Not surprisingly, people on nelfinavir were more likely to develop diarrhea, a well-known side effect of the drug. Those taking atazanavir were more likely to have headaches, abdominal pain and increases in bilirubin levels. People using the higher dose of atazanavir were more likely to stop taking it due to side effects.
There was, on average, very little change in triglyceride or cholesterol levels among the people taking atazanavir while those on nelfinavir had significant increases in these lab markers. Changes in these markers have sometimes been associated with changes in body shape, called lipodystrophy. For more information on lipodystrophy, call Project Inform's Hotline.
|Results After 48 Weeks|
After 48 weeks, 74% of the people who stayed on indinavir had viral load below 500 compared to only 58% of those who switched to indinavir/ritonavir. This difference is almost entirely due to an increase in side effects among those on indinavir/ritonavir. Over twice as many people had to stop and/or switch therapy because of side effects compared to those on the three times daily indinavir regimen. Most side effects included gastrointestinal intolerance, kidney stones, blood in the urine (hematuria) and elevations in lipid levels (lab markers for triglycerides and cholesterol).
Fifty people participated and all had a marked reduction in fat tissue in the cheeks (sunken cheeks) as measured by ultrasonography (ultrasound that produces an image). At the time of the report, four people had received three injections, 29 had four injections and 17 had five. All dramatically improved, with most having "normalized" cheeks. Some experienced some swelling at the injection site.
After 24 weeks, there were no real differences in anti-HIV activity among the three groups, with 49-59% of the people experiencing viral load suppression to under 400 copies. However, there were major differences in changes in triglyceride and cholesterol levels among them. People on the nelfinavir combinations saw their cholesterol levels increase substantially compared to those on abacavir who only had a slight increase. However, only people taking d4T/3TC/nelfinavir had substantial increases in triglyceride levels while the other two groups only had minor increases. Cholesterol and triglyceride increases have been associated with lipodystrophy in some people.
Overall there were no major changes in laboratory markers for diabetes, include fasting glucose and fasting insulin levels. There was, however, a decrease in insulin sensitivity after 48 weeks, but not before. People experienced a progressive increase in markers of fat processing, triglyceride levels and cholesterol levels. The good news is that HDL (good) cholesterol increased as well as LDL (bad) cholesterol resulting in no change in the overall ratio of HDL/LDL.
Additionally, participants saw an increase in weight, trunk fat and limb fat resulting in an overall increase in total body fat. There was also a trend towards an increase in lean tissue. One interesting observation is that insulin resistance developed after weight gain. This can potentially help in understanding the course of lipodystrophies.
The dose of d4T XR used was 100mg once a day for people weighing over 60kg (about 130 pounds) and 75mg once a day for those weighing less than 60kg. d4T XR results in lower peak and higher trough concentrations of the drug compared to regular d4T. Peak concentration refers to the highest amount of drug in the blood soon after taking a dose. Trough concentration refers to the lowest amount of drug in the blood after taking a dose.
Higher peak concentrations are sometimes associated with a higher risk of side effects. Lower trough concentrations are associated with developing anti-HIV drug resistance. It's assumed that lower peak concentrations of a drug will decrease side effects and higher troughs will decrease the risk of developing resistance.
At the end of 48 weeks, there was essentially no difference in response between the two groups, with about 50% of the participants having viral loads below 50 copies and an increase in CD4+ cell counts of about 200. There appeared to be slightly fewer people experiencing peripheral neuropathy (tingling or numbness around the extremities, especially fingers and toes) among those on d4T XR, although they experienced slightly more headaches. A larger study will truly determine the safety profile and effectiveness of d4T XR.
Volunteers were randomly assigned to take tenofovir or placebo in a 2-to-1 fashion, resulting in 368 people on tenofovir and 182 on placebo. At the start the volunteers had, on average, been on anti-HIV therapy for 5.4 years and had viral load of about 2,300 copies and CD4+ cell count of about 427. The average decrease in viral load between the start of the study and week 24 was 0.59 logs among people taking tenofovir. Essentially no changes were noted among those on placebo. Additionally, about 45% and 22% of the participants had viral loads below 400 and 50 copies respectively compared to 13% and 1% respectively of those taking the placebo. Tenofovir was very well tolerated with no significant differences in moderate-to-severe side effects between the two groups.
The study is limited to individuals who need T-20 to put together a viable anti-HIV regimen, must have a viral load over 10,000 copies and have a CD4+ cell count below 50. Physicians are encouraged to give first preference to people who have had an AIDS-defining opportunistic infection within the last 90 days and have a CD4+ cell count below 50 while taking potent anti-HIV therapy. Secondary preference is encouraged for people with CD4+ cell counts below 50 for the last 90 days despite taking potent therapy.