Background:
Initiation of antiretrovirals (ART) during acute HIV infection reduces viral reservoirs with improved long term virologic control; there is limited data on youth. HIV reservoir decay in youth treated during acute HIV infection (A) may be greater than in those treated with non-acute infection (NA). ATN 147 identified A or NA HIV-infected youth (12-24 yr.) assessing HIV plasma RNA PCR, DNA digital drop (dd) PCR and HIV antibody from baseline (BL) to 24 mo.
Methods:
Youth newly diagnosed with HIV infection initiated ART in Los Angeles and New Orleans. Acute infection was defined as Fiebig stage I-V on HIV Western blot (WB) at BL. Fiebig stage VI defined NA infection. Blood was collected over 24 mo. with viral suppression (VS) defined as plasma HIV RNA 20 copies/ml. HIV DNA ddPCR on PBMC and WB were performed at BL, 12, 24 mo. Statistical comparisons at different timepoints/between groups used log-transformed DNA & RNA values in a mixed effect model.
Results:
103 youth enrolled with mean age of 20.8 yr. (range:16-24); 60% identified as black, 25% Latino, 8% white, 7% Asian/Native American; 90% identified as cis-male, 2% cis-female, 5% trans-female, 3% gender nonconforming; 95% reported same gender/bisexual orientation. ART was initiated within 24 hours in 78%, within 1 week in 88%. At BL, 36 (35%) were A and 67 (65%) NA. Median virus load (VL) at BL was 104,650 (A) and 32,334 cps/ml (NA), p < 0.001 & at 4mo. 30 (A) and 20 cps/ml (NA), p =0.815. By 12 & 24 mo. both A and NA had median VL of 20 cps/ml, p=NS. At 4, 12, 24 mo., 50/82 (61%), 52/76 (68%), 41/57 (72%) youth achieved VS. Median ddPCR copies/million PBMCs for youth over time (BL,12,24 mo.) was 844, 192, 127, p < 0.001. For A vs. NA youth, BL,12,24 mo. ddPCR values were 1448 vs. 633, 188 vs. 192, 148 vs. 106, p=0.66. Median dd PCR for VS youth at 12 mo. was 115 vs. 485 in non-VS youth, p < 0.001; at 24 mo. 107 (VS) vs. 202 (non-VS), p < 0.001. Negative/indeterminate (NI) WB occurred in 32% of the cohort at 12 & 35% at 24 mo. NI WB was associated with A status at 12 & 24 mo. (OR 11.5; 95%CI:3.88-34.08). VL suppression at 12 & 24 mo. was not associated with NI WB (OR 2.96; 95% CI 0.91-9.66).
Conclusions:
Early ART induced sustained VS in 68% of youth by 12 mo., significantly reducing HIV DNA and antibody levels. Within 4 mo. of ART, VS was similar in both A and NA youth. HIV DNA decay was similar in A and NA youth with VS. Acutely treated youth were less likely to maintain positive HIV WB.
Median HIV RNA, HIV DNA, and HIV Antibody Responses to Early ART Treatment