New findings show strikingly early seeding of HIV viral reservoir

July 20, 2014

BOSTON - The most critical barrier for curing HIV-1 infection is the presence of the viral reservoir, the cells in which the HIV virus can lie dormant for many years and avoid elimination by antiretroviral drugs. Very little has been known about when and where the viral reservoir is established during acute HIV-1 infection, or the extent to which it is susceptible to early antiretroviral therapy (ART).

Now a research team led by investigators at Beth Israel Deaconess Medical Center (BIDMC) in collaboration with the U.S. Military HIV Research Program has demonstrated that the viral reservoir is established strikingly early after intrarectal simian immunodeficiency virus (SIV) infection of rhesus monkeys and before detectable viremia.

The findings appear online in the journal Nature.

"Our data show that in this animal model, the viral reservoir was seeded substantially earlier after infection than was previously recognized," explains senior author Dan H. Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at BIDMC and steering committee member of the Ragon Institute of MGH, MIT and Harvard. "We found that the reservoir was established in tissues during the first few days of infection, before the virus was even detected in the blood."

This discovery coincides with the recently reported news of the HIV resurgence in the "Mississippi baby," who was believed to have been cured by early administration of ART. "The unfortunate news of the virus rebounding in this child further emphasizes the need to understand the early and refractory viral reservoir that is established very quickly following HIV infection in humans," adds Barouch, a Professor of Medicine at Harvard Medical School.

In this new study, the scientific team initiated suppressive ART in groups of monkeys on days 3, 7, 10 and 14 after intrarectal SIV infection. Animals treated on day 3 following infection showed no evidence of virus in the blood and did not generate any SIV-specific immune responses. Nevertheless, after six months of suppressive ART, all of the animals in the study exhibited viral resurgence when treatment was stopped.

While early initiation of ART did result in a delay in the time to viral rebound (the time it takes for virus replication to be observed in the blood following cessation of ART) as compared with later treatment, the inability to eradicate the viral reservoir with very early initiation of ART suggests that additional strategies will be needed to cure HIV infection.

"The strikingly early seeding of the viral reservoir within the first few days of infection is sobering and presents new challenges to HIV-1 eradication efforts," the authors write. "Taken together, our data suggest that extremely early initiation of ART, extended ART duration, and probably additional interventions that activate the viral reservoir will be required for HIV-1 eradication."
-end-
Study coauthors include first author James Whitney of BIDMC and the Ragon Institute of MGH, MIT and Harvard; BIDMC investigators Srisowmya Sanisetty, Pablo Penaloz-MacMaster, Jinyan Liu, Mayuri Shetty, Lily Parenteau, Crystal Cabral, Jennifers Shields, Stephen Blackmore, Jeffrey Y. Smith, Amanda L. Brinkman, Lauren E. Peter, Sheeba I. Mathew, Kaitlin M. Smith, Erica N. Borducchi; Aliso L. Hill and Daniel I. S. Rosenbloom of Harvard University; Mark G. Lewis of Bioqual, Rockville, MD; Jillian Hattersley, Bei Li, Joseph Hesselgesser, Romas Geleziunas of Gileas Sciences, Foster City, CA; and Merlin L. Robb, Jerome H. Kim and Nelson L. Michael of the Walter Reed Army Institute of Research.

This study was supported, in part, by the US Military Research and Material Command and the US Military HIV Research Program through its cooperative agreement with the Henry M. Jackson Foundation (W81XWH-07-2-0067; W81XWH-11-2-0174); the National Institutes of Health (AI060354; AI078526; AI084794; AI095985; AI096040; AI100645) and the Ragon Institute of MGH, MIT and Harvard.

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School, and currently ranks third in National Institutes of Health funding among independent hospitals nationwide.

BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, Signature Health Care, Beth Israel Deaconess HealthCare, Community Care Alliance, and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Senior Life and is a research partner of Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www.bidmc.org.

Beth Israel Deaconess Medical Center

Related HIV Articles from Brightsurf:

BEAT-HIV Delaney collaboratory issues recommendations measuring persistent HIV reservoirs
Spearheaded by Wistar scientists, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies.

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).

Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.

Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.

The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.

The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.

Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.

NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.

Read More: HIV News and HIV Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.