Insights from the “Mississippi baby” and Visconti cohort have shed light on the benefits of early ART after primary HIV infection to limit reservoir size. We describe two cases of pre- and post-treatment control in perinatally HIV-1-infected youth.
Routine virologic and immunologic parameters were monitored since diagnosis. Study investigations included: HIV reservoir assessments (TILDA and qRT-PCR for total and integrated DNA); cell-mediated immune responses (CMI); and HLA typing. CMI were assessed using pooled clade-matched HIV-1 Gag peptide panels in matrix format and IFN-g ELISpot and expressed as spot-forming units (SFU) per 106 PBMC.
Case 1, diagnosed at age 10 years, had an initial viral load (VL) of <50 c/mL, but was positive for HIV DNA (clade C). Subsequently, she had only 2 detectable VLs of 71 and 57 c/mL at age 12 and 17 years respectively, with the remainder below detection. Now 17 years, her CD4 counts have been normal throughout. Case 2 was diagnosed at age 11 months, at which time VL was 128,400 c/mL (clade D); nadir CD4 count was 1170 cells/mL (18%). She received dual ARV therapy until age 3 years without virologic suppression, followed by 3-drug cART which led to suppression. Treatment was interrupted at age 12 years with ongoing suppression (<50 c/mL) for 5 years. Now 18 years, over the past year VLs have been consistently detectable up to 300 c/mL, with intermittent adherence to cART initiated for a single CD4 count of 326 cells/mL.
TILDA in both cases showed low positivity at 1.5 cells/106 CD4+ T cells. Total and integrated HIV DNA measurements were 479 and 102 copies/106 CD4+ T cells for Case 1 and 1076 and 564 for Case 2. Both subjects exhibited strong IFN-g responses (Case 1: 97-7032, Case 2: 0-5103 SFU/106 PBMC) and breadth of antigen recognition (22/22 and 13/14 peptide pools recognized, respectively). These CMI are in the top quartile compared to chronically infected children and adults. Case 1 possessed no HLA genotypes predictive of elite control; Case 2 possessed one HLA-B*81 haplotype.
In contrast to the recently reported French adolescent post-treatment controller who had weak CMI, these youth (one an elite controller, the other a post-treatment controller) demonstrated HIV-specific CMI that are substantively larger and broader than those observed in pediatric or adult patients with viral suppression on cART. These results underscore the potential impact of enhanced CMI in virologic remission in perinatally infected youth.