeding by HIV-l-infected women and out­ come in their infantS: a cohort study from Durban, ventions have included several thousand and require further investigation in a South Africa AIDS lqq7; 11: 1627-1633. African mother-infant pairs. To date, none larger trial. 3. Makgoba MW. HIVlAIDS: The pedl of pseudo­ science (Editorial). Science 2000; 288: non. of these trials has demonstrated signi­ 4. Fiscus SA, Adimora AA, Schoenbach VJ, et al. ficant toxicity or serious side-effects in ONGOING RESEARCH Perinatal HIV infection and the effect of zido­ vudine therapy on transmission in rural and urban mothers or infants. A small study in Several ongoing studies in Africa will counties. JAMA lq96; 275: 1483-1488. Uganda" has demonstrated the devel­ 5. Simonds RJ, Ste etee R, Nesheim S, et af. add to our knowledge of prevention Impact of zidovudine use on risk and risk factDrs opment of a nevirapine-resistant virus in strateqies. In Malawi, a trial of treat­ for perinatal transmission of HIV. Perinatal AIDS 3 of 14 women who received only one Collaborative Transmission Studies. AIDS lqq8; ment for chorioamnionitis and sexually 12: 301~308. intrapartum dose of nevirapine. Further transmitted infections in pregnancy is 6. MayaLlx MJ, Teglas JP, Mandelbrot L, er al. studies on the development of resistance Accept.ability and impact of zidavudine for underway. A study in is assessing prevention of mother-tO

THf SOUTHfRN AfRICAN JOURNAL OF HIV MfDlCINf ------JULY 2000