By Liz Highleyman

About 60% of a cohort of Belgian patients who previously had advanced HIV disease and started HAART in the mid-1990s are thriving, many with undetectable viral load and near-normal CD4 cell counts, according to a study presented at the recent 11th European AIDS Conference (EACS) in Madrid Spain (October 24-27, 2007).

The PICASSO cohort consisted of 395 Belgian patients who had advanced immune deficiency with a CD4 cell count below 100 cells/mm3 (median 26 cells/mm3) when they started triple-combination antiretroviral therapy in 1996, when the first protease inhibitors (PIs) became available. Most had an AIDS diagnosis at study entry or during follow-up. Almost all had used nucleoside reverse transcriptase inhibitor (NRTI) monotherapy or dual therapy before starting HAART.

Most study participants (72%) were men, the average age at study entry was about 39 years, about three-quarters were white, most of the remainder were of African descent, and the most common routes of HIV transmission were heterosexual sex (46%), male-male sex (40%), and injection drug use (7%).

Results

• 16% of patients were lost to follow-up over 10 years.

• At the end of follow-up, about 70% remained on PI-based regimens, about 20% were on NNRTI-based regimens, and about 10% were taking enfuvirtide (Fuzeon; T-20).

• After 10 years on HAART, 61% of the patients remaining in the study were still alive.

• The death rate was highest during the first year on HAART (13 deaths), then fell and remained stable thereafter (2-5 deaths per 100 person-years).

• Overall, about half of the deaths were due to HIV/AIDS-related causes (mostly opportunistic infections or wasting syndrome), 33% were not HIV-related, and 15% were of unknown cause.

• Deaths related to HIV/AIDS fell from about 70% during the first year on HAART to about 40% thereafter.

• 16% of non-HIV-related deaths were due to cancer and 9% were due to chronic hepatitis B or C.

• 70% of patients still being followed had an undetectable HIV viral load (< 50 copies/mL).

• 55% had a CD4 cell count above 500 cells/mm3 (median 364 cells/mm3).

• People with undetectable viral load were more likely to have a higher CD4 cell count.

While these results are highly promising for people on long-term antiretroviral therapy, another study at the conference indicated that CD4 cell increases may be limited for people who start treatment with advanced immune suppression.

As previously reported, researchers with the UK Collaborative HIV Cohort (CHIC) Study in August published results of an analysis of CD4 cell count changes among untreated people with HIV. At EACS, the researchers described CD4 count changes among people treated with HAART.

The CHIC cohort included more than 17,000 HIV positive British participants, of whom more than 4500 started antiretroviral therapy between 1998 and 2005; 68% maintained an undetectable viral load through the end of 2005. The present analysis included about 630 people followed for at least 5 years.

Results

• Overall, CD4 cell gains were higher among patients with lower pre-treatment levels:

•	Baseline CD4 count < 25 cells/mm3: gain of 389 cells/mm3;
•	Baseline CD4 count 50-100 cells/mm3: gain of 309 cells/mm3;
•	Baseline CD4 count 200-350 cells/mm3: gain of 289 cells/mm3;
•	Baseline CD4 count 350-500 cells/mm3: gain of 281 cells/mm3;
•	Baseline CD4 count > 500 cells/mm3: gain of 160 cells/mm3;

• However, other than for those with the lowest and highest pre-treatment levels, CD4 cell gains were similar, around 300 cells/mm3.

• CD4 cell increases were greatest soon after starting antiretroviral therapy (nearly 200 cells/mm3 during the first year), but then declined (about 15 cells/mm3 during the year 5).

• Patients who started treatment with lower CD4 cell levels still had lower counts at the end of follow-up compared to those who started with higher pre-treatment counts.

Based on these findings, the researchers concluded that CD4 cell increases are similar for most patients (other than those starting with the lowest or highest counts). These results add further weight to the recommendation that treatment should be started early, before extensive CD4 cell loss, in order to achieve near-normal CD4 cell counts on HAART.

11/06/07

References

A Libois, S De Wit, B Poll B, and others. Ten year follow-up of patients starting protease inhibitor (PI) with CD4 below 100/ul: the PICASSO cohort. 11th European AIDS Conference (EACS). Madrid, Spain. October 24-27, 2007. Abstract PS1/1.

R Hughes, C Sabin, J Sterne, and others. Long-term Trends in CD4 Count in Patients Starting HAART: UK-CHIC Study. 11th EACS. Abstract P18.4/04