Fauci To Present New Insights Into HIV Latency At 12th World AIDS Conference

June 30, 1998

During the past year, scientists have shown that HIV persists in a latent form within a relatively small number of resting CD4+ T cells, even in patients who have received prolonged combination antiretroviral therapy and have no readily detectable virus in their blood. Latently infected CD4+ T cells are potential sources of new viral replication if a patient stops therapy, and pose a formidable obstacle to the goal of eradicating HIV from a person's body, particularly if drug resistance develops.

New data show that latent pools of infected cells are established very early in the course of HIV infection, even if a patient is treated expeditiously with highly active antiretroviral therapy ("HAART" - generally a three- or four-drug combination that includes a protease inhibitor). Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID) and chief of the NIAID Laboratory of Immunoregulation (LIR), will present these and other new findings at the 12th World AIDS Conference in Geneva, Switzerland.

"We have shown that initiating HAART as soon as 10 days after the onset of the symptoms of acute HIV infection does not prevent the formation of a latent reservoir of virus," says Dr. Fauci. "By the time high levels of HIV are detectable in the blood, the virus probably has spread to the lymphoid organs and established a pool of latently infected cells.

"Our group and others are pursuing studies to identify and treat people recently exposed to HIV, before the burst of virus replication, which occurs in most patients soon after infection. Such studies will help determine whether it will be possible to prevent the early establishment of latent pools of HIV."

In Geneva, Dr. Fauci also will discuss the potential for diminishing latent pools of HIV - the possibility of "flushing out" the virus (at least in the test tube) - by stimulating latently infected CD4+ T cells with antibodies to the CD3 molecule on the cell surface, or with combinations of cytokines such as interleukin-2 (IL-2), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha).

"This approach to purging the HIV from latently infected cells assumes that cells activated to release virus will spontaneously die, and the released virus will be prevented from spreading to other cells because of the HAART that the patients are receiving," Dr. Fauci says. "In our in vitro studies, we have shown that it is indeed possible to decrease the number of latently infected cells, but a single round of purging does not completely eliminate the virus.

"Further in vitro studies, as well as clinical trials with HIV-infected patients, will help determine the feasibility of completely eliminating the latent reservoir of HIV-infected cells by repeated, intermittent exposure to activation signals in the setting of HAART," he says.

Dr. Fauci notes that numerous factors are involved in the initiation of HIV infection, in determining levels of viral replication in people infected with HIV, and ultimately, in the rate of disease progression among HIV-infected individuals. Among these are factors intrinsic to the infected individual (the "host"), notably the network of immune signalling molecules (especially cytokines and CC-chemokines) involved in the normal immune response.

"Pro-inflammatory" cytokines such as IL-2, IL-6 and TNF-alpha, boost replication of certain strains of HIV. CC-chemokines such as RANTES, MIP-1alpha and MIP1-beta, can have either a positive or negative effect on HIV replication, depending on the strain of the virus. "The emerging picture of HIV pathogenesis is one of a 'delicate balance' between factors that drive viral replication and those that inhibit the virus," says Dr. Fauci.

When an HIV-infected patient is taking HAART, pro-inflammatory cytokines and other factors which can boost HIV production are still present in their lymph nodes and related organs. However, the powerful effects of HAART can reduce viral replication dramatically, sometimes to the point where HIV can be found only in a latent form within the genes of resting CD4+ T cells. Dr. Fauci and colleagues have shown in vitro that when HAART is withdrawn, the effects of HIV-inducing cytokines and other factors once again promote the active production of virus.

"We feel that these data provide a mechanistic explanation for the clinical phenomenon of rapid viral 'rebound' in many patients with low or undetectable levels of virus in their bloodstream who discontinue HAART. When a patient stops taking HAART because of toxicity or other reasons, or if HIV becomes resistant to the drugs, the virus almost inevitably comes roaring back because latently infected cells are awash in stimulatory factors in the normal environment of the lymph nodes," says Dr. Fauci.

"These data underscore the need to develop comprehensive treatment strategies that not only block HIV replication but also modulate the host factors that drive such replication."

The lead investigators in the NIAID studies to be discussed are Drs. Fauci and Tae-Wook Chun of the LIR. Collaborators include Delphine Engel of the LIR, and Drs. Lawrence Corey and M. Michelle Berrey, and Theresa Shea of the University of Washington in Seattle.

NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.
-end-
Press releases, fact sheets and other NIAID-related materials are available on the Internet via the NIAID home page at http://www.niaid.nih.gov. The home page for the 12th World AIDS Conference is http://www.aids98.ch.
-end-


NIH/National Institute of Allergy and Infectious Diseases

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.