Young adults with perinatally-acquired HIV from Argentina present differential IPDA-determined HIV reservoir composition and immune phenotype: distinctive strategies needed for HIV cure

LUCIA BAQUERO ; M. ARMANI-TOURRET; A. PERBELIS; S. STOVER; ALEJANDRA URIOSTE; ALICIA SISTO; MARIA JOSE ROLON; JORGE LATTNER; PATRICIA COLL; ALEJANDRO CZERNIKIER; VIRGINIA GONZALEZ POLO; BENENCIO, PAULA; ARIEL OSEGUEDA; YANINA GHIGLIONE; LICHTERFELD, MATHIAS; GABRIELA TURK; NATALIA LAUFER

Conferencia; 12th IAS Conference on HIV Science; 2023

Background:Overall data on young adults with perinatally-acquired HIV (p-HIVYA) is scarce. We have previously reported that p-HIVYA exhibited lower frequencies of PD-1+ T-cells, and higher rates of naïve CD4 T-cells (n-CD4TC) compared to people with HIV (PWH, non-perinatally-acquired). Here, we aimed to perform a deepercharacterization of their immune phenotype and HIV-reservoir composition.Methods:Total, intact and defective proviral (TP, IP and DP) HIV-DNA/1M CD4TC were measured by IPDA in 16 p-HIVYA (20-30-years-old) and 27 PWH: 12 age-pairedcontrols (AC) and 14 time from HIV-diagnosis paired controls (TDC). All participants were Argentinians enrolled between April-2019/December-2022; all onsuppressive ART.Immune phenotype (differentiation, exhaustion, activation, PTK-7 and Ki-67 expression) was evaluated by flow cytometry. Data was analyzed using Kruskal-Wallis, Mann-Whitney, and Spearman-correlation tests.Results:Non-significant lower frequencies of TP- and IP-DNA were observed in p-HIVYA compared to AC and TDC. Lower IP-DNA/CD4TC ratios were observed in p-HIVYAcompared to AC (p=0.007). Furthermore, lower IP-DNA/n-CD4TC ratios were found in p-HIVYA compared to AC (p=0.031) and TDC (p=0.006).In addition to the previously reported increased nCD4TC proportion and decreased PD-1 expression, lower frequencies of effector- and transitional-memoryand terminal-effector CD4TC were found in p-HIVYA compared to AC (p=0.035, p=0.008, p=0.028) and TDC (p=0.001, p=0.018, p=0.004), respectively. Nodifferences were found in Ki-67 and PTK-7 expression.n-CD4TC negatively correlated with set-point viral load logarithm [log10(sVL)] in the cohort as a whole (r=-0.411; p=0.026). Also, log10(sVL) directly andinversely correlated with percentages of DP-DNA and IP-DNA (r=±0.709; p=0.018), respectively, in p-HIVYA but not in AC and TDC.Furthermore, Ki-67+CD4TC inversely correlated with TP-DNA in p-HIVYA (r=-0.809; p=0.021).Conclusions:As expected, p-HIVYA presented greater reservoirs in association with higher sVL. The higher n-CD4TC frequency observed in p-HIVYA cannot be explained byelevated present thymic activity (PTK-7 expression). This disbalance could have been generated early in life and persists during adulthood. Lower IP-DNA/n-CD4TC ratio suggests that n-CD4TC may not serve as a main viral reservoir in p-HIVYA. These findings suggest that acquiring HIV perinatally may implydifferent challenges for reaching a cure.