Hopkins doctor responds to recent media reports on HIV/AIDS clinical trial
A statement from Dr. Jean Anderson, Associate
Professor of Gynecology and Obstetrics at The Johns Hopkins University School of
Medicine and HIV/AIDS Technical Advisor to Jhpiego, regarding media reports questioning
the results of an HIV/AIDS clinical trial in Africa.
Recent media reports have questioned the results of the HIVNET 012 clinical
trial in Uganda showing the effectiveness of a single dose of Nevirapine (NVP) to mother
and newborn in preventing mother-to-child transmission (MTCT) of HIV. Specifically, the
media has reported that the National Institutes of Health failed to manage the clinical
trial appropriately and that there were delays and under-reporting of serious and even
life-threatening adverse effects. As the accusations and allegations get widespread
media coverage, it is important to allow external reviews to proceed (the Institute
of Medicine is currently investigating) and concentrate on established facts regarding
safety and efficacy of NVP, without being swayed by the rather inflammatory language
contained in many of these reports and jumping to unwarranted conclusions.
It is worthwhile to briefly review information about NVP that is
available independent from the Uganda trial:
- Efficacy: There are a number of clinical trials and implementation studies that have
confirmed the efficacy of single-dose NVP, either alone or in combination with short-course AZT,
in significantly reducing the rate of MTCT. These studies have been performed in both
breastfeeding and non-breastfeeding populations and in diverse settings, including other
African countries (Malawi, Kenya, Zambia) as well as non-African settings, such as
Thailand, Ukraine, and India. In a large Thai study, the addition of the single-dose
NVP regimen to a backbone short-course AZT regimen starting at 28 weeks resulted in
MTCT rates of 2% or less. The effectiveness of this regimen was most pronounced when
the mother had more advanced disease, as reflected by low CD4 counts or high viral loads;
these same women would be most likely to transmit infection without any intervention.
- Safety: In six clinical trials in addition to HIVNET 012 there
were no significant clinical or laboratory toxicity noted in over 4,400 women and almost
5,000 infants exposed to single-dose NVP. Serious toxicities were rare and did not differ
in type or in rates between mothers and infants receiving NVP prophylaxis and those
receiving short-course AZT/3TC (SAINT study, South Africa), short-course AZT (Thailand),
or “standard antiretroviral therapy” (various regimens, U.S.). There have been no cases
of liver failure or death attributed to single-dose NVP.
- Resistance: The development of resistance can occur after
administration of single-dose NVP prophylaxis to the mother in 15-40% of cases. This is
not new news—it has been well reported and the potential implications if this occurs
continue to be debated. It is also an issue when NVP is given as part of a combination
antiretroviral regimen that will be stopped after childbirth. This phenomenon is likely
due to the prolonged plasma half-life of NVP (levels documented to persist up to three
weeks or more after a single-dose), which is also probably the reason this intervention
is so effective. It is concerning because of the possibility that future maternal treatment
or response to treatment may be compromised if resistance develops and NVP or other drugs
in the NNRTI class are then less effective. The dilemma is this: Do we withhold a simple,
inexpensive, and effective intervention based on these concerns and wait until expensive
and complex combination regimens (HAART) are available (and health care providers are
adequately trained to use them) and we know how to stop or switch regimen components to
avoid resistance? Or do we take these risks in order to begin protecting babies at risk
for HIV infection now? The decision-making that goes into these judgments may vary by
setting and the resources currently available or likely to be available soon. Research
is currently underway to identify ways of preventing the development of resistance with
use of NVP-containing prophylactic regimens.
There has been a certain amount of inaccurate reporting on this topic. In
several press releases there is mention that the single-dose regimen is not used or
recommended in the U.S., implying a different standard of care. In fact, this regimen
is one of the recommended regimens listed in the U.S. Public Health Service Perinatal
Guidelines when women present in labor and are known or found to be HIV positive and
have not received any antiretroviral therapy prior to labor. Ideally, it is used
infrequently because we hope to identify women in need of intervention earlier in
pregnancy, when they are eligible for longer and more effective regimens. Combination
antiretroviral regimens are recommended in most situations when women present earlier
in pregnancy because they appear to be most effective in reducing MTCT and because
they are widely available in our setting. With regards to the safety issue, many press
reports have confused data relating to safety with chronic or long-term NVP treatment
and single-dose prophylaxis. Chronic treatment with NVP-containing regimens has been
associated with increased risk of liver toxicity and there have been cases of liver
failure and death in individuals on these regimens, including in pregnancy.
The bottom line is that there is ample evidence, apart from the HIVNET
012 study, that use of single-dose NVP prophylaxis is safe and effective. The current
controversy should not imperil programs using this regimen that are in the planning or
implementation phase and that hold the promise of saving many lives.
About Jhpiego
For nearly 40 years, Jhpiego, (pronounced "ja-pie-go"), has empowered front-line health
workers by designing and implementing simple, low-cost, hands-on solutions that
strengthen the delivery of health care services, following the
household-to-hospital continuum of care. We partner with community- to
national-level organizations to build sustainable, local capacity through
advocacy, policy and guidelines development, and quality and performance
improvement approaches.
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