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Role for Short-Term Enfuvirtide to Boost CD4s After Late Diagnosis?
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49th ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy), September 12-15, 2009, San Francisco
Mark Mascolini
Twenty-four weeks of enfuvirtide plus a lopinavir-based regimen boosted CD4 counts significantly more than a lopinavir regimen alone in a small randomized trial that enrolled people with CD4 counts under 50 [1]. The CD4 benefit appeared to persist through 96 weeks, 72 weeks after enfuvirtide stopped, though only half of the study participants had completed that much follow-up.
Stefano Bonora and University of Torino colleagues defined late presenters as those diagnosed with a CD4 count under 200 and very late presenters as those diagnosed with fewer than 50 CD4s. Up to half of all people diagnosed with HIV in Italy meet these definitions, according to Bonora, and they run a higher risk of dying during the first year of therapy than people with higher T-cell tallies.
This study included 22 people starting their first antiretrovirals with a CD4 count under 50. No one had active tuberculosis, cancer (other than Kaposi sarcoma), any potentially irreversible progressive disease, or progressive multifocal leukoencepthalopathy. No one had pretreatment resistance mutations.
The investigators randomized 11 people to lopinavir/ritonavir plus two nucleosides and 11 to the same regimen plus enfuvirtide, which continued until viral load became undetectable or for 24 weeks. The primary endpoint was CD4-cell gain after 24 weeks of treatment.
The groups did not differ significantly in median starting CD4 count (20 with enfuvirtide versus 16 without, P = 0.47), CD4% (3.3% versus 3.1%), CD4-to-CD8 ratio (0.05 versus 0.03), viral load (median 5.8 versus 5.4 log), age (median 39 versus 44 years), or number taking zidovudine (0 versus 2).
Three people in the control group did not complete the study, 2 because they stopped returning for visits and 1 because of a pulmonary tuberculosis diagnosis. One person in the enfuvirtide group stopped returning for visits.
After 8 and 24 weeks, CD4 gain from baseline was significantly higher in the enfuvirtide group. That difference nearly remained significant through week 48, although the CD4 rise plateaued after week 24 in the enfuvirtide group:
· Week 8: +169 with enfuvirtide, +48 without, P = 0.02
· Week 24: +207 with enfuvirtide, +125 without, P = 0.01
· Week 48: +206 with enfuvirtide, +179 without, P = 0.06
Absolute median CD4 count was significantly higher at 24 weeks with enfuvirtide (240 versus 140, P = 0.03), as was CD4% (17% versus 8.4%, P = 0.04), and CD4-to-CD8 ratio (0.28 versus 0.20, P = 0.02). After 48 weeks, median CD4 count was still significantly higher with enfuvirtide (255 versus 190, P = 0.01), as was CD4% (19.2% versus 12.1%, P = 0.02). Among 10 patients monitored for 96 weeks, median CD4 count remained higher with enfuvirtide (348 vs 264), but this difference lacked statistical significance. CD8 count did not change significantly during the study.
Viral load decline was statistically equivalent at day 7. But by day 28 the drop was significantly greater with enfuvirtide (-3.01 versus -2.35 log, P = 0.03). Time to reaching an undetectable viral load did not differ significantly between groups.
The investigators did not report any between-group differences in short-term clinical progression. They call for a larger study to evaluate clinical progression and to conduct more rigorous immunologic analyses of short-term enfuvirtide in people starting therapy with very low CD4 counts.
Reference
1. Bonora S, Calcagno A, Cometto C, et al. A long-term immunological advantage associated with a short-term additional therapy with enfuvirtide in the treatment of HIV very late presenters. 49th ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy). September 12-15, 2009. San Francisco. Abstract H-924.
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