For patients with HIV-1, initiation of antiretroviral therapy (ART) during primary HIV infection (PHI) promoted long-term reduction of HIV reservoir size but did not lower long-term inflammation, according to results published in Clinical Infectious Disease.
Researchers compared the levels of inflammatory markers from patients with HIV treated for >36 months, with sustained HIV-RNA<50 copies/mL, who began ART within one month of PHI (n=77), with those of people treated >12 months after infection (n=73). CD4+ and CD8+ T-cell activation and plasma ultrasensitive HIV-RNA were also measured during the last patient visit.
HIV-RNA levels decreased quicker in patients receiving immediate ART, resulting in a sustained long-term mean difference of -0.6 log10copies/106 peripheral mononuclear blood cells. Immediate treatment also improved CD4+ T-cell counts and CD4:CD8 ratios over the first 4 years, but after the last visit (median 82 months), there were no differences in CD4+ T-cell counts, CD4:CD8 ratio, ultrasensitive HIV-RNA, or inflammation/activation marker levels. No correlation between inflammatory markers and CD4+ or CD8+ T-cell counts, CD4:CD8 ratio, or HIV-DNA levels or ultrasensitive viral load were detected. Sensitivity analyses to rule out the influence of changes to guidelines or antiretroviral drugs all yielded results similar to the main findings.
The lack of association between inflammatory markers and immunovirologic markers suggests that HIV-1 persistence may not be driven by inflammation after long-term ART, and that chronic inflammation is driven by non-HIV factors such as age or smoking.
The results confirm the benefits of early diagnosis and treatment and provide new information on long-term outcomes of patients treated at PHI, leading investigators to emphasize, “the need for complementary strategies to improve long-term outcomes.”
Novelli S, Lécuroux C, Avettand-Fenoel V, et al. Long-term therapeutic impact of the timing of ART in patients diagnosed with primary HIV-1 infection [published online December 2, 2017]. Clin Infect Dis. doi: 10.1093/cid/cix1068