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A Pilot Open-label Phase II Trial of the Safety and Efficacy of a Compact 3-Drug Antiretroviral Treatment Regimen for Subjects with Acute or Recent Primary HIV-1 Infection
Constance A Benson*1, T Campbell1, S MaWhinney1, E Connick1, J Forster1, G Ray1, M Thompson2, A Landay3, R Badaro4, E Netto4, F Judson5, F Pallela6, and R Schooley1
1Univ of Colorado Hlth Sci Ctr, Denver, USA; 2AIDS Res Consortium of Atlanta, GA, USA; 3Rush Univ, Chicago, IL, USA; 4Federal Univ of Bahia, Salvador, Brazil; 5Denver Hlth Med Ctr, CO, USA; and 6Northwestern Univ Feinberg Sch of Med, Chicago, IL, USA
Background: The optimal approach to antiretroviral therapy (ART)
for acute or recent primary HIV-1 infection (PHI)
and its effect on immune function or disease progression are controversial.
Methods: We conducted a phase II, open-label, pilot
study of the safety and efficacy of ART
vs no treatment in patients with acute or recent PHI. Patients elected to start or not start ART (atazanavir [600mg] +
didanosine-EC + stavudine).
Substitution within the nucleoside reverse transcriptase inhibitor (NRTI)
class, at the discretion of the clinician, was allowed. ART
was continued for ≥ 48 to 104 weeks. All patients were followed through week
104. The primary virologic endpoint was the percentage
of treated patients who achieved and maintained HIV-1 RNA < 50 copies/mL at week 48; the primary efficacy endpoint was the percentage
of patients on assigned ART who
achieved and maintained HIV RNA < 50 copies/mL at
week 48 (ITT, M=F).
Results: We enrolled 55 patients: 95% men, 75% white, median age 33 years; 37 patients
elected to start ART (12 acute, 25
recent); 18 elected not to start ART
(3 acute, 15 recent). Median baseline CD4+ for acute treated (Gp IA), acute untreated (Gp
IIA), recent treated (Gp IR), and recent untreated patients
(Gp IIR) were 478, 496, 605, and 826
cells/μL, respectively. Median baseline
HIV-1 RNA was 146,500; 61,634; 59,756, and 4,280 copies/mL, respectively. Genotypic resistance testing was
performed at baseline for 50 patients; mutations conferring ARV
resistance were present in 25% of acute and 5% of recent PHI (p =
0.08, Fisher’s exact). Of those who started ART,
24 of 37 (65%; 95% CI 47.4 to 79.8) met the primary virologic
endpoint at week 48: 8 of 12 acute (67%;
95% CI 34.8 to 90.1) and 16 of 25 recent PHI
(64%; 95% CI 42.5 to 82.1) (p = 1.0;
Fisher’s exact); 21 of 37 (57%; 95% CI 39.4 to 74.0) met the primary efficacy
endpoint: 8 of 12 acute (67%; 95% CI
34.8 to 90.1) and 13 of 25 recent PHI
(52%; 95% CI 31.3 to 72.3) (p = 0.49).
Median CD4+ at week 48 was 619 for Gp IA;
243 Gp IIA; 763 Gp
IR; and 527 Gp
IIR (p = 0.055 for recent treated vs untreated). Median CD4+ at week 48 overall
for treated vs untreated patients was 725 vs 496 (p = 0.018).
One patient (Gp IIA) had a rapid decline in CD4+
requiring ART before week 48.
Treatment-limiting adverse effects were peripheral neuropathy (2 of 37) and hyperbilirubinemia
(5 of 37).
Conclusions: Although there was a trend toward greater pre-ART drug resistance for acute vs
recent PHI, virologic
success was similar in both and comparable to rates in chronic HIV infection. Atazanavir (600 mg) plus 2 NRTI was reasonably well
tolerated in this setting. Patients treated during acute or recent PHI had higher CD4+ at week 48 than
untreated patients.
Keywords: Acute Primary HIV Infection; Recent Primary HIV Infection; Antiretroviral Treatment of PHI
