Very Early Antiretroviral Treatment of HIV-Positive Infants Slows Progression of Disease, Study Says

Administering antiretroviral treatment to very young, HIV-positive infants, especially when treatment starts before age three months, decreases the chance they will progress to the "advanced stage" of the disease by age three years, according to a study published in the May 11 issue of the Journal of the American Medical Association, Reuters Health reports. Dr. David Berk of the Stanford School of Medicine Division of Infectious Diseases and colleagues involved with the California Pediatric HIV Study Group examined the medical records of 205 HIV-positive infants born in Northern California between 1988 and 2001. Of the 205 children -- who were followed through age three -- about 65% received antiretroviral therapy and/or pneumonia prophylaxis, according to Reuters Health. By age three, 81 of the children had progressed to an AIDS diagnosis, and 41 of those children had died, according to Reuters Health (Gale, Reuters Health, 5/10). Untreated children were significantly more likely to progress to an advanced stage of disease, compared with children who received treatment. Overall, about 62% of untreated children studied progressed to an advanced stage of HIV, compared with 28% of treated children (Berk et al., JAMA, 5/11).

Any Treatment Beneficial
After dividing the children into three groups based on their year of birth, the researchers found that none of the HIV-positive children born from 1996 to 2001 who received a daily regimen of at least three antiretroviral drugs died before age three, but about 55% of children born from 1988 to 1991 and 1992 to 1995 -- when combination antiretroviral treatment was not widely used -- died before age three, the San Jose Mercury News reports. Although children who received a three-drug combination experienced slower disease progression, the researchers found that any type of antiretroviral treatment delayed disease onset and increased survival time, according to the Mercury News (Krieger, San Jose Mercury News, 5/11). However, the earlier the infants received antiretroviral treatment -- especially before age three months -- the better their prognosis, the study says. "Because there are potential drawbacks of very early therapy, ... large, prospective clinical trials defining the differences between very early versus delayed institution of therapy are needed," the study says.

Switching Regimens
In another study in the same issue, Susan Brogly of the Center for Biostatistics in AIDS Research at the Harvard School of Public Health and colleagues found that the need to switch pediatric antiretroviral therapy regimens is "far greater" among children who receive regimens without protease inhibitors and among those who begin therapy at advanced disease stages, Reuters Health reports (Reuters Health, 5/10). Brogly and colleagues studied the trends of antiretroviral treatment for 766 prenatally infected HIV-positive children born in the United States prior to 2004. In 1998 -- two years after protease inhibitors were approved for use in HIV-positive adults -- the government issued pediatric HIV treatment guidelines and highly active antiretroviral therapy including protease inhibitors became more frequently used (Brogly et al., JAMA, 5/11). From 1998 to 2003, about 22% of the HIV-positive children were prescribed a regimen not recommended by pediatric treatment guidelines, according to the study. Of the 753 patients who were treated with any antiretroviral therapy, 606 switched to a second regimen.

Implications
"Once our results were adjusted for age and year of calendar start, we found that older regimens -- those including one and two nucleoside reverse transcriptase inhibitors -- were associated with shorter time to first regimen switch," Brogly said. In addition, the researchers found that children who began treatment when they were severely immunocompromised had a shorter time to regimen switch. Brogly noted that patients who are exposed to more drug classes and specific drugs have a greater risk of developing drug resistance if the regimens are not taken properly, adding, "Switching could also result in a reduction of future treatment options" (Reuters Health, 5/10). In an accompanying editorial, Ram Yogev of Children's Memorial Hospital in Chicago writes, "While it is possible to celebrate the tremendous change in the outcomes of HIV-infected children treated with HAART, it is even more important to continue to prioritize research for the survivors who are now living with a chronic disease" (Yogev, JAMA, 5/11).

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