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; MARIE ARMANI-TOURRET; AILÉN PERBELIS; SOFIA STOVER; ALEJANDRA URIOSTE; ALICIA SISTO; MARIA JOSE ROLÓN; JORGE LATTNER; PATRICIA COLL; ALEJANDRO CZERNIKIER; VIRGINIA GONZÁLEZ POLO; PAULA BENENCIO; ARIEL OSEGUEDA; YANINA GHIGLIONE; MATHIAS LICHTERFELD; GABRIELA TURK; NATALIA LAUFER

Conferencia; 12th IAS Conference on HIV Science; 2023

International AIDS Society

Background: Overall data on young adults with perinatally-acquired HIV (p-HIVYA) is scarce. We have previouslyreported that p-HIVYA exhibited lower frequencies of PD1+ T-cells, and higher rates of naïve CD4 T-cells (n-CD4TC)compared to people with HIV (PWH, non-perinatallyacquired). Here, we aimed to perform a deeper characterization of their immune phenotype and HIV-reservoircomposition.Methods: Total, intact and defective proviral (TP, IP andDP) HIV-DNA/1M CD4TC were measured by IPDA in 16 pHIVYA (20-30-years-old) and 27 PWH: 12 age-paired controls (AC) and 14 time from HIV-diagnosis paired controls(TDC). All participants were Argentinians enrolled between April-2019/December-2022; all on suppressive ART.Immune phenotype (differentiation, exhaustion, activation, PTK-7 and Ki-67 expression) was evaluated by flow cytometry. Data was analyzed using Kruskal-Wallis, MannWhitney, and Spearman-correlation tests.Results: Non-significant lower frequencies of TP- and IPDNA 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/nCD4TC ratios were found in p-HIVYA compared to AC(p=0.031) and TDC (p=0.006).In addition to the previously reported increased nCD4TCproportion and decreased PD-1 expression, lower frequencies of effector- and transitional-memory and terminal-effector CD4TC were found in p-HIVYA compared toAC (p=0.035, p=0.008, p=0.028) and TDC (p=0.001, p=0.018,p=0.004), respectively. No differences were found in Ki-67and PTK-7 expression.n-CD4TC negatively correlated with set-point viral loadlogarithm [log10(sVL)] in the cohort as a whole (r=-0.411;p=0.026). Also, log10(sVL) directly and inversely 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 TPDNA 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-CD4TCfrequency observed in p-HIVYA cannot be explained by elevated present thymic activity (PTK-7 expression).This disbalance could have been generated early in lifeand persists during adulthood. Lower IP-DNA/n-CD4TCratio suggests that n-CD4TC may not serve as a main viral reservoir in p-HIVYA.These findings suggest that acquiring HIV perinatallymay imply different challenges for reaching a cure