News from the 13th International AIDS Conference, July 9-14, Durban, South Africa
Other U.S. researchers noted that with improved HIV therapies, there will be greater concern over the potential for pain and other quality of life problems in people living with the virus, but that no one has looked at pain in children. PACTG 219 (Pediatric AIDS Clinical Trials Group) found in a survey that children with a CD4 percentage of less than 15% (severely immune suppressed) were almost three times more likely to report pain. (In children, CD4 percentage is more important than T-cell counts.) Overall, 20% (one in five) of the children experienced pain. The research is important because adults are frequently unable to notice pain in children.
A big question: do children born to mothers on HIV drugs get hurt by the medications? Most research shows that they don't. But researchers from the Netherlands reported immune system damage and blood cell malfunctions (such as much less CD4 T-cells) in negative children of positive moms. The report started a storm of controversy in the audience. Among the issues raised was the fact that this was a one-time look at the umbilical cord blood at birth; the researchers are still looking at how fast the children's immune system recovers; and that these may be transient problems (the presenter said they will look at that).
Brazilian researchers found a high level of blood lipid changes (51%) in children and adolescents on anti-HIV drugs (as is found in adults). Those with a longer history of symptomatic disease had a greater risk of lipid problems (more cholesterol or triglycerides, a type of fat). Actual changes in physical appearance was greater in the kids taking a protease inhibitor (five out of 29, compared to one out of 37 using only two nucleoside analogues -- such as Zerit and Epivir). "Protease inhibitors seem to play a significant role in the development of abnormal body fat distribution," the presenter said.
Researchers reported good preliminary results in children, even those who previously took medications (a group that tends to show less benefit), with the newest protease inhibitor, lopinavir (formerly known as ABT-378/r), expected to be approved by the FDA (Food and Drug Administration) soon. After four months, undetectable viral load (less than 400) was seen in 57% of kids who had previously taken a protease inhibitor, 77% of kids who had taken a nucleoside analog, and 79% of kids who had never taken anti-HIV therapy before. The children's starting viral load was not given. The PI-experienced children received Viramune in addition to lopinavir and two nucleoside analogs. A doctor in the audience said that much higher doses of the manufacturer's current protease inhibitor, Norvir, had to be used in infants because the company didn't have enough research to provide adequate pharmacokinetics (how the drug works in the blood) in that population. He cautioned that since very few children here were less than two years old, and only one was less than six months old, the pharmacokinetic data may again end up being different once the drug is on the market. In response to a question, the presenter said the drug is not very palatable (tasty), but can be easily masked and that children, who are now a year into the study, no longer complain about taste.
Mexican researchers found good results with the use of the cancer drug hydroxyurea (Hydrea) in 24 children. They had greater weight gain, growth, increases in T-cells and CD4 percentages, less viral load and less disease after nine months on hydroxyurea (30 mg/kg a day) with Videx and Zerit. The researchers reported good tolerance (plus, no cases of pancreatitis) and noted the lower cost of using hydroxyurea than using one of the potent HIV drugs, an issue raised by other doctors at the conference in terms of adult therapy.
Also comparing well with AZT in short-course therapy was Zerit, Videx and a combination of Zerit/Videx. (Short-courses are studied in an attempt to decrease the cost of the original, longer U.S. trial with AZT that set the standard for preventing transmission.) In this study (also in South Africa), the drugs were given from the 34-36th week of pregnancy, but not during labor. The drugs were also given to the infants for the first six weeks of life. Baby formula was provided. Overall, there was a 3.6% transmission in more than 200 babies. Researchers said all drugs were safe and well-tolerated, and the "d" drugs (Zerit is d4T and Videx is ddI) had as much anti-HIV activity and decreases in transmission as did AZT. There were almost no drug related side effects.
In another study, breastfeeding was found to negate the benefits of AZT. In an analysis of two clinical trials that used short-course AZT in the sub-Saharan countries of Cote d'Ivoire and Burkina-Faso, there was no statistical difference in transmission at 24 months after birth between the women who used AZT (9.4%) and those who were given placebo (fake drug, 8.6%). Researchers noted that women with greater HIV viral load (the amount of virus in their blood) had a greater risk of transmission. It is preferable for HIV positive mothers to breastfeed in developing countries if the families have no access to infant formula or clean water.
In the U.S., four people were put through three cycles of interruption, with four weeks on therapy followed by four weeks off. All started out with undetectable viral loads (considered under 400, in this case) and more than 400 T-cells. After 20 weeks, two of them did not show an increase to above undetectable (called "rebound") after one interruption, but did after the second and third (for a maximum of 14,000 and 25,000 viral load). The other two had a rebound during all three interruptions, with a maximum of 86,000 and 135,000. Viral load came back down with therapy for all four people, but not always to undetectable.
The following News Briefs are not from the International AIDS Conference.