Combination antiretroviral therapy with raltegravir leads to rapid immunologic reconstitution in treatment-naive patients with chronic HIV infection.
BACKGROUND
In treatment-naive, human immunodeficiency virus (HIV)-infected persons, combination antiretroviral therapy (cART) incorporating raltegravir (RAL) is highly effective for virologic suppression, but characteristics of immunologic recovery have not been described.


METHODS
We performed a 48-week substudy of 15 patients, median age 40 years, within a phase 2 randomized trial of RAL-cART in treatment-naive patients with chronic HIV infection.


RESULTS
Plasma viral load decreased from 5.2 ± 5.3 log10 HIV RNA copies/mL to 2.2 ± 2.4 log10 copies/mL at week 4, reaching <50 copies/mL at week 8 in 13 of 15 patients. Total CD4 T cells increased at week 4, as did central memory CD4 T cells in association with reduction of the immune activation markers HLA-DR and CD38 and immune exhaustion marker PD1 in CD4 and CD8 T cells. Naive CD4 T cells increased at week 24 with appearance of HIV gag-specific interleukin 2, interferon-γ, and CD107a responses in CD4 and CD8 T cells at week 48. Plasma lipopolysaccharide and soluble CD14 decreased, but at week 48 were elevated as compared to healthy volunteers. Altogether, the week 48 immune profile was more favorable in patients taking RAL-cART than in patients treated with non-RAL-cART.


CONCLUSIONS
RAL in first-line treatment regimens results in rapid immune reconstitution with residual low-level microbial translocation.
Department of Microbiology and Immunology.
Suresh
S
Pallikkuth
Margaret A
MA
Fischl
Savita
S
Pahwa
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D011760:Pyrrolidinones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium
HIV; RAL-cART; immune activation; immune exhaustion; immune reconstitution; raltegravir