A bacterial DNA motif greatly increases the growth, activation, and maturation of human dendritic cells. Dendritic cells (DCs) are the body's key antigen- presenting cells (APCs). They represent the link between ancient innate immunity and the more complex acquired immune system.
Hydroxyurea (HU) increases the action of other anti-HIV drugs - even against viral strains resistant to those drugs, a new study suggests. HU, an anticancer agent of long standing, inhibits the cellular enzyme ribonucleotide reductase and leads to reduced pools of deoxynucleotide triphosphates (dNTPs).
The protease inhibitor next in line for approval has favorable single-dose pharmacokinetics (PK). Glaxo Wellcome researchers Brian M. Sadler and colleagues studied the PK of amprenavir (formerly known as VX-478 or 141W94) in patients with HIV infection.
A new prime/boost vaccine regimen efficiently induces specific cytotoxic lymphocyte (CTL) responses in the rhesus monkey model of AIDS. The majority of AIDS researchers believe that an effective HIV vaccine must elicit cytotoxic lymphocytes (CTLs). The new regimen achieves exactly that.
A potent new drug may ultimately replace one of the mainstays of AIDS therapy. The new drug is the racemic nucleoside-analog reverse transcriptase inhibitor (NARTI) 2'-deoxy-3'-oxa-4'-thiocytidine (dOTC).
A new member of a potent class of HIV drugs is active against viral strains resistant to other members of the class. The new nonnucleoside reverse transcriptase inhibitor (NNRTI) is costatolide, the isomer of calanolide A previously known as (-)-calanolide B.
As much as has been learned about autoimmune disease, there is exponentially more to know. Researchers trying to develop new immunosuppressive therapies thus have encountered unexpected failure as well as the serendipitous discovery of marketable products.
One episode of unprotected receptive anal sex (URA) has a 0.82 percent risk of transmitting HIV, a new study shows. But don't count on these odds: nine of the 60 study participants who contracted HIV did so after only one or two episodes of URA.
The AIDS virus boards a lipid raft that keeps it afloat as it searches for a way into a cell, a French research team suggests. According to their hypothesis, the raft is made up of glycosphingolipid microdomains. Once it has bound to a CD4 cell receptor, HIV sails along the cell surface on the glycosphingolipid, dragging along the CD4 receptor like a dinghy until it finds an appropriate chemokine coreceptor.
An HIV-2-based gene therapy suppresses HIV-1. University of Michigan researchers Catherine M. Browning, David M. Markovitz, and colleagues have been developing a gene therapy approach to the treatment of AIDS. This approach targets the Tat activation-response (TAR) element of the AIDS virus by causing cells to express TAR decoys.
A dramatic HIV outbreak in rural New York state shows that nobody can safely ignore the AIDS pandemic. It also suggests that HIV transmission may be spread rapidly by individuals who, for reasons that remain unclear, are extraordinarily infectious.
A very highly attenuated, live simian immunodeficiency virus (SIV) vaccine protected two of four monkeys against vaginal challenge with pathogenic SIV. The results are the first good news in a long time for proponents of testing live HIV vaccines.
Immune reconstitution is possible even in AIDS patients with advanced disease, new data indicate. Follicular dendritic cells (FDCs) in lymphoid tissues trap and retain antigens, allowing the development of humoral immunity and the interaction of B and T lymphocytes.
New evidence directly links HIV to thrombocytopenia (TP). TP is one of the major hematopoietic defects seen in patients with HIV infection. It often occurs in the context of bone-marrow invasion by neoplasms or opportunistic infections, but some HIV infected patients develop TP of unknown etiology.
A novel anti-HIV drug works differently than other members of its class. The compound, dubbed RB 2121, attacks the HIV-1 nucleocapsid (NC, or NCp7) protein. Unlike other NC inhibitors, which target NC's unique zinc "fingers," RB 2121 competes with NC for the recognition of its targets.
Mucosal administration of a vaccinia-vectored vaccine can overcome preexisting vaccinia immunity in mice, a National Institutes of Health study demonstrates. The finding breathes new life into vaccines based on recombinant vaccinia virus.
An unexpected problem with AIDS therapy is that highly active antiretroviral therapy (HAART) apparently works too well. The potent drug combinations keep HIV at such low levels that CD4(+) memory T cells all but disappear, a new study shows.
Based on the immunochemical reactivities of their outer envelopes, HIV-1 strains cluster into seven immunotypes. These immunotypes - each distinguished by unique signature peptide sequences - are different from the familiar genotypic classification of HIV-1 into subtypes or clades.
A study of HIV-1 diversity in Kenya challenges current assumptions about HIV transmission, pathogenesis, and virology. Data showing that more than 20 percent of circulating HIV-1 strains in sub-Saharan Africa are intersubtype recombinants suggest that HIV recombinants are either favored for transmission or are formed much more commonly than expected.
Immune- stimulating complexes (ISCOMs) are the best way to formulate HIV envelope antigens, a comparative trial shows. A Dutch/Swedish/U.S. research team compared T-helper immune responses in groups of rhesus macaque monkeys given one of three different envelope-based HIV vaccines.
A newly created virus is expected to speed AIDS research. The new virus affects monkeys much like HIV affects humans. Like its predecessors, the virus is a recombinant chimeric virus created by wrapping the SIV core in the HIV envelope to make a simian/human immunodeficiency virus (SHIV).
Elegant primate experiments point the way to a vaccine that can contain, but not prevent, HIV infection. Monkeys primed with intradermal HIV DNA and boosted with recombinant fowlpox virus (rFPV)-expressed HIV protein developed very low-level infections but remained disease free after challenge with pathogenic SHIV (chimeric virus with an HIV coat over an SIV backbone).
AIDS policy documents from all over the world are now available in a searchable database. The compendium is the first fruit of a five-year project begun in September 1995 and funded by the U.S. Agency for International Development (USAID).
To keep HIV out of the house, it is necessary to lock not just one door but all the doors. New drugs under development block the CCR5 coreceptor used by the so-called R5 HIV strains. R5 HIV is tropic for macrophages and is the type of HIV most frequently transmitted. But in vitro studies now show that these potent drugs rapidly select for R4 HIV strains that enter cells via the alternative CXCR4 coreceptor.
It's not what happens when it works, but what happens when it stops working that may make nelfinavir the best protease inhibitor for first-line use. New in vitro studies show that HIV resistant to nelfinavir is weaker than virus resistant to other HIV protease inhibitors (PIs).
HIV may have armor guarding its Achilles heel. Recent studies appeared to find a weak spot in HIV's defenses: its ability to infect cells was linked to a bridge between the inner and outer domains of its envelope that is conserved across many viral strains (Rizzuto, C. et al., Science, 1998;280:1949-53 and Wyatt, R. et al., Nature, 1998;393:705-11).
A new class of drugs targeting HIV-1 integrase irreversibly inhibits the essential viral enzyme. New studies show that the inhibitors, isolated from the medicinal plants of the Kallawaya people of Bolivia, target the core region of retroviral integrase. These dicaffeoylquinic acids (DCQAs) inhibit HIV replication at concentrations well below cytotoxic levels (see AIDS Weekly Plus, January 25, 1999).
The hurdle may not be as high as had been thought. Evidence from primate studies suggests that intravenous, envelope-based HIV vaccines can more easily protect against mucosal challenge than against intravenous challenge.
Is AIDS the exception to established norms of vaccine-development? No, says Jose Esparza of the Joint United Nations Program on HIV/AIDS (UNAIDS). He suggested that the development of an HIV vaccine is "paralyzed" by issues that have been solved for other vaccines.
Vaccines that elicit cell mediated immunity (CMI) are on the way, predicted 1996 Nobel Prize winner Peter C. Doherty. Doherty and colleague Rolf M. Zinkernagel jointly won medicine's top honor for their discovery that CMI responses are triggered by the T-cell recognition of foreign antigens in the context of the "self" molecules now known as major histocompatibility complex (MHC) antigens.
Heat inactivation appears to increase the antigenicity of HIV, possibly by exposing previously hidden epitopes. The finding comes from a research team using an all-but-abandoned approach to creating an AIDS vaccine: inactivated whole virus. Early efforts to create an inactivated SIV prototype vaccine were abandoned after early failures.
Progress toward an AIDS vaccine has been good, but not very good. That's the assessment of Margaret I. "Peggy" Johnston, and she should know: now assistant director for AIDS vaccines at the National Institute of Allergy and Infectious Diseases (NIAID), Johnston has been the most indefatigable and enthusiastic advocate for HIV vaccine research since the beginning of the epidemic.
A strong promoter is sometimes good, sometimes irrelevant. Developers of DNA vaccines generally want to increase expression of antigenic genes by linking them to strong promoter sequences. In the test tube, this seems best for all vaccines, including HIV vaccines. But now researchers at the U.S. Food and Drug Administration (FDA) have actually explored the effects of promoter strength on an HIV prototype vaccine in a primate model, and their findings come as a surprise.
Monkey studies suggest that prime/boost HIV vaccines may actually be harmful. The most successful candidate HIV vaccine approaches at eliciting anti-HIV antibodies use the so-called prime/boost technique. This approach begins with one or two priming immunizations with a virus-vectored (e.g., canarypox) or DNA-plasmid vaccine followed by booster immunizations with recombinant HIV envelope (Env) protein.
It's easy to overinterpret the large-scale efficacy trials of the VaxGen HIV vaccine (AIDSVax) that recently began with great media fanfare. Politicians point to the trial as an example of Something Being Done. Proponents of traditional empiric vaccine development and their opponents, who insist on a newer lab-based rational approach, see the trial as vindication or as a waste of resources.
A conserved segment of the HIV Gag protein may be a new target for AIDS therapies. HIV-1 Gag plays several vital roles in replication of the AIDS virus. Now mutational analysis of the Gag protein reveals that its capsid region contains a unique proline-glycine-glutamine-methionine (PGQM) amino-acid motif. Without the motif the virus cannot replicate.
They said they would wait for a world-class researcher, and at last one has come. University of Michigan researcher Gary J. Nabel will fill the long-open post of director of the new NIH AIDS Vaccine Research Center.
Can vaccinia virus do for AIDS what it did for smallpox? Researchers at the U.S. National Institute of Allergy and Infectious Diseases (NIAID) think it can. Live, attenuated vaccinia is the basis of the hugely successful smallpox vaccine - and, indeed, gave the world the word "vaccine."
A recombinant encephalitis virus protects monkeys against AIDS and is moving steadily toward human trials. University of North Carolina, Chapel Hill researchers have developed recombinant proviral genomes - known to virologists as replicons - from Venezuelan equine encephalitis virus (VEE; see Vaccine Weekly, June 23, 1997).
It's one step back, two steps forward for a promising AIDS immunotherapy. The idea seems simple: since HIV specific cytotoxic lymphocytes (CTLs) appear to be important in fighting the virus, why not expand a patient's CTL ex vivo and return them to the scene of the crime?
All over the world there are naturally occurring HIV strains resistant to a major part of the AIDS drug arsenal, according to a U.S. Centers for Disease Control and Prevention (CDC) report. The drugs, HIV protease inhibitors, initiated the new era of highly active antiretroviral therapy (HAART) when it was found that in combination with nucleoside reverse transcriptase inhibitors they could reduce virus to undetectable levels.
AIDS occurs when HIV learns to infect naive T cells, a new study confirms. A central mystery to AIDS is why CD4(+) T cells drop precipitously after a long period in which they remain low but relatively stable. Virology studies show that a change in the virus occurs at this time with the appearance of syncytium-inducing strains capable of entering cells via the CXCR4 coreceptor.
Some 25 percent of new U.S. HIV infections already are resistant to at least one AIDS drug. Two separate studies confirm that even before they begin treatment, a surprisingly high number of people already harbor drug- resistant virus. Both reports were made in late-breaker sessions at the 6th Conference on Retroviruses and Opportunistic Infections, held January 31-February 4, 1999, in Chicago, Illinois.
"Can I stop taking some of these pills?" Clinicians face this question for each patient responding to highly active antiretroviral therapy (HAART). When can such a patient cease taking medicines that prevent opportunistic infections (OIs)?
A live, nef-deleted simian immunodeficiency virus (SIV) offered monkeys long-term protection against infection with many different SIV strains. It seems doubtful, however, whether live virus with attenuated replicative capacity can ever be considered safe.
They test negative for HIV but the virus they carry appears normal, although fully infectious. AIDS surveillance by the U.S. Centers for Disease Control and Prevention (CDC) has turned up several people who test negative on most FDA-licensed HIV screening assays and on the usually-definitive Western blot assay.
Bit by bit, a group of research teams are piecing together the parts of an HIV vaccine. It is widely believed that the most effective AIDS vaccine should capable of eliciting HIV specific cytotoxic lymphocyte (CTL) responses. Unfortunately, the genetic diversity of human leukocyte antigen (HLA) alleles means that an epitope that turns on CTL for one person does nothing in another.
Can tying up HIV's two fingers make it a safe vaccine? If so, it might provide the most complete inactivated whole-virus retroviral vaccine yet created. The major question, of course, is whether such a vaccine could be safe.
Could DNA encoding HIV with mutant zinc fingers work as an AIDS vaccine? Yes, according to monkey studies conducted at the U.S. National Cancer Institute (NCI). Three of four animals that received the prototype vaccine remain AIDS free four to five years after challenge with pathogenic simian immunodeficiency virus (SIV).
Soon after it enters the body, HIV appears to hammer a chink in immune defenses. Taking advantage of this early defect in lymphoid cytotoxic lymphocytes (CTLs), new findings suggest, HIV establishes the permanent vantage point from which it disseminates throughout the body and destroys the rest of the immune system.
Small genetic differences may determine whether a person progresses rapidly or slowly to AIDS. The suggestion comes from a study of a single family of macaque monkeys experimentally infected with SIVmac251, a pathogenic strain of simian immunodeficiency virus (SIV).
Don't forget memory. For more than a decade, immunologic studies of HIV disease have focused on the dynamics of effector CD8(+) T cells. But understanding the much smaller pool of HIV specific memory CD8(+) T cells - virtually invisible until recently - now appears to be far more important.
The revolution in AIDS care appears to have missed the inner city. Since March 1996, highly active antiretroviral therapy (HAART) regimens have been available to inner-city residents of Atlanta, Georgia, at an outpatient clinic that is part of the Grady Health System. But after discharge from Grady Hospital, fewer than 15 percent of these patients have visited the outpatient clinic or received HAART.
Sophisticated new tests for drug-resistant HIV may miss important populations of resistant virus, according to the U.S. Centers for Disease Control and Prevention (CDC). Genotypic tests look for specific HIV mutations that confer resistance to various antiretroviral drugs. HIV is so notoriously susceptible to mutation, however, that an infected person harbors not a single strain but a swarm of viral subspecies.
Monkey experiments dramatically demonstrate that CD8(+) T-cell responses determine the course of HIV disease. The studies were presented in a session devoted to cell-mediated immunity at the 6th Conference on Retroviruses and Opportunistic Infections, held January 31-February 4, 1999, in Chicago, Illinois.
Don't try this at home - yet. A daring new treatment strategy hopes that intermittent treatment with highly active antiretroviral therapy (HAART) can lead to permanent immune control of the virus. The strategy comes from several poorly compliant patients whose viral load remained very low after they eventually quit taking the drugs.
What do you call a virus that has no genes? Some researchers are hoping to call it an AIDS vaccine. Recombinant adeno-associated virus (rAAV) is already known by gene-therapy researchers, who are exploring the use of its unique properties as a DNA delivery vehicle. Now vaccinologists hope to take advantage of AAV's unique properties in the quest for today's Holy Grail: an HIV vaccine.
A bold clinical experiment showed that it may be a good idea to flush latent HIV from its hiding place, but that new methods will have to be found. It has become painfully clear that highly active antiretroviral therapy (HAART) regimens cannot eradicate HIV infection because the virus hides out in resting T cells.
Keep on using condoms. That's the urgent advice for people with HIV infection whose viral loads have dropped to undetectable levels due to highly active antiretroviral therapy (HAART). Data collected by the U.S. Centers for Disease Control and Prevention (CDC) show no decrease in the incidence of HIV infection despite the advent of HAART.
Maybe antibodies can do the trick after all. The most difficult problem facing AIDS vaccine researchers is that they don't know what protective immunity to HIV looks like. Studies of highly exposed, uninfected individuals and of people who remain healthy despite long-standing HIV infection indicate that cell- mediated - and not antibody-mediated- immune responses are desirable.
The next AIDS virus may already have jumped from monkeys to humans. This harrowing suggestion comes from French researchers F. Simon and colleagues, who have discovered four new strains of simian immunodeficiency virus (SIV) among three species of monkeys in Cameroon.
How soon a person gets AIDS depends not only on the amount of virus, but also its rate of increase. Soon after HIV infection, the virus and a person's immune system reach an equilibrium - called the viral setpoint - at which viral load remains virtually constant until just before disease progression.
Some people with HIV infection remain negative on HIV antibody tests, a two-year study proves. T. Zhu and colleagues at the University of Washington have found HIV lurking in the resting T cells of some people who remain HIV seronegative All 37 of members of the study cohort continue to test negative for HIV despite repeated high-risk sexual activity with their HIV infected partners.
The U.S. may be on the verge of eliminating mother-to-child HIV transmission, according to a report from the U.S. Centers for Disease Control and Prevention (CDC). A CDC analysis of U.S. HIV/AIDS trends, based on surveillance data collected by June 1998, show dramatic reductions in perinatal AIDS transmission.
The key to AIDS wasting may at last have been found. Wasting of lean muscle mass is such a central feature of HIV disease that AIDS is known as "slim disease" in parts of Africa. Now researchers at Washington University Medical School, St. Louis, Missouri, have found that levels of HIV replication are positively correlated with elevated production of myostatin.
Greater use of an antimicrobial agent will not always be good news for drug manufacturers. A new model using population genetics and epidemiologic observations predicts that the incidence of a drug-resistant pathogen will rapidly increase once the use of a drug to which the pathogen is sensitive exceeds a critical threshold. Reducing consumption below this threshold, the model predicts, will only slowly decrease resistance.
What it is remains unknown, but it seems to protect against HIV infection. Jay A. Levy and colleagues at the University of California, San Francisco, have shown that a soluble factor produced by the CD8(+) T cells can inhibit HIV infection of CD4(+) T cells. Such activity is particularly strong in people who remain asymptomatic despite long-term HIV infection.
New findings suggest that people aggressively treating their HIV infections can take one fewer pill. The most deadly opportunistic infection among western AIDS patients is Pneumocystis carinii pneumonia (PCP). Trimethoprim- sulfamethoxazole (TMP/SMX; cotrimoxazole) is the drug combination of choice for PCP prevention. It is recommended for all HIV infected patients when their T-cell counts fall below 200 cells/(micro)L.
HIV appears to have a skeleton key that lets it escape from a cellular trap for viruses. New studies suggest that taking away this key may be an effective antiviral strategy. The trap is called the 2-5A/RNase L pathway. Viral infection activates this pathway, one of the major interferon-induced antiviral mechanisms.
The bad news continues for proponents of live attenuated HIV vaccines. A steady decline in his CD4 T-cell count has forced a U.S. man naturally infected with nef-deleted HIV - the same deletion used in a prototype AIDS vaccine - to begin taking antiretroviral therapy after 15 years of asymptomatic infection.
The odd cone at the core of HIV is organized like a buckyball. Although it is an asymmetric cone, the HIV nucleocapsid core appears to be highly regular. This suggested to University of Utah researchers Barbie K. Ganser, Wesley I. Sundquist, and colleagues that it is constructed from a regular underlying lattice.
Locally administered DNA immunization can induce immunity in the female genital tract, rat studies show. The finding may lead to new vaccines for sexually transmitted diseases and for contraception. Harvard and University of Massachusetts researchers used Geniva's Accell gene delivery instrument to administer plasmid DNA priming and boosting vaccinations to the vaginal mucosa of female rats.
HIV infected patients are more likely to benefit from influenza immunization when their CD4 T-cell counts are >=200 cells/(micro)L. Yearly flu vaccinations are widely recommended for people with HIV infection. The vaccinations are associated with transient increases in HIV viremia, but no adverse affects of vaccination on disease progression have yet been identified.
Children as old as 5.6 years show no harmful effects from their mother's use of zidovudine (AZT) during pregnancy. The finding strengthens current recommendations that all pregnant women with HIV infection receive AZT during pregnancy. These recommendations are based on the findings of the Pediatric AIDS Clinical Trials Group (PACTG) 076 study, which showed that such AZT use dramatically decreases mother-to-infant HIV transmission.
Two related types of anti-HIV compounds attack the virus in ways different from - and complimentary to - drugs currently in use. The drugs attack the HIV integrase enzyme. Current drugs target the viral reverse-transcriptase or protease enzymes. Because most integrase inhibitors are not specific for the virus, the new compounds have not been on the fast track for drug development.
A long-shot experiment has led to what may be the most important finding in AIDS vaccine research. Like a movie vampire, HIV exposes its fangs only when it is just about to bite into a victim cell. What if you killed the virus at this crucial moment of virus/cell fusion, wondered a University of Montana research team. Could you then obtain a whole-cell vaccine containing occult viral antigens?
It's not their most important concern, but they do think about it. A U.S. Centers for Disease Control and Prevention (CDC) study shows that name-based reporting of people who test positive for HIV may deter some high-risk individuals from being tested.
Do antibodies protect against AIDS? If so, it's hard to see how. Prototype AIDS vaccines can protect cats against feline immunodeficiency virus (FIV). The animals have a robust antibody response to vaccination. But extensive analysis by an Italian research team has failed to identify even a single correlation between humoral immune responses and protection.
What if HIV killed cells as soon as it tried to reproduce within them? A new treatment strategy would do just that. The strategy uses a novel technique to rig a cell's own self-destruction mechanism so that it is triggered by HIV protease - effectively making the cell a death trap for the virus.
They work but they need help. There is a dramatic increase in HIV infected CD4(+) T cells in patients with their own culture-enhanced HIV specific CD8(+) cytotoxic T-lymphocytes (CTLs). This finding underscores the importance of CTLs for control of HIV infection, and has important implications for HIV vaccine development.
Four years of often acrimonious debate may at last have ended. No mere side issue, the debate is about the most important and yet most mysterious phenomenon of HIV infection: the drastic depletion of T cells that heralds AIDS.
It doesn't work all by itself, but it's a big first step. A University of Washington research team reports that a recombinant enzyme derived from the syphilis bacterium - glycerophosphodiester phosphodiesterase or Gpd - is the best single vaccine antigen tested to date.
Vaccination or immune therapy appears to be a needed adjunct to highly active antiretroviral therapy (HAART). Longitudinal studies of eight patients on successful HAART show that HIV specific cytotoxic T-lymphocyte (CTL) responses decay rapidly after treatment. Decay of immune control of HIV may be an important factor in the emergence of drug-resistant virus and treatment failure.
An AIDS patient taking ritonavir died after ingesting the illicit drug known as Ecstasy (3,4-methylenedioxymethamphetamine or MDMA). U.K. physicians reporting the case suggest that all amphetamine derivatives may be dangerous in people taking ritonavir, which inhibits the CYP2D6 liver enzyme responsible for demethylenation.
Stem cells provide a refuge against HIV infection, new data suggests. If so, these important immature cells could be the key to repairing immune systems ravaged by HIV disease. Harvard researchers Hongmei Shen, David T. Scadden, and colleagues report studies confirming that hematopoietic stem cells express the CD4 receptor and CXCR4 or CCR5 coreceptors needed by HIV to infect human cells.
This information is designed to support, not replace, the relationship that exists between you and your doctor.