The following are highlights from the 1st International AIDS Society Conference on HIV Pathogenesis and Treatment held in Buenos Aires, Argentina during July 2001.
Structured Intermittent Therapy
More data were presented from the National Institutes of Health structured intermittent therapy study. Early data were reported in PI Perspective #31
. Ten people were started on seven days of anti-HIV therapies [d4T+3TC+indinavir (Crixivan) + low dose ritonavir (Norvir)] followed by seven days off. The seven-day cycle was chosen because in previous studies, including people who received optimal anti-HIV therapy, it generally took at least seven days before viral loads climbed back up to detectable levels (over 500 copies/ml HIV RNA) after a therapy interruption. All ten people who participated in this study had taken and responded well to therapy before. As a result, at the start of the study, they had an average CD4+ cell count of about 800. Five volunteers have been in the study for more than six months and an additional three for more than a year. All have undetectable viral loads (below 500 copies/ml) although some have had intermittent blips. An interesting observation was that people who stopped therapy for ten days or longer were more likely to have a blip in viral load. Everyone experienced a significant decrease in triglyceride and cholesterol levels, commonly increased due to the protease inhibitors, especially ritonavir. Further, there have been no indications of resistance developing to any anti-HIV drugs nor are there signs that HIV is replenishing the sites where it likes to hide, such as the lymph nodes.
Study results were presented for tipranavir, a new protease inhibitor being developed by Boehringer Ingelheim. Considerable interest in this drug is driven by data suggesting that it remains active against HIV resistant to most other protease inhibitors. One study compared 1,200mg tipranavir taken twice a day to either 300mg or 1,200mg tipranavir together with 200mg ritonavir taken twice daily. This was only a 14-day study and none of the 31 volunteers had taken anti-HIV therapy before. At study end, there was an average viral load reduction of about 1.5 log (32-fold) among the two groups on tipranavir with ritonavir and about 0.7 log (5-fold) reduction among those taking tipranavir alone. Side effects included diarrhea in all three groups and nausea among those on the high dose tipranavir/ritonavir combination.
A second study involved 41 people who had previously taken multiple regimens that included protease inhibitors but not non-nucleoside reverse transcriptase inhibitors (NNTRIs). At the beginning, participants took twice daily regimens of either 1,200mg tipranavir + 100mg ritonavir or 2,400mg tipranavir + 200mg ritonavir. They also received the NNRTI efavirenz (Sustiva) and one new nucleoside reverse transcriptase inhibitor (NARTI). During the study a new formula of tipranavir was developed and people on the 1,200mg and 2,400mg doses were changed to 500mg and 1,000mg of the new formula respectively. The dosing schedule and dose of ritonavir was not changed. After 48 weeks, 79% of those on the lower dose of tipranavir had viral loads below 400 copies/mL and 68% were below 50 copies. Of those on the higher dose, 50% had less 400 copies/ml and 41% had less than 50 copies. In other words, those receiving the lower dose combination had more pronounced viral load reductions -- a strange outcome. Some researchers speculate this may be due to poorer adherence on the higher dose regimen. Another possible explanation is that the new formulation may not be as stable or effective as hoped. The most common side effects included diarrhea, nausea, headache, dizziness, fatigue and abnormal dreams.
Back to the Project Inform Perspective August 2001 contents page.