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HIV Antiretroviral Therapy May Not Need to Be Indefinite


July 30, 2012 (Washington, DC) — Two studies presented here at the AIDS 2012: XIX International AIDS Conference indicate that it is possible for "elite controllers" to discontinue antiretroviral therapy (ART) for the treatment of HIV after the virus drops below undetectable viral levels.
Elite controllers are people infected with HIV who do not progress to full-blown AIDS.
The key is early detection and early treatment, Asier Sáez-Cirión, MD, from the Institut Pasteur in Paris, France, told meeting attendees.
Dr. Sáez-Cirión and colleagues conducted the Virological and Immunological Studies in Controllers After Treatment Interruption (VISCONTI) trial of 12 patients with HIV whose infections had been controlled for a median of 76 months (but for as long as 84 months) after interruption of 3 years of treatment with highly active antiretroviral therapy initiated in the first 10 weeks after infection (the VISCONTI patients).
Circulating resting CD25, CD69, HLADR, and CD4+ T cell subsets — naive (TN), central-memory (TCM), transitional-memory (TTM), and effector-memory (TEM) cells — were analyzed. T cell reservoir distribution was compared in the 12 VISCONTI patients and in 8 untreated elite controllers, in whom 90% of HIV RNA levels were undetectable (below 200 copies/mL) for approximately 12 (range, 9 to 14) years.
In the VISCONTI patients, activated CD4+ T cells had significantly higher HIV DNA levels than resting ones (median, 2.7 and 2 log copies/million cells, respectively; P = .005).
HIV DNA was detected in all subsets from all patients, except for 8 of 12 TN cells, which were 10-fold less likely to be infected than all memory subsets (median TN, 1.5; TCM, 2.5; TTM, 2.6; and TEM, 2.4 log copies/million cells;P < .007).
TTM contributed to 56% of this reservoir. The HIV reservoir magnitude and distribution observed in the VISCONTI patients and the elite controllers were the same, except that TCM and TTM equally contributed to the elite controllers' HIV reservoir.
Dr. Sáez-Cirión explained that "in VISCONTI patients, treatment initiated at primary HIV-1 infection leads, after treatment interruption, to a low but inducible durable HIV reservoir, distributed mainly in short-lived memory CD4+ T cells, which mimics the natural distribution observed in elite controllers." In other words, very early treatment could make HIV-infected patients more like elite controllers.
Daniel Kuritzkes, MD, from Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts, presented similar findings from 2 HIV-positive patients who received reduced-intensity conditioning allogeneic stem cell transplantation for hematologic malignancies.
"Functional HIV-1 cure has been described in the setting of myeloablative allogeneic stem cell transplant [alloSCT]...but the effects of alloSCT on viral reservoirs are largely unknown," Dr. Kuritzkes and colleagues note in their abstract. "We studied the longitudinal effects of reduced-intensity conditioning alloSCT on HIV-1 peripheral blood reservoirs" in these patients," they write.
"No HIV-1 DNA was detected 8 to 17 months after alloSCT in peripheral blood mononuclear cells [PBMCs] from the 2 patients, despite the presence of modest levels of total PBMC-associated HIV-1 DNA prior to and 2 to 3 months after SCT (87 to 271 copies/10⁶ PBMCs)," the investigators report.
Both patients remained virologically suppressed on ART, but were either started on prednisone or continued on tacrolimus/sirolimus immunosuppressive therapy for chronic graft-vs-host disease (GVHD) near the time of loss of HIV-1 reservoir detection, Dr. Kuritzkes reported.
HIV DNA became undetectable 8 months after alloSCT, he said. "This may be due to a dilutional effect of donor cell engraftment in the setting of protective ART, the additive effect of cytotoxic therapies, and/or GVHD." Confirmation of these results "by sampling large-volume blood collections and other tissue compartments is warranted," he said.
Dr. Sáez-Cirión and Dr. Kuritzkes have disclosed no relevant financial relationships.
AIDS 2012: XIX International AIDS Conference: Abstracts THAA0103 and THAA0101. Presented July 26, 2012.

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