Evidence of Immune Reconstitution in Antiretroviral Drug-Experienced Patients with Advanced HIV Disease

Abstract

Highly active antiretroviral therapy (HAART) of HIV disease is associated with effective virologic control, immune reconstitution, and clinical improvements. This study addresses the potential for improvements in lymphocyte phenotype and virologic responses of HIV-infected persons with extensive experience with dual nucleoside reverse transcriptase (NRTI) treatment and advanced HIV disease after a change to a potent antiretroviral therapy (NRTI + protease inhibitor). The majority of participants achieved virologic success. There was a median rise in CD4+ lymphocytes of 99 cells/mm(3) by 48 weeks, because of an increase in memory CD4+ cells at 4 and 16 weeks, followed by a later increase in naive CD4+ cells between weeks 16 and 48. The proportion of activated, DR+ CD38+ CD8+ lymphocytes decreased during the 48 weeks of follow-up. The immunologic findings (increased memory and naive T cells and reduced activation levels) were significantly improved in participants with persistent suppression of viral replication over the 48 weeks of the study. Baseline HIV RNA copy number was lower (median, 14,784 copies/ml) in persons who responded virologically than in those not suppressing viral replication (median, 49,454 copies/ml). CD4+ cell counts above the median (125/mm(3)) at time 0 for the participants, was the only baseline immunologic marker significantly associated with viral suppression at week 48. Participants older than 40 years of age demonstrated less immunologic recovery. The results of the study show that patients with extensive experience with NRTIs respond both virologically and immunologically during the first 48 weeks of therapy with a potent antiretroviral regimen.

Leprosy and HIV Coinfection: A Clinical, Pathological, Immunological, and Therapeutic Study of a Cohort from a Brazilian Referral Center for Infectious Diseases

“…Although an early increase in both CD4 + T cells and memory CD4 + T lymphocytes can be noticed after 4 weeks of HAART, it has been shown to persist for 48 weeks [25]. Therefore, the timeline for IRIS occurrence might be longer than was previously proposed [38].…”

“…Our group previously observed that Mycobacterium leprae-infected and HIV-infected patients who manifest borderline lepromatous leprosy and AIDS might shift to borderline tuberculoid disease after implementation of highly active antiretroviral therapy (HAART) and leprosy multidrug therapy, which suggests that, in some patients, granuloma formation might be altered by a HAART-induced increase in the CD4 + T cell count [23,24]. Another consequence of HAART-induced CD4 + T cell count improvement [25] is an apparent clinical deterioration that has been noted in a subgroup of patients, an immunopathological and inflammatory phenomenon known as immune reconstitution inflammatory syndrome (IRIS) [26]. Tuberculosis, Mycobacterium avium complex infection, cryptococcosis [27], cutaneous leishmaniasis [27,28], and other infectious and noninfectious diseases have been associated with IRIS [27].…”

Long-Term Follow-Up of HIV-Infected Individuals Who Have Significant Increases in CD4+ Cell Counts during Antiretroviral Therapy

“…Decreases in activated CD4 and CD8 surface markers occur simultaneously and seem to be correlated with viral suppression [36]. Discordant responses among patients, such as increases in the CD4 + cell count despite the lack of suppression of viral replication, usually are differentiated by higher numbers of memory CD4 + cells and activated (CD38 + ) CD8 cells, as well as by a lower percentage of IL-2-producing CD4 + cells [37].…”

Gastrointestinal complications of HIV infection: changing priorities in the HAART era

“…Among responders, the level of HIV RNA in plasma (viral load) falls by several orders of magnitude within the first 2–4 weeks of therapy, becoming “undetectable” (<50 copies HIV RNA/ml) within 16–24 weeks (fig 1). The CD4 count may return to normal with maximal virological suppression if HAART is given for a prolonged period of time,6 and immunological activity may largely be restored 7. Over the last decade, newer agents continue to be developed as additional viral and cellular host targets are identified, with 25 agents currently approved and on the market, with >10 more promising drugs in development (table 1).…”