Mechanisms of HIV Drug Resistance
Drs. Mark Wainberg and Matthias Götte report on new data concerning the mechanisms of drug resistance from the 4th International Workshop on HIV Drug Resistance and Treatment Strategies in Sitges, Spain.
Experimental Anti-HIV Compounds
Dr. Robert Shafer reports on new resistance data regarding developmental anti-HIV agents from the 4th International Workshop on HIV Drug Resistance and Treatment Strategies in Sitges, Spain.
Immune Reconstitution
Dr. Brian Conway reports from the Immune Reconstitution session of the 4th International Workshop on HIV Drug Resistance and Treatment Strategies in Sitges, Spain.
How and why did the HIV of 3 of 14 HIV-infected Ugandan parturients treated with single-dose nevirapine (NVP) develop NVP resistance-associated K103 mutations? And what does this finding signify with respect to current approaches to preventing vertical transmission of HIV? These questions are explored by Drs. David Katzenstein and Mark Wainberg, respectively:
San Diego County Ryan White CARE Act Program for Resistance Testing - Dr. Michelle Roland discusses the San Diego Office of AIDS Coordination's Ryan White CARE Act I-funded program to provide access to, and payment for, HIV drug resistance testing to HIV-infected patients in San Diego.
Resistance to Protease Inhibitors - Dr. David Katzenstein reports on new and/or enlarged data sets concerning primary and secondary resistance to protease inhibitors (PI). Plus approaches to first-line and salvage therapy using PI- and dual PI-containing regimens.
New Nucleoside Analog Reverse Transcriptase Inhibitors - Dr. Mark Wainberg reports on new NRTI and their potential effectiveness against HIV isolates resistant to other NRTI. New agents include DAPD (a novel dioxolane guanosine analog), tenofovir DF, 3'-fluoro-3'-deoxythymidine (FLT), and several alkylglycerol analogs of forscarnet.
HIV Drug Resistance Testing Policy, Reimbursement and Education Updates: February 2000 - Dr. Michelle Roland takes a look at the new DHHS Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, which are the first U.S. national HIV treatment guidelines recommending the use of drug resistance testing in selected clinical situations. Dr. Roland also provides updates on Aetna's reimbursement policy for HIV drug resistance tests and on the National Association of AIDS Education and Training Centers (NAAETC)'s new HIV drug resistance testing education initiative.
A Critical Assessment of Drug Resistance to New Anti-HIV Drugs in Clinical Development - Dr. Robert Shafer provides a critical look at how investigational antiretroviral drugs, including PIs (ABT-378, tipranavir, and AG1776), NRTIs (PMPA [tenofovir], FTC, F-ddA, and d-OTC), NNRTIs (AG1549, MKC-442, and GW420867X), and the fusion inhibitor T-20, are assessed-and talked about-in terms of their activity against drug-resistant HIV isolates.
FDA Decides Company May Stop Enrolling Clinical Trial: Plans to Down-Regulate Resistance Tests Are Becoming Reality - Dr. Michelle Roland comments on the significance of Visible Genetics' decision to stop enrollment of its SEARCH study, a multi-center, controlled clinical trial of genotyping-assisted antiretroviral therapy, in light of the FDA's recent decision that clinical trial data will not be required for approval of genotypic resistance tests for certain well-defined mutations.
Are the Requirements for FDA Approval of New Drugs Becoming More Stringent? - Dr. Mark Wainberg comments on the FDA's recent decision to deny conditional approval of adefovir for the treatment of HIV disease due to considerations of toxicity, pointing out that such considerations are often outweighed by the ability of adefovir to act effectively in salvage regimens for individuals who have failed all other forms of antiretroviral medication.
Is Hydroxyurea Hazardous to Your Health? - On a global scale, Dr. Mark Wainberg looks at the practical uses of hydroxyurea in the context of the FDA's recent rebuke of Bristol-Myers Squibb for its promotion of Hydrea for the treatment of HIV infection despite two deaths caused by pancreatitis in two patients treated with a combination regimen of d4T/ddI/hydroxyurea.
Roundtable on HIV Drug Resistance Testing - This Roundtable was convened to address 10 key questions pertaining to the current status, development, and future utility of genotypic and phenotypic drug resistance assays in the clinical management of HIV infection. Streaming audio and text presentations are featured.
FDA's CBER Defining Regulatory Requirements for Genotypic Resistance Tests - Dr. Michelle Roland reviews the proceedings of a Medical Device Panel hearing convened in September by the FDA's Center for Biologics Evaluation and Research (CBER) to examine ways to facilitate the development and approval of kit-based genotypic HIV drug resistance assays, while ensuring the quality and consistency of these devices and their use in clinical labs.
FDA Considers the Uses of Resistance Evaluation in New Drug Development and Product Labeling - In a second new article, Dr. Roland digests the proceedings of a two-day workshop held by the FDA, as part of its recent Antiviral Drugs Advisory Committee meeting, to consider requirements for the use of genotypic and phenotypic resistance data in the development and approval of new antiretroviral drugs.
HIV Drug Resistance and International Public Health - Dr. Mark Wainberg provides a concise review of issues, concerns and recent data regarding the emergence of HIV drug resistance in developing countries.
Relationship between HIV-1 Genotype, Phenotype, and Virologic Response - Dr. Robert W. Shafer discusses a session from the 3rd International Workshop on HIV Drug Resistance which details the most current research into the correlations between specific mutations in HIV-1 RT and protease, or genotype, the phenotypic expression of HIV resistance (drug susceptibility), and the response to anti-HIV drug therapy.
Mechanisms of Antiretroviral Resistance - Dr. Mark A. Wainberg discusses a session from the 3rd International Workshop on HIV Drug Resistance that details several studies that examine how mutations in HIV affect the structure and function of RT and proteases to render them resistant to antiviral drugs, as well as how drugs can be adapted to circumvent these effects.
Primary Infection with Drug Resistant HIV-1: Update - Dr. Mayers discusses the recent progress made in developing systems to evaluate the incidence and prevalence of drug resistant HIV-1, as well as the systemic flaws.
Combination Therapy and its Failure - Dr. David Katzenstein examines presentations from the Workshop on Drug Resistance and Treatment Strategies.
New Antiretroviral Drugs - New compounds, and their success against drug-resistant virus, as reported by Dr. Charles Boucher.
Long-Term Suppression/Eradication Strategies - Dr. Brian Conway reports on a variety of studies that investigate the possibility of increasing the efficacy of current regimens.
Second International Workshop on Salvage Therapy for HIV Infection 19 - 21 May 1999, Toronto, Canada - Dr. Mayers reports from different sessions in the workshop, including new agents and regimens for salvage therapy, predictors and mechanisms of therapy failure, responses to specific salvage therapy regimens, the role of diagnostic and monitoring technologies, and clinical trial design. With additional reporting by Nancy Shulman.
Clinical Trial Design for Heavily Pre-treated Patients - Dr. Douglas Mayers reports from a meeting in Toronto that addressed the difficulties inherent in designing clinical trials for patients who are extremely treatment-experienced.
Efavirenz vs. Nelfinavir: ACTG 364 - Dr. David Katzenstein digests the findings of a recently completed study comparing the activity of efavirenz or nelfinavir, or both, in combination with dual NRTI therapy.
Interactions Between Drug Resistance Mutations - How might combinations of viral mutations increase or decrease the overall "fitness" of HIV? Dr. Robert Shafer looks at synergism and antagonism between antiretroviral drug resistance mutations.
Can the 184V Mutation Have Clinical Benefit? - A number of clinical studies suggest that patients who harbor the 184V mutation may continue to benefit from treatment with 3TC. Dr. Mark Wainberg explores the mechanistic bases for this seeming anomaly.
Primary Infection with Drug-Resistant HIV-1 - Dr. Douglas Mayers examines the historical relationship between the expansion of antiretroviral treatment indications and the phenomenon of primary antiretroviral drug resistance.
Abacavir Resistance - Dr. Robert Shafer reviews resistance data on the newest of the nukes.
Improving HIV Therapy with Drug Resistance Genotyping: The VIRADAPT Study - Dr. Jonathan Schapiro reviews the results of the first prospective trial of the utility of genotypic resistance testing in tailoring new treatment regimens for patients failing antiretroviral therapy. Results of the VIRADAPT study were presented at the 4th International Congress on Drug Therapy in HIV Infection in Glasgow, Scotland.
Primary Infection, Primary Resistance - Dr. David Katzenstein discusses the growing problem of primary antiretroviral drug resistance in light of recent prevalence studies presented at the 6th Conference on Retroviruses and Opportunistic Infections in Chicago and earlier reports from the 2nd International Workshop on HIV Drug Resistance & Treatment Strategies in Lake Maggiore, Italy.
Update on Efavirenz - Dr. Robert Shafer reviews new efavirenz-related data presented at the 6th Conference on Retroviruses and Opportunistic Infections in Chicago.
Expert Systems for HIV Resistance Assays - Dr. Jonathan Schapiro explores the development of computer-based expert systems for interpreting genotypic resistance test results.
Antiretroviral Drug ResistanceTesting: The Time is Now! - A Consensus Statement of the HIVresistanceWeb Editorial Board: Charles Boucher, Michael Kozal and Douglas Mayers. "We believe that the time to learn how to use and interpret [antiretroviral drug] resistance assays is now." In light of the abundance of new findings presented at the 2nd International Workshop on HIV Drug Resistance and Treatment Strategies and the 12th World AIDS Conference Drs. Charles Boucher, Michael Kozal and Douglas Mayers present a consolidated view of the readiness of and need for antiretroviral drug resistance testing in the clinical management of HIV infection.
Intensifying Therapy: Is There a Paradigm? - Seeking to inform potential clinical strategies for intensifying anti-HIV therapy, Dr. Michael Kozal takes an in-depth look at recent findings and issues pertinent to the development of an "intensification paradigm".
Sexual Transmission of Multi-Drug Resistant HIV-1 - Following up on HIVresistanceWeb.com's coverage of the 2nd International Workshop on HIV Drug Resistance and Treatment Strategies, Dr. Douglas Mayers reviews the first published report of the sexual transmission of HIV-1 resistant to multiple RTIs and PIs.
