Glasgow Report # 3

Tuesday, Nov 9

Following are some selected highlights from the Glasgow conference. There is a lot of focus at this meeting on developing immune based therapies to supplement HAART. IL-2, Remune and other approaches are being intensely reseached. Tomorrow, Agouron and Immune Response Corp will discuss Remune + HAART. Today, David Cooper reported a meta-analysis of several IL-2 studies showing enormous increase in CD4 although we knew that. In addition, in his analysis 14 individuals in the group not receiving IL-2 had AIDS events while 9 did in the group receiving IL-2. Two question remains-do these CD4 increases from IL-2 improve the immune system as do CD4 increases from HAART?; and, can administering IL-2 folowing viral load reduction from HAART increase immunity, increase virological improvements from HAART, and can IL-2 reduce or empty the reservoir of integration competent proviral DNA in memory CD4s. Also, can this virus be knocked off after exiting the reservoir. Studies are being planned to answer this question.

HIV Specific CD4 Response in Chronic Infection Reported. Today, Brigette Autran delivered an oral presentation in a Plenary session. She has been conducting leading research for the last two years on immunological reconstitution and HAART. She did the first or one of the first studies on the effect of HAART on the production of naïve CD4 cells. Today, she reported several important pieces of information from her ongoing studies of HAART & immune reconstitution

Switch from PI Regimen to NNRTI Regimen

C Rottman from Germany reported on a study where individuals with <500 copies/ml on a PI regimen were switched to a once-a-day nevirapine+ddI+3TC regimen. Participants had varied treatment background. Overall, 18/24 (75%) had <500 copies/ml at week 32, and 13/24 had <20 copies/ml. Additionally, CD4 increased 48 from baseline. However, if you are undetectable on a PI regimen a 75% success rate of switching is not good enough, in my opinion.But, for those individuals who were NNRTI naïve prior to switching to NVP+DDI+3TC they reported two different results--16/16 had <500 copies/ml and in a second table 90% <500 copies/ml. I'll have to check.

All 3 drugs have long intracellular halflives.

Adding Abacavir As Intensification. C Katlama presented data from her study where Individuals being treated with HAART but who had viral load between 50 and 400 intensified their regimen by adding aacavir. On average, they had a 0.44 log reduction in viral load. About 40% became undetectable. If their baseline viral load was <5000 copies/ml, 62% became undetectable. Individuals who had 3TC resistance appeared to do better than individuals without 3TC resistance. However, individuals with 3 AZT mutatins did not respnd well to abacavir. This study underscores that abacavir can be used in early intensification. If you recently started treatment but have not reached below 50 copies by say for example week 12 you can consider using abacavir with or without an additional drug to intensify your regimen to reach 50 copies/ml.

Switching to a Salvage Therapy When Viral Load is Low. Robert Murphy reported on a salvage therapy after individuals failed amprenavir monotherapy in ACTG study. The patients viral load was low (24,000 copies/ml) when they switched to the salvage regimen. And, they switched fquickly after failure. CD4s were about 340. They received a 4-drug regimen of indinavir+3TC=d4T+nevirapine. Individuals on the other arm of the study who virologicaly faied also received this regimen. After 60 weeks about 80% had <500 copies/ml. This suggests what several researchefforts have also suggested and what I have been recommending in NATAP newsletters as a preventative measure to avoid resistance and failure-monior viral load every 4-6 weeks; if viral rebound is detected, consider switching your PI regimen immediately; because if you catch it quickly you may be able to avoid resistance mutations from causing cross-resistance; staying on a failing regime will result in a buildup of resistance and cross resistance to other PIs. The best chance to respond to a 2nd PI is to catch viral load rebound right away and switch therapy. You may want to check which drugs you may be resistant with by using a resistance test, but they are not always accurate.

Indinavir+Ritonavir. Yesterday, Abbott Labs reported preliminary data on this potent combination. In one study, 7/7 had <40 copies/ml at week 52. In a second study the median VL decrease was 3.6 log in the 17 patients who reached week 24; 100% of patients had <500 copies by week 16 which was sustained at week 24; 80% had <80 copies/ml. The median rise in CD4 cells was 165. Regimen was reported to be well-tolerated. As well, preliminary eidence indicated suppressio of viral load for individuals who failed saquinavir or indinavir. They received only the 2-drug regimen of ritonavir+indinavir.

CSF Viral Load Following Ritonavir+Saquinavir. In a small study of a few individuals, after 48 weeks CSF viral load remained detectable following ritonavir+saquinavir alone. But after adding d4T+3TC CSF viral load was reduced to undetectable.