Anti-HIV antibody development up to 1 year after antiretroviral therapy initiation in acute HIV infection
Julie L. Mitchell, … , Lydie Trautmann, on behalf of the RV254 and RV304 Study Groups
Julie L. Mitchell, … , Lydie Trautmann, on behalf of the RV254 and RV304 Study Groups
Published November 11, 2021
Citation Information: J Clin Invest. 2022;132(1):e150937. https://doi.org/10.1172/JCI150937.
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Research Article AIDS/HIV Immunology

Anti-HIV antibody development up to 1 year after antiretroviral therapy initiation in acute HIV infection

Abstract

Early initiation of antiretroviral therapy (ART) in acute HIV infection (AHI) is effective at limiting seeding of the HIV viral reservoir, but little is known about how the resultant decreased antigen load affects long-term Ab development after ART. We report here that Env-specific plasma antibody (Ab) levels and Ab-dependent cellular cytotoxicity (ADCC) increased during the first 24 weeks of ART and correlated with Ab levels persisting after 48 weeks of ART. Participants treated in AHI stage 1 had lower Env-specific Ab levels and ADCC activity on ART than did those treated later. Importantly, participants who initiated ART after peak viremia in AHI developed elevated cross-clade ADCC responses that were detectable 1 year after ART initiation, even though clinically undetectable viremia was reached by 24 weeks. These data suggest that there is more germinal center (GC) activity in the later stages of AHI and that Ab development continues in the absence of detectable viremia during the first year of suppressive ART. The development of therapeutic interventions that can enhance earlier development of GCs in AHI and Abs after ART initiation could provide important protection against the viral reservoir that is seeded in individuals treated early in the disease.

Authors

Julie L. Mitchell, Justin Pollara, Kenneth Dietze, R. Whitney Edwards, Junsuke Nohara, Kombo F. N’guessan, Michelle Zemil, Supranee Buranapraditkun, Hiroshi Takata, Yifan Li, Roshell Muir, Eugene Kroon, Suteeraporn Pinyakorn, Shalini Jha, Sopark Manasnayakorn, Suthat Chottanapund, Pattarawat Thantiworasit, Peeriya Prueksakaew, Nisakorn Ratnaratorn, Bessara Nuntapinit, Lawrence Fox, Sodsai Tovanabutra, Dominic Paquin-Proulx, Lindsay Wieczorek, Victoria R. Polonis, Frank Maldarelli, Elias K. Haddad, Praphan Phanuphak, Carlo P. Sacdalan, Morgane Rolland, Nittaya Phanuphak, Jintanat Ananworanich, Sandhya Vasan, Guido Ferrari, Lydie Trautmann, on behalf of the RV254 and RV304 Study Groups

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Figure 2

Continued Ab development after ART initiation in participants treated in S2 or later of AHI.

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Continued Ab development after ART initiation in participants treated in...
(A) Time required for the VL to first reach undetectable levels (VL 20 copies/mL) after ART initiation for participants who initiated ART at different stages of AHI. (B) The log VL AUC was calculated for each participant. Plasma levels of gp41-specific (C) and gp120-specific (D) Abs were measured by ELISA after 24 (W24) and 48 (W48) weeks of ART. (E) Correlations between Ab levels at week 24 and week 48 are shown for gp41-specific and gp120-specific Abs. (F) Proportion of participants who had measurable ADCC responses (responders) at each visit using target cells infected with CRF01_AE virus. (G) ADCC function of plasma Abs after 24 and 48 weeks of ART in participants who initiated treatment during AHI or CHI. (H) Correlation between ADCC Ab titers at week 24 and week 48. Differences in the proportion of participants responding at each visit were calculated using a χ2 test and the Marascuilo procedure (dagger symbol indicates significant differences in proportions). Differences in VLs, AUC, or Ab levels between AHI stages were measured by a Kruskal-Wallis test with Dunn’s multiple-comparison test (black asterisks). Differences in Ab levels between visits were measured by a Wilcoxon matched-pairs, signed-rank test (light gray asterisks). For week 0 and week 24: n = 12 for S1; n = 17 for S2; n = 14 for S3; and n = 9 for S4/5. For week 48: n = 11 for S1; n = 15 for S2; n = 13 for S3; and n = 9 for S4/5. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001