February 4, 2011

Finding The Right Anti-HIV Drugs For Children

(Ivanhoe Newswire) -- It's a well-known fact that children with HIV will need anti-HIV medicines for longer than adults.  A recent study ultimately questions which anti-HIV drugs to start children with and when to switch to a different one if the virus levels begin to increase.  These are questions that must be answered.

Two types of drugs "” protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) "” are just as efficient as part of initial (first-line) treatment for HIV-infected children, as well as delaying the switch to second-line drugs when the viral load begins to increase does not affect long-term viral load outcomes.

These findings will be particularly important for low-income countries where most children with HIV live, and where the accessibility of second-line ART and laboratories to monitor treatment (using viral load) are limited.

The PENPACT-1 study was designed to compare the long-term efficacy of first-line PI-based ART with NNRTI-based ART and moreover to establish when to switch to second-line ART.  266 children from 68 clinics across 13 countries were assigned to begin treatment at random with two NRTIs plus one of four options: a PI and then switch to second-line ART when viral load increased to 1,000 copies per mL (66 children); a PI and then delay switching until viral load reached 30,000 copies per mL (65); an NNRTI and switch at 1,000 copies per mL (68); or an NNRTI and switch at 30,000 copies per mL (67).

The proportion of children with viral load less than 400 copies per mL after 4 years of treatment was similar between PI and NNRTI-based ART.  Furthermore, there was no apparent difference in 4-year viral load between the early (1,000 copies per mL) and delayed (30,000 copies per mL) switch groups, as well as the level of drug resistance to PIs and NNRTIs was similar in these groups.  Nevertheless, over 5 years children starting with NNRTI-based treatment compared to those on PI-based treatment were more likely to develop resistance to NRTIs if switching treatment was deferred until viral load levels reached 30,000 copies per mL.
Regular treatment monitoring using viral load is improbable in averting the development of NNRTI resistance, pointed out the authors, for the reason that it happens exceptionally soon after the viral load rises.  In due course, continuing on an NNRTI-based regimen that is not suppressing viral load adds to the risk that resistance to the NRTI drugs will occur, thus compromising their future use.

Most children responded well, whether starting PI or NNRTI-based first-line ART"”71% were still taking their first-line ART at the end of the study and second-line ART failed in only 7 percent.  The number of children experiencing side effects did not differ between the treatment groups.

"Little difference exists between PI and NNRTI containing initial anti-HIV treatment for children, the authors conclude; both result in good long-term viral load outcomes," the authors conclude. "For children on PI-based treatment, the lack of a difference in the NRTI and PI resistance, suggests that delayed switching might be reasonable in circumstances and settings where future drug options are limited."

"The findings of the PENPACT-1 trial support the recommendation of NNRTI-based regimens as the first-line regimen in low-income countries," which Catherine Sutcliffe and William Moss from the Bloomberg School of Public Health, John Hopkins University, Baltimore, USA, were quoted as saying.

"The findings . . . suggest that delayed detection of virological treatment failure in children who receive NNRTIs, the most common regimen in low-income countries, results in the accumulation of NRTI mutations, potentially jeopardising future treatment options and emphasising the need for programmes that improve access to viral-load monitoring," caution the authors.

SOURCE: The Lancet Infectious Diseases, 31 January 2011