Research can be hit-or-miss. So it was with the prevention of HIV to newborns. Success with AZT
was followed years later with even more outstanding results with Viramune.
Soon, however, came news that many pregnant women had developed drug resistance to the single-dose
Viramune being innovated for poverty-stricken countries where paying for AZT was out of the question for the
country’s budget. Although it was not clear that this would pose a significant problem for the
women, the drug resistance was worrisome.
As soon as studies found it, all research teams working in this area went immediately back to the
drawing board to figure out ways to resolve the problem. They have had success, although not completely.
But the use of Viramune (generic name nevirapine) for preventing HIV to newborns continued to be
plagued with controversy. This is a tragedy, because the drug is safe and effective—and importantly,
inexpensive or even free—for use in pregnant women and their infants.
In the eye of this storm are doctors like James McIntyre, head of the Perinatal HIV Research Unit
at the University of the Witwatersrand and Chris Hani Baragwanath Hospital, in Johannesburg. Like
U.S. doctors in the early days of the epidemic, healthcare providers like Dr. McIntyre are in the
desperate situation of watching—constantly and without recourse—their patients die.
With all the information—and often, misinformation—swirling around Viramune
treatment in pregnancy, Dr. McIntyre was invited by the organizers of the 12th Annual
Retrovirus Conference (CROI), held in Boston in February, to present a plenary on the use of
the medication in preventing mother-to-child transmission.
A different world
Dr. McIntyre opened his talk with recent reports on the near-elimination of HIV infection
among newborns in the United States. “Unfortunately,” he noted, “the
situation around the world is very different.”
For every child born with HIV in the U.S., there are 3,500 to 4,000 born in other countries.* “
It’s not because we don’t know what to do,” Dr. McIntyre said. “The
messages matter. The reporting makes a difference. The data is found by scientists, but the policy is made by politicians.
“The messages became very confusing. The press reports incorrect toxicity information
in single-dose use nevirapine in pregnant women, confusing it with toxicity from long-term use of the
drug. Serious toxicity is rare with single-dose. So resistance [of the virus to the drug] is the issue.”
Dr. McIntyre summed up his talk by saying, “I think we can move from controversy to consensus.”
History
Back in 1994, the ACTG 076 study (AIDS Clinical Trials Group, a U.S. research network) found a drastic
reduction in mother-to-child transmission (MTCT) with the use of AZT (Retrovir). “We haven’t been
able to translate that yet into developing world situations,” Dr. McIntyre said.
Further studies brought more good news for women and infants (including the effectiveness of short-course AZT,
during the last several weeks of pregnancy). “This [good news] is driven by nevirapine single dose,”
Dr. McIntyre said. In 1999, the HIVNET 012 study found dramatic reductions in MTCT (mother-to-child transmission)
with a single dose of Viramune to the mom and one to the baby.
As a result, Boerhinger Ingelheim, the manufacturer of Viramune, made the drug available free to all impoverished
countries for the use of MTCT prevention, with supportive global action by the Elizabeth Glaser Pediatric AIDS Foundation.
Viramune has now been used by 1.5 million moms and babies.
“So what’s the controversy?” Dr. McIntyre asked. He said there were questions of record
keeping raised. There was also a court challenge necessary to force Viramune treatment for MTCT (by activists in his
country, South Africa). Most recently there was a claim of toxicity not being reported.
Studies presented at this year’s CROI reported finding a higher percent of women in MTCT studies with
HIV resistance to Viramune when using a more sensitive resistance test (real time PCR as opposed to genotype testing).
One of them reported that, “These data emphasize the importance of assessing the clinical implications of
resistant variants.” In other words, how exactly is this drug resistance affecting the woman? Dr. McIntyre—
who also participated in conducting these studies—echoed that sentiment: “I want to emphasize—we
really don’t know the clinical significance of this resistance on these sensitivity tests.”
One preliminary study (16 week results) from Zimbabwe reported at CROI found that women who had used either single-dose Viramune (13 women) or AZT (30 women) during their pregnancy did equally well with follow-up HIV treatment. They received a generic drug combination of AZT, Epivir and Viramune. The average T-cell count of the 43 women went from 128 to 246. Viral load went from an average of 80,000 down to undetectable (less than 500 copies) in 88% of the women (38 of 43). Of the five women with detectable viral load, four had taken short-course AZT and one had taken single-dose Viramune.
Yet another study at CROI reported that women with HIV subtype C (the most common around the world) had a greater incidence of resistance following single-dose Viramune than women with subtypes A or D.
A study presented at CROI on a second pregnancy in which women again used single-dose Viramune found a higher rate of transmission compared to women using the single-dose for the first time. On the other hand, the researchers said that the higher transmission rate is in line with what other studies have found with single-dose Viramune. Dr. McIntyre pointed out that this was the first look at subsequent pregnancy using single-dose Viramune.
Dr. McIntyre referred to his study presented at the World AIDS Conference in Bangkok last summer, which found successful ways to overcome Viramune resistance after single-dose use (adding three days worth of AZT plus Epivir to the mother’s regimen worked best of the strategies tried). Another study presented at this year’s CROI reported the same success.
“Do we need to give the mother nevirapine at all?” Dr. McIntyre asked, echoing another CROI report. “We know that a nevirapine dose to the baby as post-exposure prophylaxis [following birth] works.” A study in Botswana found similar prevention efficacy when the baby was given Viramune but not the mom, compared to when both received the medicine. All mothers and infants were also given AZT.
Dr. McIntyre noted that there are concerns about using Viramune where there’s less than optimal monitoring. He said that data presented at CROI and emerging elsewhere show that women in Africa don’t have a lot of toxicity with Viramune.
The bigger problem, he pointed out, is that less than 3% of pregnant women living with the virus have access to anti-HIV treatment.
And he added a comment bound to make many people unhappy, but at the same time a statement strongly supported by others: “We cannot remove the use of single-dose nevirapine in the absence of any other alternative. But,” he added, “I think we need to explain that to women.”
In his slides, Dr. McIntyre worded his statement with a little more caution and explanation: “The availability of sdNVP should be protected for emergency settings and where no other alternatives are available, to reduce the risk of infection for children, for those women who agree to it.”
For a webcast of Dr. McIntyre’s presentation, including his slides, visit www.retroconference.org.
Editor’s note: It is heart-wrenching to advocates of people with HIV—including healthcare providers—to see mothers without treatment and at the same time, to ask for medications for their children. But it is just as heart-wrenching for doctors and nurses to not be able to give treatment to women and then, because of political ignorance, stubbornness or out-and-out ill-will, also not be able to give an easy, safe, effective and inexpensive treatment to keep infants from getting infected. That is a tragedy on top of a tragedy.—EV
*Approximately 200 children a year have been born with HIV in the United States for the past several years.
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