Nevirapine-based treatment regimen for children previously exposed to single-dose nevirapine shown to be effective

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Switching to nevirapine-based antiretroviral therapy (ART) as a treatment strategy for HIV-infected children previously exposed to single-dose nevirapine has the potential to maintain viral suppression in children, according to the data of the NEVEREST study presented by Dr Ashraf Coovadia at the Fifth IAS Conference on Pathogenesis, Treatment and Prevention in Cape Town.

The study aimed to examine the efficacy of switching from a protease inhibitor-based regimen for children to a non-nucleoside reverse transcriptase inhibitor-based (NNRTI-based) regimen in children previously exposed to single-dose nevirapine (Viramune).

Current guidelines recommend initiating protease inhibitor-based regimens in infants previously exposed to single-dose nevirapine after delivery.

Glossary

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

CD4 cell percentage

The CD4 cell percentage measures the proportion of all white blood cells that are CD4 cells.

statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 

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.

toxicity

Side-effects.

These regimens are more costly and have greater long-term toxicity than NNRTI-based regimens. Given that treatment options for HIV-infected children are limited, investigation into alternative regimens is necessary.

A total of 195 HIV-positive children under two years of age from the Rahima Moosa Mother and Child Hospital in Johannesburg were included in the study. All their mothers had taken nevirapine in an attempt to prevent mother-to-child transmission of HIV. The children were initiated on an antiretroviral regimen consisting of lopinavir/ritonavir in combination with d4T (stavudine, Zerit) and 3TC (lamivudine, Epivir).

After maintaining a viral load below 400 copies for at least three months with this combination, the children were randomised either to continue taking their existing treatment (99 children), or to replace lopinavir/ritonavir with nevirapine (96 children) There were no significant differences in the median ages, viral load or CD4 percentage of the two groups at baseline or at randomisation stage.

To monitor viral suppression of HIV post-randomisation, the children were followed for 52 weeks, during which period they had regular viral load tests with a lower limit of detection of 50 copies/ml.

56.2% of children who replaced lopinavir/ritonavir with nevirapine consistently had a viral load below 50 copies/ml for the 52 weeks compared to 42.4% of children who remained on lopinavir/ritonavir. This difference was statistically significant (p = 0.01).

However, a higher proportion of children treated with lopinavir/ritonavir than those switching to nevirapine maintained a viral load below 1000 copies/ml for the duration of the study (98% vs 80%, p = 0.007), suggesting that the difference in the proportion with viral load below 50 copies/ml may have been driven chiefly by viral load 'blips' resulting from poorer adherence to the protease inhibitor.

Patterns of viral suppression post-randomisation showed that in those children remaining on lopinavir/ritonavir, 42% sustained a viral load of less than 50 copies/ml, 55.5% had viral load between 50 and 1000 copies/ml and 2.1% had a viral load above 1000 copies/ml. This compared to 56%, 23.7% and 20.1% respectively in those who switched to nevirapine.

Factors predicting sustained viral suppression in the children who had switched to nevirapine were found to be having a viral load of less than 50 copies/ml at randomisation and no NNRTI mutations occurring before the initiation of treatment.

It was found that, in the children who had switched to nevirapine, 86.1% of those with a viral load of less than 50 copies/ml at randomisation had a sustained viral load suppression below 1000 copies/ml compared to 63.5% of those with viral load between 50 and 400 copies/ml (p

Of those who had experienced no NNRTI mutations, 88% had sustained viral load suppression of less than 1000 copies/ml compared to only 55.3% in children where mutations had occurred (p=0.007).

The median CD4 percentage at 24 weeks was 30% in the children continuing with lopinavir/ritonavir, compared to 33.2% in those who had switched to nevirapine (p

Two children taking nevirapine died as did two children remaining on lopinavir/ritonavir. Adherence to treatment as determined through medication reconciliation at 36 weeks post-randomisation was found to be 80% in those taking lopinavir/ritonavir and 86% in the children who switched to nevirapine although this difference was not found to be statistically significant.

The results suggest that NNRTI-based regimens for children need to be investigated further, and that a substantial proportion of children who develop resistance as a result of exposure to single-dose nevirapine are able to maintain viral suppression when treated with nevirapine after initial, or induction, treatment with a protease inhibitor.

Further information

A webcast of the presentation by Ashraf Coovadia is available on the IAS 2009 website.