Early HAART Initiation Improves Vaccine Response Among HIV-Positive Children

HIV-positive infants who begin treatment with highly active antiretroviral therapy within the first year of life can develop normal immune responses to childhood vaccines, according to a study published online Monday in the Proceedings of the National Academy of Sciences, Reuters Health reports. Vaccines function by stimulating the production of antibodies for a particular disease, but HIV causes a decline in these antibody-producing cells and therefore reduces immunity. Prior to the new study, researchers were unsure whether the timing of HAART initiation could help preserve these cells and promote normal immune responses to vaccines among children.

For the study, Paolo Rossi of the University of Tor Vergata in Rome and colleagues examined 70 children who contracted HIV through mother-to-child transmission and 50 HIV-negative control participants. Of the HIV-positive children, 13 received HAART during their first year, six received no treatment and the remaining children received therapy later in life. All of the children in the study group received the recommended vaccinations for measles and tetanus. According to the study's findings, children who received HAART during their first year maintained normal levels of antibody producing cells, while children in the other groups had lower levels of these cells.

According to Rossi, the timing of HAART initiation is a key factor in determining whether HIV-positive children will develop normal vaccine responses and how long the response will last. The authors write that their findings support early HAART initiation for the purpose of preserving normal immune responses among HIV-positive infants. However, they add that health officials might need to revise vaccine schedules for HIV-positive children who begin treatment after the first year of life (Reuters Health, 4/29).

An abstract of the study is available online.

Delaying HAART Might Prevent Complete Immune System Recuperation

People living with HIV who do not start highly active antiretroviral treatment until their CD4+ T cell counts drop below 200 might not be able to reach a normal CD4 cell count, even after 10 years of otherwise effective treatment, according to a study in the March 15 issue of Clinical Infectious Diseases, Reuters reports. According to Reuters, an HIV-positive person is considered to have a normalized immune status after CD4 counts are maintained above 500.

For the study, researchers examined 366 HIV-positive people who had maintained plasma HIV RNA levels of no more than 1,000 copies per milliliter of blood for at least four years after starting therapy. About 25% of the study's participants were followed for more than 10 years, with a median follow-up of 7.5 years. Reuters reports that 95% of the participants who started therapy with a CD4 cell count of at least 300 were able to reach a normalized CD4 cell count of at least 500. The researchers reported that 44% of participants who began treatment with a CD4 cell count of less than 100 -- as well as 25% who began treatment with a CD4 cell count of between 100 and 200 -- were not able to reach a CD4 cell count higher than 500.

Lead author Steven Deeks of the University of California-San Francisco and colleagues wrote that a "persistently low CD4 cell count during treatment is associated with increased risk of both AIDS and non-AIDS related events," such as liver disease, cardiovascular disease and cancer. They added that "novel immune-based therapeutic approaches may be necessary to restore immunocompetence in these individuals." In a related editorial, Boris Julg and Bruce Walker, both of Massachusetts General Hospital, wrote that major treatment guidelines recommend beginning antiretroviral therapy when CD4 cell counts drop below 350, adding that it can be difficult for developing and low-income countries to follow such advice. Julg and Walker wrote that "adequate early therapy, leading to more-complete immune reconstitution, may save resources because of the resulting lower incidence of opportunistic infections and reduced need for medical care" (Reuters, 4/7).

An abstract of the study is available online. An abstract of the accompanying editorial also is available online.

Antibodies Present in Long-Term HIV Survivors Could Contribute to Vaccine Development

HIV-positive people who do not develop AIDS and do not require antiretroviral medication could provide insight for new strategies in vaccine development, according to a study published Sunday in the journal Nature, London's Independent reports. Michel Nussenzweig -- head of Rockefeller University's Laboratory of Molecular Immunology and author of the study -- said his research aimed to harness natural mechanisms to target HIV rather than use synthetically produced antibodies, some of which have failed in earlier HIV vaccine trials.

For the study, Rockefeller University researchers examined antibodies present in the blood of six long-term HIV survivors who appeared to have a degree of natural immunity to the virus (Connor, Independent, 3/16). The researchers isolated 433 antibodies from the patients, all of which targeted HIV's protective outer coating, or "envelope." The researchers then cloned the antibodies and observed which elements of the envelope each antibody targeted and how effectively it neutralized HIV. During the research, Johannes Scheid, a doctoral student at Rockefeller University, identified a new structure on the HIV envelope that scientists previously had not recognized as an antibody target. Although the researchers determined that each antibody individually had a weak effect on HIV, they also found that the antibodies as a group effectively targeted the virus (PA/Google.com, 3/15). In addition, the researchers determined that a prototype vaccine developed from several of the antibodies can prevent the growth of HIV in human cells in a test tube.

Nussenzweig said the study identified "many different antibodies that individually have limited neutralizing ability but together are quite powerful." According to Nussenzweig, only about one in every 1,000 HIV-positive people produces the neutralizing antibodies. He said the research attempts a new approach to HIV vaccine development by "copying what exists in nature and that we know can work because of the long-term survivors." He added, "Instead of inventing something that doesn't exist, it's trying to copy something that does exist." Nussenzweig said the study's results "should make people think about what an effective vaccine should look like." According to the Independent, the researchers next plan to conduct further trials of vaccine candidates on laboratory animals and human volunteers.

The Independent also profiled Kai Brothers, a San Francisco man who has been living with HIV for 28 years without developing AIDS or requiring antiretroviral medications. The Independent reports that Brothers, who did not participate in the new study, might be one of "a few -- perhaps as few as one in 5,000" -- HIV-positive people who have natural immunity to the virus. Brothers said he has participated in HIV research for 10 years, adding, "I feel dedicated to giving back something because of my good fortune" (Independent, 3/16).

An abstract of the study is available online.

Microbicide Containing Natural Compound Provides Protection in Monkeys Against Simian Version of HIV

An experimental microbicide containing a naturally occurring compound provides protection in monkeys against the simian version of HIV by diminishing immune responses to the virus, according to a study published Wednesday in the journal Nature, the Los Angeles Times reports. HIV typically spreads in the body by entering CD4+ T cells, which the immune system sends out to attack the virus after exposure. The compound -- called glycerol monolaurate, or GML -- works by inhibiting immune signals that dispatch the T cells to attack the infection. It is those T cells that HIV infects and uses to proliferate throughout the body (Engel, Los Angeles Times, 3/5). GML occurs naturally in the human body and already is approved for use as an antimicrobial and anti-inflammatory ingredient in cosmetics and toiletries, as well as an emulsifier in foods. In addition, each dose of GML used in the study costs less than one cent. According to the researchers, the study's findings have promising implications for the development of effective microbicides to prevent HIV (AFP/Google.com, 3/4).

For the study -- led by Ashley Haase, head of the microbiology department at the University of Minnesota Medical School, and microbiologist Patrick Schlievert -- researchers administered the GML gel vaginally to five rhesus monkeys and then repeatedly exposed them to the simian version of HIV, or SIV. After two weeks, all of the five monkeys tested negative for the virus. However, four out of five monkeys that did not receive the GML gel contracted SIV. According to the researchers, five months after the experiment, they learned that one of the monkeys treated with GML tested positive for the virus. The researchers said they are unsure how this monkey contracted SIV, but they suggested that a small amount of the virus might have spread in the body undetected or the monkey might have been exposed to SIV after the study ended (Lerner, Minneapolis Star Tribune , 3/4).

Haase said the current research is "a relatively preliminary study but worth sharing because it establishes a novel approach." The researchers added that a mathematical model suggests that even if the microbicide were 60% effective and used 20% of the time, it still could prevent about 2.3 million HIV cases over a three-year period. According to the study authors, researchers will need to conduct further animal studies to determine whether the microbicide should be administered over a longer period of time to provide long-term protection against the virus (Los Angeles Times, 3/5). Further study also will be needed to demonstrate whether GML prevents HIV transmission among humans, they added. The researchers said they plan to undertake a larger study with monkeys, followed by a study with female volunteers. In addition, the University of Minnesota has applied for patents for the new compound combining GML with a personal lubricant, which currently is not available commercially. According to Schlievert, the ultimate goal will be to develop a gel that can be used for both men and women (Minneapolis Star Tribune, 3/4).

According to the study authors, the research "represents a highly encouraging new lead in the search for an effective microbicide to prevent HIV transmission that meets the criteria of safety, affordability and efficacy" (Fox, Reuters, 3/4). Haase said that although the research "sounds counter-intuitive, halting the body's natural defense system might actually prevent transmission and rapid spread of the infection" (AFP/Google.com, 3/4). Charlene Dezzutti, laboratory network director of the Microbicides Trial Network at the University of Pittsburgh, said the research illustrates "a new approach to thinking about microbicides." She added that she believes scientists "definitely" could develop an effective microbicide before developing an HIV/AIDS vaccine. "It's just a matter of getting all the right pieces together," she said (Lauerman, Bloomberg, 3/4). Rowena Johnston, vice president of research for the Foundation for AIDS Research, said that if further studies confirm these results, "then this is really a fabulous new finding." She said that although future microbicide research could encounter setbacks, the study is "absolutely a great beginning to a research project."

According to Schlievert, women could apply the GML microbicide "an hour or so before they had sex" to protect against HIV transmission. In addition, the gel might provide protection against other sexually transmitted infections, such as chlamydia, he said (Minneapolis Star Tribune, 3/4). According to AFP/Google.com, Schlievert first identified the microbicidal properties of GML when studying the use of the compound in preventing toxic shock syndrome associated with tampons. He said research repeatedly has found that the compound is safe and has no effect on beneficial vaginal bacteria (AFP/Google.com, 3/4). Lorraine Teel, executive director of the Minnesota AIDS Project, said the gel could provide women with a way to prevent disease transmission in areas of the world where many people do not use condoms because of cultural or other pressures. The research has "absolutely enormous implications" for women worldwide, she said (Minneapolis Star Tribune, 3/4). Anthony Fauci, director of NIH's National Institute of Allergy and Infectious Diseases, said an effective microbicide would "empower women to protect themselves in a sexual situation in which they may not have complete control" (Los Angeles Times, 3/5).

An abstract of the study is available online.

New Blog at AIDS-Drugs-Online.com

The staff at www.aids-drugs-online.com have started up another blog! This blog is a great resource, and is featuring all of the latest articles and press releases that ADO.com has put out. It will contain up-to-date news and information and be a great resource (not unlike this one) for those looking for information on HIV and AIDS.

The new blog can be found at: AIDS-Drugs-Online.com/wordpress/