Fwd: e-Newsletter for Tuesday, March 2, 2010

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e-Newsletter for Tuesday, March 2, 2010

HIV and Hepatitis.com Coverage of the

17th Conference on Retroviruses and

Opportunistic Infections (CROI 2010)

More Evidence of Rapid Liver Disease Progression in HIV/HCV Coinfected People, but Antiretroviral Therapy Lowers Risk

By Liz Highleyman

Past research has shown that liver disease typically progresses more rapidly in HIV/HCV coinfected people compared to those with hepatitis C alone, but studies may not be directly comparable and data have not always been consistent.

To shed more light on this issue, Macias and colleagues from several centers in Spain used the transient elastography (FibroScan) method to assess liver fibrosis progression in HIV/HCV coinfected people who were not undergoing treatment for hepatitis C.

Increased fibrosis progression has been observed in studies of HIV/HCV coinfected patients using serial liver biopsies, the researchers explained as background. But because they are invasive, expensive, and uncomfortable, sequential biopsies are not routine, and individuals usually only receive them if disease progression is suspected; thus, serial biopsy recipients are likely not representative of the coinfected population as a whole.

FibroScan uses ultrasound to measure live "stiffness," which is used to estimate fibrosis stage. Though not as accurate as biopsies (especially at distinguishing between intermediate stages), FibroScan is non-invasive and simpler, making it feasible to offer serial fibrosis assessments for all patients. Full Article...

LEDGF/p75 Integrase Inhibitors and

Capsid Assembly Inhibitors Offer

New Approaches for Blocking HIV Replication

In order to replicate, HIV must enter a host cell, shed its outer coat, copy its genetic material (transcribing RNA into DNA, the job of reverse transcriptase), and insert the new copy into the host cell's chromosome (the job of integrase). The virus then "hijacks" the cell's machinery to produce large viral proteins, which are cut up (the job of protease) and assembled into new viral particles.

LEDGF Inhibitors

Frauke Christ from Catholic University in Leuven, Belgium, presented data on a new type of HIV integrase inhibitor that interferes with a cellular protein known as LEDGF (lens epithelium-derived growth factor, or p75). Unlike the approved integrase inhibitor raltegravir (Isentress), this approach does not interfere with the integrase enzyme directly, but rather focuses on its "binding partner," LEDGF/p75.

In 2003, the investigators identified LEDGF/p75 as a strong integrase binding partner, and they have since established a validation procedure for novel HIV cofactors. This allowed them to confirm the importance of LEDGF/p75 -- which tethers HIV integrase to the cellular genome -- in the process of HIV replication.

Understanding another step in the HIV lifecycle, of course, offers a new drug target. X-ray crystallography of the integrase-binding domain revealed that small molecule protein-protein interaction inhibitors could potentially disrupt the LEDGF/p75-integrase interaction. Full Article...

HIV and AIDS - Top New Articles

LEDGF/p75 Integrase Inhibitors and Capsid Assembly Inhibitors Offer New Approaches for Blocking HIV Replication

SUMMARY› While the drug development pipeline is not as full as it has been in recent years, researchers continue to work on new approaches to antiretroviral therapy. Two such novel approaches -- LEDGF integrase inhibitors and capsid assembly inhibitors -- were described in oral presentations at the recent 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010) last month in San Francisco.

ACTG 5202 Shows Abacavir/lamivudine and Tenofovir/emtricitabine Provide Similar HIV Suppression at Low Viral Loads

SUMMARY› Two widely used components of first-line combination antiretroviral therapy (ART) -- abacavir/lamivudine (Epzicom) and tenofovir/emtricitabine (Truvada) -- suppress HIV viral load about equally well when combined with either the NNRTI efavirenz (Sustiva) or the ritonavir-boosted protease inhibitor atazanavir (Reyataz) in people with low baseline viral loads, according to final results from the ACTG 5202 trial reported at the 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010) last month in San Francisco.

ACTG 5202 Sub-study Finds Lipoatrophy Uncommon, Antiretroviral Drugs Have Varying Effects on Bone and Body Fat

SUMMARY› A body composition sub-study of the large ACTG 5202 trial found that different antiretroviral regimens are associated with different types of changes in bone mineral density and body fat, according to a report presented at the 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010) last month in San Francisco. Tenofovir/emtricitabine (Truvada) led to greater bone loss than abacavir/lamivudine (Epzicom), and ritonavir-boosted atazanavir (Reyataz) led to both more bone loss and greater limb and trunk fat gain than efavirenz (Sustiva). But compared with some past regimens, the overall rate of lipoatrophy (peripheral fat loss) in this study was low.

Early Antiretroviral Therapy Reduces HIV Transmission in Discordant Heterosexual Couples

SUMMARY› Starting combination antiretroviral therapy (ART) early -- at CD4 cell counts higher than those recommended by global treatment guidelines -- led to a decrease in HIV transmission between serodiscordant (one positive, one negative) heterosexual couples in Africa, researchers reported at the 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010) last month in San Francisco. One case of transmission did occur from a treated individual, however, indicating that ART does not eliminate risk.

CDC National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Releases New Strategic Plan

SUMMARY› The National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP) last week announced the availability of a new Strategic Plan for the coming 5 years. The 2010-2015 plan describes the agency's overarching goals and strategies for preventing HIV/AIDS, viral hepatitis (hepatitis A, B, and C), sexually transmitted diseases, and tuberculosis.

HIV and AIDS Main Section

HIV/HCV and HIV/HBV Coinfection - Top New Articles

More Evidence of Rapid Liver Disease Progression in HIV/HCV Coinfected People, but Antiretroviral Therapy Lowers Risk

SUMMARY› A study from Spain adds to the evidence that liver fibrosis due to hepatitis C virus (HCV) infection may progress unusually fast in people with HIV. However, the investigators reported at the 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010) last month in San Francisco, effective antiretroviral therapy (ART) that suppresses HIV and raises CD4 cell count reduces the risk of liver disease progression.

Abacavir (Ziagen) Does Not Compromise Effectiveness of Hepatitis C Treatment, but Zidovudine (Retrovir) May Reduce Response

SUMMARY› Using a nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbone containing abacavir (Ziagen, also in the Epzicom coformulation) was not associated with poorer response to interferon-based therapy for hepatitis C in HIV/HCV coinfected patients, researchers reported at the 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010) last month in San Francisco. However, backbones containing zidovudine (AZT; Retrovir) and possibly didanosine (ddI; Videx) were associated with a lower likelihood of achieving a sustained response.

Liver Toxicity in an International Cohort of HIV/HBV Coinfected Patients on Long-term Antiretroviral Therapy

SUMMARY› Lower CD4 cell count and higher hepatitis B virus (HBV) viral load were significant predictors of liver toxicity among HIV/HBV coinfected individuals receiving antiretroviral therapy (ART) in an international study, according to a poster presented at the 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010) last month in San Francisco. These findings support current treatment guidelines recommending earlier ART for HIV positive people with chronic hepatitis B.

HIV/HCV Coinfection Main Section HIV/HBV Coinfection Main Section

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