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Virologic Failure Is Uncommon After Treatment Is Initiated During Acute HIV Infection
Trevor A. Crowell1; Nittaya Phanuphak2; Suteeraporn Pinyakorn1; Donn Colby2; Somporn Tipsuk2; Putthachard Kansomlap2; Naphassanant Laopraynak3; Robert O'Connell4; Merlin L. Robb1; Jintanat Ananworanich5; for the The RV254/SEARCH010 Study Group
1US Military HIV Rsr Prog, Walter Reed Army Inst of Rsr, Silver Spring, MD, USA;2SEARCH, Bangkok, Thailand;3HIV-NAT, Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand;4Armed Forces Rsr Inst of Med Scis, Bangkok, Thailand;5Military HIV Rsr Prog, Bethesda, MD, USA
When initiated during chronic HIV infection, antiretroviral therapy (ART) generally produces a swift decrease in viral load (VL) and suppression within 24 weeks. We investigated viral dynamics and common criteria for treatment success after ART initiation during acute HIV infection (AHI).
Subjects were prospectively enrolled and offered ART during AHI from May 2009-February 2015 in Bangkok, Thailand. Regimens included tenofovir, lamivudine, and efavirenz with or without raltegravir and maraviroc. Subjects were monitored for the following VL endpoints: (1) 1-log reduction by week 2; (2) 2-log reduction by week 4; (3) <1000 copies/mL by week 24; and (4) <200 copies/mL by week 24. Associated factors were explored using the chi-squared test and t-test. The log-rank test was used to evaluate associations with time to VL <200 copies/mL.
From 130,704 samples screened for HIV, 237 Thai subjects were enrolled and initiated ART during AHI. Their median age was 27 years and 95% were male. ART was initiated during Fiebig I in 15%, Fiebig II 29%, Fiebig III 40%, Fiebig IV 11%, and Fiebig V 5%. ART included raltegravir and maraviroc for 84 subjects (35%) and regimens did not differ by Fiebig stage (p=0.382).
Only 16 of 236 (6.8%) subjects with VL data at week 2 did not achieve a 1-log reduction in VL. At 4 weeks, 25 of 234 (10.1%) had not achieved a 2-log reduction in viral load. At 24 weeks, 3 of 230 (1.3%) had not reached VL <1000 copies/mL and 4 (1.7%) had not reached VL <200 copies/mL.
Subjects treated during Fiebig I had lower VL at ART initiation (mean [SD] 4.31 [0.69] log10copies/mL vs. 6.0 [0.88] in all other subjects, p<0.0001) and were the least likely to achieve early reductions in VL (Figure). At baseline, nine (25%) had VL <5000 copies/mL and none had VL <500 copies/mL. All subjects who initiated ART during Fiebig I achieved VL <200 by week 24 and the median time to viral suppression in this group was only 4 (IQR 2-8) weeks compared to a median 8 (IQR 4-12) weeks for all other Fiebig stages (p=0.002). Subjects who received raltegravir and maraviroc had a median time to suppression of 4 (IQR 4-8) weeks compared to a median 8 (IQR 8-12) in subjects who did not (p<0.0001).
Subjects who begin ART during Fiebig I have a low VL and do not demonstrate the same magnitude of early VL decline as is seen when ART is started later. Treatment success can be readily assessed after 24 weeks of ART initiated during AHI. Virologic failure was uncommon in this cohort.