CD4 cell-guided scheduled treatment interruptions in HIV-infected patients with sustained immunologic response to HAART.
OBJECTIVE
To compare continuous HAART with a CD4 cell-driven scheduled treatment interruption (STI) strategy.


METHODS
LOng Term Treatment Interruption study is a randomized, controlled, prospective trial. Patients with CD4 cell counts more than 700 cells/microl were eligible, and the immunologic threshold to resume HAART was 350 cells/microl. The primary end point was the development of an opportunistic disease, death from any cause or the occurrence of diseases, other than opportunistic, requiring hospital admission. Secondary end points were major adverse effects, virologic failures and therapeutic costs.


RESULTS
Three hundred and twenty-nine patients were randomized 1: 1. Total follow-up was 1388 person-years (mean 4.2 years). Patients in the STI group stopped therapy for a total of 241 STI cycles, their mean off-therapy period was 65.3% of the follow-up. The primary end point occurred in 12.1% of patients on STI and in 11.6% of controls [odds ratio 1.05; 95% confidence interval 0.54-2.05]. A higher proportion of patients in the STI arm were diagnosed with pneumonia (P = 0.037), whereas clinical events influencing the cardiovascular risk of patients were significantly (P < 0.0001) more frequent among controls. Eight patients (4.8%) in the STI group and 11 (6.7%) controls developed viral resistance [odds ratio 0.79, 95% confidence interval 0.27-1.81]. The mean daily therapeutic cost was 20.29 euro for controls and dropped to 9.07 euro in the STI arm (P < 0.0001).


CONCLUSIONS
The two strategies may be considered clinically equivalent. CD4 cell-guided STIs seem a possible alternative for chronically infected individuals responding to HAART provided that CD4 cell decrements would be steadily maintained above a safe threshold.
Maggiolo
Franco
F
Division of Infectious Diseases, Unit of Antiviral Therapy, Ospedali Riuniti, Largo Barozzi 1, 24128 Bergamo, Italy. franco31556@hotmail.com
Airoldi
Monica
M
Callegaro
Annapaola
A
Martinelli
Canio
C
Dolara
Alberto
A
Bini
Teresa
T
Gregis
Giampietro
G
Quinzan
Giampaolo
G
Ripamonti
Diego
D
Ravasio
Veronica
V
Suter
Fredy
F
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D004334:Drug Administration Schedule; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
D012367:RNA, Viral