Concurrent administration of IFNα14 and cART in TKO-BLT mice enhances suppression of HIV-1 viremia but does not eliminate the latent reservoir

• Published in: Scientific reports 2019-12, Vol.9 (1), p.18089-6, Article 18089
• Main Authors: Sutter, Kathrin, Lavender, Kerry J., Messer, Ronald J., Widera, Marek, Williams, Katie, Race, Brent, Hasenkrug, Kim J., Dittmer, Ulf
• Format: Article
• Language: English
• Subjects: 631/326/596/2556; 631/326/596/2564; 64; 64/110; 64/60; Animals; Anti-Retroviral Agents - administration & dosage; Anti-Retroviral Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antiviral Agents - administration & dosage; Antiviral Agents - therapeutic use; CD4 antigen; Deoxyribonucleic acid; DNA; Drug Therapy, Combination; Female; HIV; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Immune system; Immunodeficiency; Interferon-alpha - administration & dosage; Interferon-alpha - therapeutic use; Lymphocytes T; Male; Mice; Mice, Inbred C57BL; multidisciplinary; RAG2 protein; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Spleen; Viral Load - drug effects; Viremia; Viremia - drug therapy; Viremia - virology; α-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-54650-9

Combination antiretroviral therapy (cART) prevents HIV-1 replication but does not eliminate the latent reservoir and cure the infection. Type I interferons (IFN) mediate antiviral effects through different mechanisms than cART. We previously showed that IFNα14 is the most potent IFNα subtype against HIV-1 and that it can significantly reduce the HIV-1 proviral reservoir. This study sought to determine whether combining cART with IFNα14 therapy would produce greater reductions in HIV-1 viral and proviral loads than ART alone. Immunodeficient Rag2 −/− γ c −/− CD47 −/− C57BL/6 mice were humanized by the BLT method, infected with HIV-1 JR-CSF and the in vivo efficacy of cART was compared with combined cART/IFNα14 therapy. Infection was allowed to establish for 6 weeks prior to 4 weeks of treatment with oral cART either with or without IFNα14. Plasma viral RNA and splenic CD4 + T cell viral DNA levels were measured immediately after treatment and after 2 weeks of therapy interruption. Augmentation of cART with IFNα14 resulted in significantly enhanced suppression of HIV-1 plasma viremia. However, no significant reduction in total viral DNA was detectable. Furthermore, virus rebounded after treatment interruption to similar levels in both groups. Thus, augmentation of cART with IFNα14 resulted in a more pronounced reduction of HIV viremia levels over cART alone, but the effect was not potent enough to be detected at the viral DNA level or to prevent virus rebound following therapy interruption in immune system-humanized mice.