Unnecessary Deaths in South African HIV-Infected Infants

Is it ethical to use children in research studies to prove what is already known? Just how much proof is needed to act on scientific evidence that antiretroviral treatment is effective in preventing HIV disease progression and preventing death? http://treatall.org/

In 2005, a study of early versus delay treatment of HIV infected infants was initiated in South Africa. The study was called the “Children with HIV Early Antiretroviral Therapy” (CHER) study.  The primary purpose of the study was to determine the effect of delaying treatment in HIV infected infants compared to infants who were immediately placed on antiretroviral therapy (ART).  The rationale was based on the false hypothesis that infants and children respond differently to ART than adults.  In order to move ahead with the CHER study research physicians and internal review boards from both developed and developing countries had to engage in a form of scientific nihilism – dismissing convincing study results that showed that early antiretroviral treatment (ART) halted HIV disease progression and prevented death. They also overrode the objections of advocates and scientists that the study was unethical.

The CHER researchers placed vulnerable child at risk for early death— the results of the study were predictable—delayed treatment resulted in 4 times greater deaths—16% in the delayed treatment group vs 4% in those who were treated immediately after diagnosis. Fortunately, the Data and Safety Monitoring Board (DSMB) stopped the study after only 32 weeks of follow-up and called for initiating immediate treatment of all infants whose treatment had been delayed.

Why was the study done and why was it unethical? Prior to initiating the study there was abundant evidence from the treatment of HIV as well as other infectious diseases that delaying treatment in a deadly disease is of no benefit.  Further, decades previously the FDA, confronted with delays in the treatment of infants with HIV infection, had declared that it was unnecessary to study an effective antiretroviral drug in the pediatric population if the drug had been shown to be effective in an adult population. Tragically it was also known when the CHER study was designed that without treatment, HIV-infected infants die 4 to 5 times more quickly than adults; 30% die by one year of age and 50% die by two years of age.

Incredulously the study was supported by the US National Institutes of Health. It could never have been conducted in the US. What was unsettling about conducting the study in South Africa was, that in spite of South Africa experiencing one of the most rapid expansions of HIV infection in all of Africa, the country had for years been the victim of HIV denialism by its former president Mbeki that resulted in fatal delays in ART. During that time the majority of South African physicians and researchers pleaded that drugs should be made available to treat HIV-infected adults and children. Conducting the CHER study of withholding treatment from HIV infected infants when ART was at last available represented an incomprehensible paradox. Placing vulnerable infants at risk to satisfy an intellectual exercise of repeating a study to prove what was already known represents a weakening of ethical standards that protect children from exploitation. Perhaps the ethical standards which guide the conduct of studies in infants and children in the US are considered irrelevant when studies are conducted in resource poor countries.

References

1- Antiretroviral therapy initiated before 12 weeks of age reduces early mortality in young HIV-infected infants: evidence from the Children with HIV Early Antiretroviral Therapy (CHER) study. Violari A et al. Fourth International AIDS Society Conference on HIV Treatment and Pathogenesis, Sydney, abstract WESS103, 2007.

2- http://www3.niaid.nih.gov/news/QA/CHER_QA.htm

3- Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies. When To Start Consortium, Sterne JA, May M, Costagliola D, de Wolf F, Phillips AN, Harris R, Funk MJ, Geskus RB, Gill J, Dabis F, Miró JM, Justice AC, Ledergerber B, Fätkenheuer G, Hogg RS, Monforte AD, Saag M, Smith C, Staszewski S, Egger M, Cole SR. Lancet. 2009 Apr 18;373(9672):1352-63. doi: 10.1016/S0140-6736(09)60612-7.

4- Early antiretroviral therapy and mortality among HIV-infected infants. Violari A, Cotton MF, Gibb DM, Babiker AG, Steyn J, Madhi SA, Jean-Philippe P, McIntyre JA; CHER Study Team.N Engl J Med. 2008 Nov 20;359(21):2233-44.