Elsevier

The Lancet

Volume 353, Issue 9155, 6 March 1999, Pages 832-835
The Lancet

Consensus Statement
Science, ethics, and the future of research into maternal infant transmission of HIV-1

https://doi.org/10.1016/S0140-6736(98)10414-2Get rights and content

Summary

Effective, feasible interventions to prevent perinatal transmission of HIV-1 in developing nations are an urgent necessity. Scientific issues of concern include a need to identify other effective antiretroviral agents; to define the shortest effective course of therapy; to assess interventions other than antiretroviral agents; and to investigate interventions that may reduce HIV-1 transmission via breastfeeding. Sound scientific design is fundamental to all research studies. Ethical standards must guide such studies and include the necessity that the problem studied be a health priority in the host country; that the highest standard of care attainable in the country be assured to participants; that the health-care resources of the country not be harmed; that the informed consent of participants be obtained; and that a process of discussion ensure that a successful intervention will be considered for implementation. There are circumstances in which a no-antiretroviral comparison may be ethically justified.

Introduction

The Elizabeth Glaser Pediatric AIDS Foundation and the Emory/Atlanta Center for AIDS Research convened a workshop entitled Perinantal HIV Intervention Research in Developing Countries: Public Health, Science, and Ethics on June 9–10, 1998, at the Rollins School of Public Health at Emory University, USA, in response to controversy over perinatal interventions. We, the workshop participants, committed ourselves individually to encouraging ethical research on reducing perinatal HIV-1 transmission that is tailored to the specific needs of specific communities, and that is fully responsive to the economic, medical, and social context of those communities. Effective and affordable interventions to prevent perinatal transmission in developing nations are an urgent necessity because these nations sustain the vast majority of all paediatric HIV-1 infections. In the USA, there have been more than 8000 reported cases of paediatric AIDS1 and more than 15 000 estimated paediatric HIV-1 infections.2 However, WHO estimates that there are roughly 1600 children infected with HIV-1 every day or about 600 000 new infections annually in children throughout the world, 90% of which occur in developing countries.3

There was a 43% decrease in reported paediatric AIDS cases in the USA from 1992 to 1996,4 probably owing to the establishment of a standard of care in the USA that stresses HIV-1 counselling and testing for all pregnant women, the provision of a regimen of zidovudine (ZDV) for HIV-1-infected pregnant women,5 and careful obstetrical management. In addition, fewer HIV-1-positive women are giving birth in some areas. The threepart ZDV prophylaxis regimen (named for the Pediatric AIDS Clinical Trials Group [PACTG] 076 study, which established its efficacy) includes oral ZDV started after 14 weeks' gestation, intravenous ZDV during labour and delivery, and ZDV syrup for the infant for 6 weeks after delivery.6 ZDV decreased HIV-1 RNA concentrations by only 0·2 log in the PACTG 076 study. Nevertheless, the 076 ZDV regimen diminished transmission by 68% in the PACTG 076 study, and decreased rates to less than 5–8% among women and infants in multiple observational studies7, 8, 9 and in a secondary randomised trial.10 Furthermore, the results of a trial11 in Thailand announced in February, 1998, showed that a short course of ZDV, administered orally for the last 4 weeks of gestation and orally during labour and delivery, diminished HIV-1 transmission by 51% to infants who were not breastfeeding. The cost of ZDV is far less than the three-part PACTG 076 regiman, and the two-part regimen is simpler to administer. The costs of counselling and testing are still incurred, since the drug is only given to pregnant women known to be infected with HIV-1. Neither of these regimens seems to have any serious short-term side-effects on the women or their infants in follow-up for as long as 6 years.12 The long-term effects are unknown and under study.

Section snippets

Need for research

The success that the 076 and Thai ZDV regimens have shown in limiting perinatal HIV-1 transmission means that all countries are encouraged to review these available proven interventions and to make every effort to implement them. Although the Thai regimen provides an affordable, feasible intervention for some developing countries, participants at this workshop were concerned that numerous factors inhibit the adoption of this regimen in other developing nations. First, although the cost of the

Scientific questions

We agreed that eliminating the substantial gap between the practical requirements for implementation of the only two regimens proven to diminish HIV-1 perinatal transmission and the economic, medical, and social realities of developing nations must occur if perinatal HIV-1 infection is to be controlled worldwide. This agreement led us to a consensus that the findings from the CDC/Thailand study—while encouraging and implementable in some settings—do not eliminate the need to identify new,

Ethical principles

Following the CIOMS/WHO International Ethical Guidelines for Biomedical Research Involving Human Subjects, we also agreed that sound scientific design is a fundamental ethical principle of all research studies, and that appropriate ethical standards must guide such studies.15, 16, 17, 18, 19, 20 Based on these international guidelines, we endorsed the following five ethical principles. First, the problem under study should be a health priority established by the public-health officials in the

Design of scientific studies

We agreed that scientific questions are the primary determinants of study design. Equivalency design (a comparison of two interventions) and superiority design (a comparison of an intervention to an untreated group receiving the highest standard of care practically attainable in the host country) answer different questions. The selection of study design (equivalency or superiority design) was discussed, and we decided that this choice must take into account the circumstances and population of

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