CD4 Cell Count Improves with HAART-especially Protease Inhibitors Even if Viral Load Is Not Fully Suppressed

By Liz Highleyman

A majority of people currently being treated with combination antiretroviral therapy (ART) live in resource-limited settings, where it is common for patients to remain on virologically failing regimens, typically containing a non-nucleoside reverse transcriptase inhibitor (NNRTI).

As reported at the recent 9th International Congress on Drug Therapy in HIV Infection (HIV9) in Glasgow, Scotland, Andrew Phillips, Amanda Mocroft, and colleagues with the EuroSIDA study aimed to identify the viral load level at which CD4 cells begin to decrease significantly in patients on ART, as well as factors associated with changes in CD4 count.

The analysis included 7231 patients contributing a total of 58,929 CD4 slopes (median 6 per person). CD4 slopes were calculated from 3 consecutive CD4 cell measurements performed while viral load was stable (defined as < 0.5 log10 copies/mL difference between the highest and lowest viral loads). Slopes were calculated over a median 6.6 months.

Results

• Patients who maintained HIV RNA < 500 copies/mL experienced a CD4 count gain of nearly 50 cells/mm3.

• Those with 500-999 copies/mL experienced a consistent CD4 cell decrease, ending up almost 75 cells/mm3 below the first measurement.

• Among those with HIV RNA of 1000 copies/mL or more, the CD4 decline was greater, ending with a loss of more than 100 cells/mm3.

• Patients on combination ART had more favorable -- that is, more positive or less negative -- mean CD4 slopes than those off therapy at any viral load level.

• Treatment-naive patients, however, had more favorable CD4 slopes than patients who had previously started ART but were undergoing treatment interruption.

• Among treated patients, after adjusting for confounding factors, regimens containing a single protease inhibitor (PI) (mean CD4 slope 43 cells/mm3) or a ritonavir-boosted PI (47 cells/mm3) were associated with more positive CD4 slopes than NNRTI-based regimens (31 cells/mm3) or triple-nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) regimens (30.2 cells/mm3) (P < 0.0001).

"The results from our study would suggest that some treatment with combination ART is better than none, but also that better CD4 count increases are obtained by using a PI or ritonavir-boosted PI-based regimen than by using an NNRTI-based regimen," the investigators concluded.

Based on these findings, they recommended that, "Patients with stable viremia unable to fully suppress HIV replication should continue therapy and consideration should be given to the use of a PI-based regimen."

Royal Free and University College Medical School, London, UK; University Hospital, Zurich, Switzerland; Medizinische Poliklinik, Munich, Germany; Hospital Saint-Antoine, Paris, France; Medical University, Bialystok, Poland; Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam, Netherlands; Copenhagen HIV Programme, Panum Institute, Copenhagen, Denmark; Copenhagen HIV Programme, Panum Institute and Centre for Viral Disease KMA, Rigshospitale, Copenhagen, Denmark.

12/9/08

Reference
AN Phillips, B Ledergerber, JR Bonger, and others. Rate of change in CD4 counts in patients with stable HIV viremia. 9th International Congress on Drug Therapy in HIV Infection. Glasgow, Scotland. November 9-13, 2008. Journal of the International AIDS Society 11(Suppl 1): O17. November 10, 2008.