AIDSinfo At-a-Glance: Offering Information on HIV/AIDS Treatment, Prevention, and Research, A Service of the U.S. Department of Health and Human Services (DHHS)http://aidsinfo.nih.govinfo.nih.gov is pleased to provide you with a weekly update of highlights about what has happened in the world of HIV/AIDS treatment, prevention, and research. We hope you find this encapsulated view of HIV/AIDS news useful.]]>60<![CDATA[ New Findings Suggest Strategy to Help Generate HIV-Neutralizing Antibodies]]>"New discoveries about anti-HIV antibodies may bring researchers a step closer to creating an effective HIV vaccine, according to a new paper co-authored by scientists at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

"Scientists know that an HIV-neutralizing antibody called b12 binds to gp120, an HIV surface protein, at one of the few areas of the virus that does not mutate: the site where gp120 initially attaches to human immune cells. It was thought that exposing the human immune system to this site on gp120 would generate antibodies that, like b12, can neutralize HIV. Studies have found that for unknown reasons, however, the vast majority of antibodies that recognize this site do not block the virus from infecting cells. Now a new study solves this puzzle, suggesting that antibodies must home in precisely on the site of initial gp120 attachment to successfully neutralize HIV.

"The gp120 protein usually appears on the surface of HIV and on infected cells in inactive forms of viral debris or non-functional viral spikes. Only rarely do gp120 molecules appear on the surface of the virus in a functional viral spike, which contains a cluster of three gp120 molecules, known as a trimer, in specific alignment. HIV uses this functional viral spike to bind to immune cells and infect them.

"The new study shows that most antibodies able to bind to non-functional forms of gp120 cannot bind to gp120 in the functional viral spike and therefore cannot neutralize HIV. ...

"The scientists conclude that generating HIV neutralizing antibodies will require teaching the immune system to make antibodies that precisely target the site of vulnerability on gp120 as it appears in the functional viral spike rather than targeting the plentiful forms of viral debris such as single gp120 molecules."

More information is available:

]]>11/20/2009<![CDATA[ Study Suggests Adenovirus Vector Vaccination Induces Expansion of Memory CD4 T Cells with a Mucosal Homing Phenotype That are Readily Susceptible to HIV-1]]>"In the recently halted HIV type 1 (HIV-1) vaccine STEP trial, individuals that were seropositive for adenovirus serotype 5 (Ad5) showed increased rates of HIV-1 infection on vaccination with an Ad5 vaccine. We propose that this was due to activation and expansion of Ad5-specific mucosal-homing memory CD4 T cells. To test this hypothesis, Ad5 and Ad11 antibody titers were measured in 20 healthy volunteers. … Stimulation of T cells from healthy Ad5-seropositive but Ad11-seronegative individuals with Ad5, or serologically distinct Ad11 vectors induced preferential expansion of adenovirus memory CD4 T cells expressing alpha(4)beta(7) integrins and CCR9, indicating a mucosal-homing phenotype. CD4 T-cell proliferation and IFN-gamma production in response to Ad stimulation correlated with Ad5 antibody titers. However, Ad5 serostatus did not correlate with total cytokine production upon challenge with Ad5 or Ad11. Expanded Ad5 and Ad11 memory CD4 T cells showed an increase in CCR5 expression and higher susceptibility to infection by R5 tropic HIV-1. This suggests that adenoviral-based vaccination against HIV-1 in individuals with preexisting immunity against Ad5 results in preferential expansion of HIV-susceptible activated CD4 T cells that home to mucosal tissues, increases the number of virus targets, and leads to a higher susceptibility to HIV acquisition."

More information is available:

]]>11/20/2009<![CDATA[ Happy Thanksgiving from AIDS<i>info</i>!]]>AIDSinfo At-a-Glance will not be published next week due to the Thanksgiving holiday. We will resume publication the week of November 30.

We wish you and your family a safe and happy Thanksgiving!

]]>11/20/2009<![CDATA[ FDA Releases New Dosing Recommendations for Zidovudine for HIV-Infected Infants]]>“On November 6, 2009, the Food and Drug Administration (FDA) approved revised pediatric dosing recommendations [for Retrovir (zidovudine)] that expand dosing to include children starting treatment at four weeks of age....

“The recommended dosage in pediatric patients 4 weeks of age and older and weighing [4 kg or more] is provided in Table 1. RETROVIR Syrup should be used to provide accurate dosage when whole tablets or capsules are not appropriate.”

More information is available:

]]>11/20/2009<![CDATA[ Study Suggests HLA-B Alleles Target Conserved HIV-1 Proteins]]>“HLA-B alleles of HIV-infected individuals have been shown to have a major impact on their rate of progression toward AIDS, and the T-cell responses they restrict are immunodominant…. We sought to identify whether the association of HLA-B alleles with rate of progression toward AIDS is due to targeting of more restricted and thus more conserved regions of the HIV-1 proteome…. Each residue of the HIV-1 consensus subtype B sequence was coded according to the presence/absence of an epitope, using the compiled epitope data available in the HIV-LANL immunology database. The Shannon entropy for each HXB2 position was calculated using pre-aligned HIV-1 clade B sequences as a measure of its degree of conservation. We then compared the entropy of empty versus epitope-containing positions and HLA-B-restricted versus HLA-A-restricted positions…. Our results suggest that epitopes in HIV-1 targeted by HLA-B alleles lie in more constrained regions of its proteins, in which mutations might have a higher fitness cost and tend to revert. Consequently, HLA-B-restricted cytotoxic T-lymphocyte (CTL) responses may persist longer. This may be one of the factors contributing to the immunodominance and impact of HLA-B-restricted CTL responses on disease progression.”

More information is available:

]]>11/20/2009<![CDATA[ Participate in the AIDS.gov World AIDS Day Conference Call]]>AIDS.gov is hosting a conference call to provide Federal staff and grantees an update on the state of the HIV/AIDS epidemic in the United States and a brief overview of the global epidemic.

Capacity is limited to the first 3,500 callers, and participants must register by November 15. A podcast and transcript will be available shortly after the call on the AIDS.gov Web site.

More information is available:

 

]]>11/20/2009<![CDATA[ Challenges and Approaches to Future HIV Research Outlined]]>“In a new article in Health Affairs, Anthony S. Fauci, M.D. and Gregory K. Folkers, M.S., M.P.H., discuss the urgent imperative both to scale up proven tools of HIV treatment and prevention, and to develop bold new interventions—from curative therapies to vaccines and other new prevention modalities.  Dr. Fauci is director of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health. Mr. Folkers is health scientist and chief of staff in the Immediate Office of the Director, NIAID.

“The authors note that only a fraction of people who need HIV treatment, prevention and related services is receiving them.  Even if access to scientifically proven HIV services were greatly improved by increased funding or improved efficiencies, slowing and ultimately ending the HIV/AIDS pandemic also will likely require major advances in two areas. First, curing a sizable proportion of those already infected with the virus such that lifelong therapy is not required; and, second, developing more powerful prevention tools to slow the rate of new infections. The authors assert that the scientific challenges related to these two goals are the most important issues in HIV/AIDS research today.”

More information is available:

]]>11/20/2009<![CDATA[ Study of Investigational Integrase Inhibitor in Healthy Volunteers Indicates Safety]]>“S/GSK1349572 is a novel integrase inhibitor with potent in vitro anti-HIV activity, a different in vitro resistance profile than other integrase inhibitors, and a favorable preclinical safety and pharmacokinetics (PK).…In the single-dose study, 2 cohorts of 10 subjects (8 active, 2 placebo) received suspension doses of 2, 5, 10, 25, 50 and 100 mg in an alternating panel design. In the multiple-dose study, 3 cohorts of 10 subjects (8 active, 2 placebo) received suspension doses of 10, 25 and 50 mg once daily for 10 days....S/GSK1349572 was well tolerated. Most adverse events (AEs) were mild, with few moderate AEs reported.…PK was linear over dosage range studied.…The half-life was approximately 15 hours.…The PK profile suggests once daily, low milligram doses will achieve therapeutic concentrations.”

More information is available:

]]>11/20/2009<![CDATA[ Larger Foreskin Surface Area Linked to Increased Risk of HIV Infection in Men]]>“Male circumcision reduces HIV acquisition in men. We assessed whether foreskin surface area was associated with HIV acquisition prior to circumcision….In two randomized trials of male circumcision, the surface area of the foreskin was measured after surgery using standardized procedures. Nine hundred and sixty-five initially HIV-negative men were enrolled in a community cohort who subsequently enrolled in the male circumcision trials, provided 3920.8 person-years of observation prior to circumcision. We estimated HIV incidence per 100 person-years prior to circumcision, associated with foreskin surface area categorized into quartiles….Mean foreskin surface area was significantly higher among men who acquired HIV (43.3 cm2, standard error 2.1) compared with men who remained uninfected (36.8 cm, standard error 0.5, P = 0.01)….The risk of male HIV acquisition is increased among men with larger foreskin surface areas.”

More information is available:

]]>11/20/2009<![CDATA[ Volunteer for a Research Study to Help Fight Influenza]]>The National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH) is looking for volunteers to participate in influenza clinical studies. The studies help scientists learn ways to prevent, diagnose, and treat seasonal and pandemic influenza, including H1N1. Clinical studies are available for people with both healthy immune systems and weakened immune systems, which includes individuals who are infected with HIV.

 

Influenza studies are being conducted at the NIH Clinical Center in Bethesda, MD, and at sites across the country. Visit the following Web sites for the latest in NIAID-supported influenza research and detailed information on clinical trials seeking new volunteers:

 

]]>11/20/2009<![CDATA[ Results of Two Studies: Interleukin-2 Plus Antiretroviral Therapy Yields No Clinical Benefit as Compared with Antiretroviral Therapy Alone]]>“Used in combination with antiretroviral therapy, subcutaneous recombinant interleukin-2 raises CD4+ cell counts more than does antiretroviral therapy alone. The clinical implication of these increases is not known. …We conducted two trials: the Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). In each, patients infected with the human immunodeficiency virus (HIV) who had CD4+ cell counts of either 50 to 299 per cubic millimeter (SILCAAT) or 300 or more per cubic millimeter (ESPRIT) were randomly assigned to receive interleukin-2 plus antiretroviral therapy or antiretroviral therapy alone. …The primary end point of both studies was opportunistic disease or death from any cause. ...Over a median follow-up period of 7 to 8 years, the CD4+ cell count was higher in the interleukin-2 group than in the group receiving antiretroviral therapy alone--by 53 and 159 cells per cubic millimeter, on average, in the SILCAAT study and ESPRIT, respectively. ...Despite a substantial and sustained increase in the CD4+ cell count, as compared with antiretroviral therapy alone, interleukin-2 plus antiretroviral therapy yielded no clinical benefit in either study.”

 

More information is available:

]]>11/20/2009<![CDATA[ Study Concludes Survival Disparities are Most Pronounced for Hispanic and Latino HIV-Infected Individuals]]>

"Most persons with human immunodeficiency virus (HIV) infection in the United States present to care with advanced disease, and many patients discontinue therapy prematurely. We sought to evaluate sex and racial/ethnic disparities in life-years lost as a result of risk behavior, late presentation, and early discontinuation of HIV care, and we compared these survival losses for HIV-infected persons with losses attributable to high-risk behavior and HIV disease itself. ...With use of a state-transition model of HIV disease, we simulated cohorts of HIV-infected persons and compared them with uninfected individuals who had similar demographic characteristics. We estimated non-HIV-related mortality with use of risk-adjusted standardized mortality ratios, as well as years of life lost because of late presentation and early discontinuation of antiretroviral therapy (ART) for HIV infection. Data from the national HIV Research Network, stratified by sex and race/ethnicity, were used for estimating CD4(+) cell counts at ART initiation.…The high-risk profile of HIV-infected persons, HIV infection itself, as well as late initiation and early discontinuation of care, all lead to substantial decreases in life expectancy. Survival disparities resulting from late initiation and early discontinuation of therapy are most pronounced for Hispanic HIV-infected men and women. Interventions focused on risk behaviors, as well as on earlier linkage to and better retention in care, will lead to improved survival for HIV-infected persons in the United States.”

 

More information is available:

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