joseph wright web

 

 

 

 

On February 21, 1994 New York Times science writer Lawrence Altman wrote a momentous article titled, “In Major Finding, Drug Curbs H.I.V. Infection in Newborns.” He was referring to a study of the drug zidovudine which had been given to HIV-infected pregnant women and their infants and was found to reduce HIV transmission by 60%. It was the first time in history the AIDS epidemic that a drug was shown to prevent HIV transmission from one infected individual to an uninfected individual. The stage was set for additional groundbreaking studies.

Almost two decades later it was demonstrated that potent antiretroviral drug combinations (HAART) could prevent HIV transmission between sexual partners. The discovery had the potential to dramatically reducing the number of new HIV infections world-wide. Equally momentous news for HIV infected women could have continued after the 1994 results on the reduction of HIV transmission from infected mothers to their infants—but it did not. In the decades that followed millions of infant lives could have been saved from HIV and the health of millions of mothers could have been restored by providing HAART to all HIV-infected pregnant women and their infants.

Instead of applying historic advances in HIV prevention and treatment that were being heralded at the international AIDS conferences between 1996 and 1998 to HIV-infected pregnant women in resource poor countries, the pediatric clinical research community invoked an entirely new unvetted interpretation of what was ethical in clinical research by using an economic standard for delivering standard of care— at its worst it was deemed acceptable to withhold treatment and continue the use of a placebos in clinical research studies. The pediatric HIV community, originally a strong defender of the rights of HIV-infected women to receive the best of prevention and treatment, became the only group in the HIV community to withhold standard of care. Pity the HIV infected pregnant women in poor countries who for almost two decades were enrolled in clinical research studies that failed to provide them with the same standard of care that was available to the rest of the world.

By 2012 the International AIDS Society, representing thousands of HIV experts, and the US Public Health Service recommended that all HIV-infected pregnant women be treated with HAART regardless of CD4 count or clinical features. But words and documents don’t translate into action especially when there’s too much to be personally gained from conducting clinical research at a time when research funding for NIH had increased so dramatically. And so, even now in 2014, NIH supported studies, against all recommendations by other organizations, still discontinues potent antiretroviral treatment in HIV infected pregnant women after they deliver their infants.

Curiously, but not surprisingly, some of the countries most affected by the HIV epidemic in Africa were steps ahead of the NIH and even WHO. They had already taken the lead in prevention and treatment, not waiting for WHO and the NIH to catch up. They were recommending providing lifelong treatment with HAART for all HIV-infected pregnant women.

It was a shock therefore to read the most recent revisions of the NIH sponsored study “IMPAACT 1077/Promise” which had enrolled thousands of HIV-infected pregnant women but had not stopped the study to offer all of them lifelong treatment with HAART. Equally surprising, the clinical research investigators had somehow persuaded the ministries of health in the countries who were officially recommending lifelong treatment of women,  to not provide recommended treatment for some of the women enrolled in the research studies. In short, an HIV-infected pregnant women who enrolled in the IMPAACT 1077 study could find herself receiving lesser treatment than recommended by her own country health ministry, and if enrolled in the study, would not be assured of lifelong HAART after the study was completed. It would seem that a proper informed consent would’ve protected women from agreeing to participating in such a study.

But the informed consent that they were given, some 15-17 pages long and listing all the side effects of drugs which even healthcare workers might have difficulty in understanding, did not inform them that could receive inferior treatment that would place their health and that of their infants and sexual partners at risk. Rather the most recent informed consent stated, “The PROMISE [IMPAACT 10077] study has been designed to look for the best ways to prevent the transmission of HIV from a mother to her baby during pregnancy, labor and delivery and breast-feeding and ways to make sure that both the HIV-infected mother and HIV exposed baby stay as healthy as possible from birth and beyond weaning.”

What the mothers enrolling in the study were not told was that the optimal therapy during pregnancy and following pregnancy was already known that they were not going to get it. Additional inaccurate and deceptive language was used in the informed consents which stated, “Stopping the anti-HIV medications after use for prevention of transmission to the baby in the women who would not be on the medications for their own health is often done in the US and other countries.” (In the US and Europe it would’ve been considered malpractice to stop treatment of an HIV-infected woman for purposes of research.)

Informed consents also excluded mentioning other risks of stopping treatment treatment such as continued susceptibility to opportunistic infection, acceleration of HIV disease progression, increased clinic visits and hospital stays. The informed consent also weakened the conclusions of a major international research study showing that HAART dramatically reduced the potential for HIV transmission instead stating instead, “…can make it less likely…” How could so called informed consents, required by US law to conduct annual reviews have been approved by multiple academic Institutional Review Boards (IRBs)? There are only a few possibilities—either they were uninformed about HIV prevention and treatment advances, indifferent to the impact of giving vulnerable HIV-infected pregnant women inferior treatment, possessed conflicts of interest favoring clinical research at their institutions or had not conducted the annual review of clinical research studies sponsored by the NIH as required by US law. Whether one or more of these reasons existed the risk to HIV-infected pregnant women and their infants was unacceptable.

1. IMPAACT 1077HS. HAART standard version of the promise study. 2012. http://www.nichd.nih.gov/research/supported/Pages/impaact.aspx

2. Cohen J. Breakthrough of the year. HIV treatment as prevention. Science 2011; 334(6063): 1628.