Skip to main content

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.

Comments

Post a Comment

Popular posts from this blog

Contact Precautions May Have Unintended Consequences

Contact precautions, including gloves, gowns, and isolated rooms, have helped stem the transmission of hospital pathogens but have also had some negative consequences, according to findings from a new study. Healthcare worker (HCWs) visited patients on contact precautions less frequently than other patients and spent less time with those patients when they did visit, report Daniel J. Morgan, MD, from the University of Maryland School of Medicine and the Veterans Affairs (VA) Maryland Health Care System, Baltimore, and colleagues. Moreover, patients on contact precautions also received fewer outside visitors. "Less contact with HCWs suggests that other unintended consequences of contact precautions still exist," Dr. Morgan and coauthors write. "The resulting decrease in HCW contact may lead to increased adverse events and a lower quality of patient care due to less consistent patient monitoring and poorer adherence to standard adverse event prevention methods (such
Post a Comment
Read more

CareFusion Issues Update on Infant Breathing Product Recall

July 5, 2012 — Medical device maker CareFusion has issued an update reminding healthcare providers of its voluntary recall of its Air Life ™ Infant Breathing Circuit, initiated back in May. The US Food and Drug Administration (FDA) has classified this action as a class 1 recall, meaning there is a reasonable probability of serious adverse health consequences or death associated with use of the defective units. The update was posted July 2 on the FDA  Website. On May 29, 2012, CareFusion sent an  Urgent Recall Notice  to customers and distributors stating that the company had identified potential risks associated with the Air Life  Infant Breathing Circuit. The action was initiated after the company received complaints of the Y adapter within the breathing circuit developing cracks during patient use. "If a crack develops in the Y adapter, this could potentially result in a leak in the closed ventilation system, leading to a loss in the intended tidal volume delivered to
Post a Comment
Read more

FDA Approves Tapentadol ER for Diabetic Neuropathy

August 29, 2012 — The US Food and Drug Administration (FDA) has approved tapentadol extended-release (ER) ( Nucynta , Janssen Pharmaceuticals, Inc) for the management of neuropathic pain associated with diabetic peripheral neuropathy (DPN) in adults for whom a continuous opioid analgesic is required over an extended time. It is the first opioid to receive this indication, the company notes in a statement today. DPN, the most common type of neuropathy, affects an estimated 16% of the more than 25 million Americans who have diabetes. The condition is often unreported and untreated, with an estimated 2 out of 5 cases not receiving care. Tapentadol ER is already approved for the treatment of moderate to severe chronic pain in adults requiring a continuous opioid analgesic for an extended period. It is a centrally acting synthetic analgesic, although the exact mechanism of action is unknown, the release states. "Although the clinical relevance is unclear," the company n
4 comments
Read more