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Posts Tagged ‘HIV

What can we learn from disease stigma’s long history?

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What can we learn from disease stigma’s long history?.

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Written by huehueteotl

November 27, 2012 at 11:13 pm

Implications Of The New HIV Estimate For India

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The 2007 UNAIDS/WHO AIDS epidemic update recently released has revised the global estimate of HIV/AIDS primarily due to a major reduction of the estimate for India to 2.5 million people living with HIV/AIDS, which is less than half of the previous official estimate of 5.7 million people. This revision is based on new population-based data from the National Family Health Survey in India.

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A commentary published in the Lancet on World AIDS Day by health research experts at The George Institute India, explains the basis of this drop and the implications for future planning of HIV/AIDS control in India. Author Professor Lalit Dandona, Senior Director of The George Institute India and Chair of International Public Health at The University of Sydney School of Public Health, said today, “The data from the recent National Family Health Survey support the findings from similar studies we conducted in southern India, where we showed that the previously used official method for estimation of HIV burden in India was in fact not valid, and led to a 2•5 times higher estimate than what is actually the case.”

Professor Dandona explains that well-designed scientific population-based surveys provide a more reliable representation of HIV in India, compared to the official method used so far, which extrapolated data directly from large public-sector hospitals to the population. “The official method overestimated the burden of HIV in India as the profile of patients visiting large public-sector hospitals is quite different from the population at large, in terms of disease distribution including HIV,” he said.

Professor Dandona believes that the new and much reduced HIV estimate for India has several implications. “We can now see that the official method for annual estimation of HIV prevalence in India needs revision. The new figures show the projected number of people needing HIV treatment over the next decade, and the associated resources needed, will be less than previously anticipated.”

Importantly, the new HIV estimate for India indicates that HIV rates as seen in sub-Saharan Africa will not occur in India, says Professor Dandona. HIV prevention efforts in India should therefore be targeted directly at high-risk groups, such as sex workers, men who have sex with men, mobile populations (migrant labourers and truckers), people with other sexually transmitted infections, and injection drug users. Other areas of focus should include counselling, testing, prevention of transmission from mother to child, and blood-transfusion safety.

In addition, Professor Dandona says the public-health approach for HIV control in India needs to become more scientific. “The establishment of a reliable estimate of HIV burden in India is only an initial step, what’s needed now is more scientific effort to understand the dynamics of HIV spread in India and the impact of interventions on HIV control in India,” he said.
Source: The Lancet – Vol. 370, Issue 9602, 1 December 2007, Pages 1811-1813
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Drop of HIV estimate for India to less than half
Lalit Dandona, Rakhi Dandona

Written by huehueteotl

December 4, 2007 at 12:31 pm

Trauma And Depression May Speed Progression Of HIV

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Even though effective drug cocktails have improved the outlook for many patients with HIV, disease progression, including the time from AIDS onset to death, varies widely from patient to patient. Now, a study led by the University of North Carolina at Chapel Hill School of Medicine provides new evidence that psychological factors play a role in disease progression.

The study is the first-known in the era of highly active antiretroviral therapy (HAART) for HIV to show that traumatic life events, such as physical or sexual abuse, are associated with faster mortality, both from AIDS-related and all causes.

“Trauma and depression are common among people with HIV, and trauma and depression seem to have an effect on disease progression and mortality in HIV. Given that, it is critical that clinicians treating people infected with HIV recognize depression and trauma as risk factors for poor health outcomes, and thus screen and refer patients for psychological and psychiatric treatment when these problems are present,” said Jane Leserman, Ph.D., professor of psychiatry and medicine and lead author of the study.

“Some combination of cognitive behavioral therapy and medication might be very beneficial for patients experiencing severe or multiple types of trauma,” Leserman said.

The researchers interviewed a group of 490 HIV infected patients in the rural southeast. Those who reported a greater number of categories of traumatic life events had faster death from all causes and from AIDS. More than half of the patients in the study experienced three or more lifetime traumas, and half had experienced physical or sexual abuse.

Unlike depression, the effects of which have been more widely studied in the era of HAART, with trauma, it’s possible to establish a time ordering of events.

“In our study, these traumatic events occurred in most cases many years before the progression of the patients’ HIV. So it’s a more compelling argument for a causal effect of trauma,” Leserman said. “Trauma, most of it occurring two or more years before the study, seemed to continue to have a major impact on these patients.”

Leserman hopes to study whether treating HIV patients for trauma results in better health outcomes. “We need further study of trauma treatment in this population to find out if that attenuates some of the negative effects,” she said.

 

Am J Psychiatry. 2007 Nov;164(11):1707-1713.

Relation of Lifetime Trauma and Depressive Symptoms to Mortality in HIV.

Leserman J, Pence BW, Whetten K, Mugavero MJ, Thielman NM, Swartz MS, Stangl D.

Department of Psychiatry, CB 7160, Medical School Wing C, Rm. 233, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7160. jles@med.unc.edu.

OBJECTIVE: In an era of highly active antiretroviral therapies, the authors needed to confirm previous findings showing that stress and depression have an impact on HIV disease progression. The goal of the current study was to examine the effects of lifetime trauma, recent stressful events, and depression on all-cause and AIDS-related mortality among HIV-infected men and women. The authors hypothesized that these psychosocial variables would predict significantly faster HIV-specific and all-cause mortality. METHOD: The authors consecutively sampled HIV-infected men and women who received care at one of eight infectious diseases clinics in five Southeastern states. The sample included 490 patients who were followed by interview for 27 months and followed with their medical records for up to 41 months. RESULTS: There were 29 deaths; 16 were AIDS-related. More lifetime trauma and antigenic marker on helper/inducer T cells (CD4) <200 significantly predicted faster all-cause and AIDS-related mortality. For those at or above the median in trauma, the all-cause death rate was 3.54 per 100 person-years, compared to 1.72 for those below the median. For those at or above the median in trauma, the AIDS-related death rate was 2.13 per 100 person-years, compared to 0.77 for those below the median. Depressive symptoms and higher baseline viral load were significantly related to greater risk of AIDS-related mortality. CONCLUSIONS: Further research is needed to determine if interventions to address trauma and depression can modify these detrimental effects on HIV.

Written by huehueteotl

November 5, 2007 at 10:00 am

Potent Peptides Inhibit HIV Entry Into Cells

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Based in part on protein structures determined at the National Synchrotron Light Source (NSLS) at the U.S. Department of Energy’s Brookhaven National Laboratory, scientists at the University of Utah have developed new peptides that appear to be significantly more effective at blocking HIV’s entry into cells than other drugs in their class.


Structure of D-peptide inhibitors (green, yellow, and purple) bound to an HIV protein mimic in three “pockets” that are essential to the virus’ ability to enter cells. Blocking the pockets thwarts entry and reduces infectivity. (Credit: Image courtesy of DOE/Brookhaven National Laboratory)

In a paper being published online by the Proceedings of the National Academy of Sciences the week of October 8, 2007, the researchers say these peptides are sufficiently potent to begin pre-clinical studies as a new class of agents for the prevention and treatment of HIV/AIDS.

“Our ‘D-peptides’ offer several potential therapeutic advantages over existing peptide entry inhibitors, which are costly, require high dose injections, and suffer from the emergence of drug-resistance,” said University of Utah biochemist Michael S. Kay, lead author on the paper. “In contrast, our D-peptides resist degradation, so they have the potential to be administered by mouth and last longer in the bloodstream. Since these inhibitors have a unique inhibitory mechanism, they should work well in combination with existing HIV inhibitors.”

The researchers were particularly interested in developing drugs to bind to an essential “pocket” structure found in all HIV strains that was previously identified as a promising drug target using structures determined at Brookhaven’s NSLS. Numerous previous attempts to target this pocket failed to produce potent and non-toxic pocket-specific entry inhibitors. In the current work, the researchers used a high-throughput technique to screen a “library” containing hundreds of millions of peptides to identify the rare peptides that would bind to the pocket structure and inhibit HIV entry.

After identifying the most promising candidate peptides, the researchers analyzed the structure of these peptides bound to the target protein using x-ray crystallography at the NSLS. In this technique, researchers analyze how an extremely bright beam of x-rays, available only at synchrotron sources, bounces off and is refracted by the sample to determine the positions of individual atoms. “These structures reveal details of how the peptides bind and guide the development of future inhibitors,” said paper co-author Annie Heroux, a biologist and crystallography specialist at Brookhaven Lab.

This structure-assisted design led to the discovery of D-peptides with up to a 40,000-fold improved antiviral potency over previously reported D-peptides. The structures also suggest ways to engineer the peptides to reduce the chance of drug resistance.

PNAS | October 11, 2005 | vol. 102 | no. 41 | 14759-14764

A human monoclonal antibody neutralizes diverse HIV-1 isolates by binding a critical gp41 epitope

Michael D. Miller, Romas Geleziunas, Elisabetta Bianchi, Simon Lennard, Renee Hrin, Hangchun Zhang, Meiqing Lu, Zhiqiang An, Paolo Ingallinella, Marco Finotto, Marco Mattu, Adam C. Finnefrock, David Bramhill, James Cook, Debra M. Eckert, Richard Hampton, Mayuri Patel, Stephen Jarantow, Joseph Joyce, Gennaro Ciliberto, Riccardo Cortese, Ping Lu, William Strohl, William Schleif, Michael McElhaugh, Steven Lane, Christopher Lloyd, David Lowe, Jane Osbourn, Tristan Vaughan, Emilio Emini, Gaetano Barbato, Peter S. Kim, Daria J. Hazuda, John W. Shiver, and Antonello Pessi

Departments of *Antiviral Research and **Vaccine and Biologics Research, and §§Office of the President, Merck Research Laboratories, West Point, PA 19486; ¶Istituto di Ricerche di Biologia Molecolare “P. Angeletti,” 00040 Pomezia, Rome, Italy; and ||Cambridge Antibody Technology, Cambridge CB 16GH, United Kingdom

Contributed by Peter S. Kim, August 12, 2005

HIV-1 entry into cells is mediated by the envelope glycoprotein receptor-binding (gp120) and membrane fusion-promoting (gp41) subunits. The gp41 heptad repeat 1 (HR1) domain is the molecular target of the fusion-inhibitor drug enfuvirtide (T20). The HR1 sequence is highly conserved and therefore considered an attractive target for vaccine development, but it is unknown whether antibodies can access HR1. Herein, we use gp41-based peptides to select a human antibody, 5H/I1-BMV-D5 (D5), that binds to HR1 and inhibits the assembly of fusion intermediates in vitro. D5 inhibits the replication of diverse HIV-1 clinical isolates and therefore represents a previously unknown example of a crossneutralizing IgG selected by binding to designed antigens. NMR studies and functional analyses map the D5-binding site to a previously identified hydrophobic pocket situated in the HR1 groove. This hydrophobic pocket was proposed as a drug target and subsequently identified as a common binding site for peptide and peptidomimetic fusion inhibitors. The finding that the D5 fusion-inhibitory antibody shares the same binding site suggests that the hydrophobic pocket is a “hot spot” for fusion inhibition and an ideal target on which to focus a vaccine-elicited antibody response. Our data provide a structural framework for the design of new immunogens and therapeutic antibodies with crossneutralizing potential.

Abbreviations: HRn, heptad repeat n; 5H, five-helix; scFv, single-chain variable region fragment; HIVRP, HIV reporter particle; D5, 5H/I1-BMV-D5; T20, enfuvirtide.

Written by huehueteotl

October 12, 2007 at 5:15 pm