Pregnant women with CD4 cell counts over 250 not at greater risk of nevirapine-related toxicity in Kenyan study

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A Kenyan study of nevirapine (Viramune) in pregnant women, most of whom had relatively high CD4 cell counts, has observed that the incidence of liver toxicity and serious allergic reactions is similar to that seen in other nevirapine trials. The study, reported this week at the Twelfth Annual Retrovirus Conference in Boston observed slightly more nevirapine toxicity in women with lower CD4 cell counts.

Women with CD4 counts over 250 cells/mm3 who use nevirapine-based antiretroviral therapy have been shown to be at a greater risk of serious side-effects than women with more advanced disease in studies carried out in North America, Europe and South Africa. This has led to guidelines recommending that nevirapine be avoided in this population, particularly in the developing world.

The Kisumu Breastfeeding Study (KiBS) is an ongoing, single-arm, phase IIB trial to evaluate the safety, tolerance, adherence, and efficacy of nevirapine in combination with AZT (zidovudine, Retrovir) and 3TC (lamivudine, Epivir) in women with HIV. They take the drug combination from week 34 of gestation past childbirth and during breastfeeding to prevent mother to child transmission of HIV. The study is being conducted in Kisumu, Kenya.

Glossary

toxicity

Side-effects.

rash

A rash is an area of irritated or swollen skin, affecting its colour, appearance, or texture. It may be localised in one part of the body or affect all the skin. Rashes are usually caused by inflammation of the skin, which can have many causes, including an allergic reaction to a medicine.

phase II

The second stage in the clinical evaluation of a new drug or intervention, in which preliminary data on effectiveness and additional information about safety is collected among a few hundred people with the disease or condition.

mother-to-child transmission (MTCT)

Transmission of HIV from a mother to her unborn child in the womb or during birth, or to infants via breast milk. Also known as vertical transmission.

efficacy

How well something works (in a research study). See also ‘effectiveness’.

Participants receive frequent clinical and laboratory monitoring for two years after childbirth. Six months after delivery, the women who meet World Health Organization HIV treatment criteria continue on antiretroviral therapy, while the remainder wean their infants and discontinue treatment.

One hundred and fifty-five women were included in the analysis, each providing a median of 13.5 weeks of observation. At baseline, the women's mean CD4 cell count was 458 cells/mm3, with 79% having more than 250 cells/mm3

To date, there have been 13 serious adverse events that led to nevirapine discontinuation, at a rate of 8%. Four of these were grade II, eight were grade III and one was grade IV. Most have resolved completely.

These adverse events occurred at a median of 5.3 weeks after starting nevirapine, putting them close to the time of childbirth.

There were two cases of Stevens Johnson syndrome in patients with CD4 counts of 539 and 302 cells/mm3 but there were no medication-related deaths, in contrast to similar studies in the past.

Contrary to other reports on the use of nevirapine in women, the percentage of serious adverse events in this study was actually higher in those with lower CD4 cell counts, such as rash (3 vs. 5%). However, there were no significant differences in the rate of adverse events, including rash and liver toxicity between women with CD4 cell counts above and below 250 cells/mm3.

In a poster discussion session on Monday, investigator Timothy Thomas warned that the study was not powered to detect a significant difference between these groups. However, the lack of a large difference suggests that the inclusion of more results is unlikely to reveal a dramatic difference between women with high and low CD4 cell counts.

The researchers concluded that their findings underscore the need for close monitoring of women on nevirapine-based highly active antiretroviral therapy, regardless of CD4 cell counts.

References

Thomas T et al. Preliminary findings: Incidence of serious adverse events attributed to nevirapine among women enrolled in an ongoing trial using HAART to prevent mother-to-child HIV transmission. Twelfth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 809, 2005.