HIV and hepatitis virus resistance to antivirals: review of data from the XIX International HIV and Hepatitis Virus Drug Resistance Workshop and curative strategies.

The XIX International HIV and Hepatitis Virus Drug Resistance Workshop offered scientists, clinical investigators, physicians and others an opportunity to present study results selected in a rigorous peer-review process and to discuss those data in an open forum. In 2010, Workshop organizers expanded the programme to include hepatitis B and C viruses, reasoning that workers in all three fields could benefit from shared experience, positive and negative. Slide sessions at the 2010 Workshop focused on hepatitis virus resistance to current and experimental antivirals; epidemiology of HIV resistance; HIV pathogenesis, fitness and resistance; resistance to new antiretrovirals; markers of response to HIV entry inhibitors; HIV persistence, reservoirs and elimination strategies; application of new viral sequencing techniques; and mechanisms of HIV drug resistance. This article summarizes all slide presentations at the Workshop.

Progress in basic and clinical research on HIV resistance: report on the XVIII International HIV Drug Resistance Workshop.

Over nearly two decades, the International HIV Drug Resistance Workshop has become the leading forum for new research on viral resistance to agents developed to treat infection with HIV. The XVIII workshop featured work on HIV type-1 (HIV-1) persistence, reservoirs and elimination strategies; resistance to HIV-1 entry inhibitors (including a comparison of genotyping versus phenotyping to determine HIV-1 coreceptor use before treatment with CCR5 antagonists); polymerase domain resistance to reverse transcriptase inhibitors (including hepatitis B virus and HIV-1 resistance to lamivudine, and emergence of the K65R mutation in HIV-1 subtypes B and C); connection and RNase H domain resistance to reverse transcriptase inhibitors (including the effect of mutations in those domains on response to efavirenz and etravirine); resistance to hepatitis C virus and HIV-1 protease inhibitors; resistance to the integrase inhibitor raltegravir; global resistance epidemiology (including models to predict response to second-line antiretrovirals in resource-poor settings); and the role of minority resistant variants (including the effect of such variants on prevention of mother-to-child transmission of HIV-1). This report summarizes data from the oral abstract presentations at the workshop.

XVII International AIDS Conference: From Evidence to Action - Clinical and biomedical prevention science.

The question of whether to initiate ART at higher CD4+ cell counts than currently recommended by World Health Organization (WHO) treatment guidelines received much attention at the XVII International AIDS Conference (AIDS 2008). If studies presented at the conference ultimately lead to a revision of WHO treatment guidance, the estimated number of people who will need ART globally will increase substantially. Task-shifting is emerging as an important strategy for dealing with the acute shortage of health care workers in many high-burden countries, and several studies presented at AIDS 2008 demonstrated the impressive health system efficiencies garnered by using nurses or other health care providers to deliver HIV care and treatment. Other key presentations and discussion at the conference focused on the optimal time to start TB treatment in HIV-infected patients, the growing risk of resistance in high-burden countries, including its impact on future treatment options, and several large cohort trials testing optimal drug regimens in resource-limited settings.Biomedical prevention research continues to confirm the long-term, protective benefits of circumcision. Several studies involving HIV serodiscordant heterosexual couples have produced data suggesting a strong protective effect of ART for HIV-negative partners. Disappointing results from recent vaccine and non-ARV based microbicides trials are nevertheless providing important data to this field, and the expanding number of pre-exposure prophylaxis (PrEP) trials and ARV-based microbicides appear to provide the best hope for a new, efficacious biomedical prevention intervention.

Perceptions of health, HIV disease, and HIV treatment by patients in 6 regions: analysis of the 2555-person AIDS treatment for life international survey.

BACKGROUND: Antiretroviral therapy (ART) has reached millions of HIV-infected patients worldwide, however very little is known about their perceptions about HIV disease and its treatment. The AIDS Treatment for Life International Survey (ATLIS) is the largest sampling of patient perceptions about HIV disease and its treatment, as well as their behaviors, including HIV status disclosure and ART adherence. METHODS: The International Association of Physicians in AIDS Care (IAPAC) and its survey vendor, Ipsos Insight Health, conducted a convenience-sample survey of 2555 treated and untreated HIV-infected adults recruited by diverse means from 6 regions: North America, Latin America, the Caribbean, Europe, Asia/Pacific, and sub-Saharan Africa. FINDINGS: Nearly three quarters of respondents were taking prescription medications for HIV infection or related diseases. Participants reported generally good overall health and high degrees of satisfaction with current antiretroviral drugs, though approximately half of respondents voiced concern about potential ART toxicity and 39.4% reported switching their antiretroviral regimen specifically because of treatment-associated side effects. About 1 in 5 respondents never took medications for HIV and AIDS. Among the three quarters of respondents currently taking medications, 37% are taking their first prescribed antiretroviral regimen, and 24% have switched from a first-line antiretroviral regimen. Three quarters of respondents believe ART will help them live a long life, and treatment-experienced respondents expressed this view significantly more often than untreated respondents. Large majorities of respondents in Latin America, Asia, and South Africa want to know more about ART, while half or fewer in these countries correctly explained the meaning of undetectable HIV RNA (defined as <50 HIV RNA copies/mL of plasma) or knew their CD4 cell count.

Clinical implications of resistance to antiretrovirals: new resistance technologies and interpretations.

Understanding resistance to antiretroviral therapy plays an ever more crucial role in managing HIV infection as new agents - including several in new antiretroviral classes - promise better control of multidrug-resistant virus in the developed world. Yet these new drugs have different, and often complex, resistance profiles. At the same time, resistance has assumed a key role in developing countries as access to additional antiretrovirals expands in the face of first-line regimen failures. Every year the International HIV Drug Resistance Workshop gathers leading investigators and resistance-savvy clinicians to share unpublished, peer-reviewed research on the mechanisms, pathogenesis, epidemiology, and clinical implications of resistance to licensed and experimental antivirals. The 2007 workshop, held on 12-16 June, proved particularly notable for its exploration of resistance to two new antiretroviral classes, integrase inhibitors and CCR5 antagonists, as well as to agents that control hepatitis C virus (HCV) infection. This report summarizes most oral presentations from the workshop and many posters.

Broad advances in understanding HIV resistance to antiretrovirals: report on the XVII International HIV Drug Resistance Workshop.

The 2008 International HIV Drug Resistance Workshop explored six topics on viral resistance: new antiretrovirals; clinical implications; epidemiology; new technologies and interpretations; HIV pathogenesis, fitness, and resistance; and mechanisms of resistance. The last of these topics provided a forum for new work on resistance of hepatitis B and C viruses, which were also explored in two poster sessions. Much work focused on resistance to the two most recent antiretroviral classes (integrase inhibitors and CCR5 antagonists), a new set of entry inhibitor candidates and one new class represented by the maturation inhibitor bevirimat. Other research explored two novel non-nucleoside reverse transcriptase inhibitors, etravirine and IDX899. Epidemiological work analysed rates of transmitted resistant virus, multiclass resistance in antiretroviral-experienced patients and a heightened resistance risk in injecting drug users regardless of adherence. New research on resistance technologies involved an enhanced assay for HIV-1 coreceptor determination and improved gene-based tools for predicting coreceptor use. In the pathogenesis arena, a small study of intensification shed light on the likely source of residual viraemia in patients on successful antiretroviral therapy. A large study in Mozambique correlated the timing of infant infection with selection, transmission and persistence of nevirapine resistance mutations. Mechanistic research explored resistance to the integrase inhibitor raltegravir, K65R-mediated resistance to tenofovir and the role of connection domain mutations in resistance to zidovudine.

Key reports from the XV International HIV Drug Resistance Workshop 2006.

The XV International HIV Drug Resistance Workshop recorded advances in basic and clinical science of HIV resistance to antiretrovirals as well as new findings on resistance by hepatitis B virus (HBV) and hepatitis C virus (HCV). In the clinical arena, attendees learned of four cases of resistance to lopinavir/ritonavir monotherapy, correlation between low-frequency pretreatment mutations and failure of a first antiretroviral regimen, emergence of non-nucleoside-related mutations in 20% of patients interrupting a suppressive nonnucleoside regimen, and evolution of mutations conferring resistance to an HIV entry inhibitor that is being studied as a vaginal microbicide. New data reported from the POWER 1, 2 and 3 salvage trials suggested that there is a close correlation between darunavir (TMC114) phenotypic susceptibility, the number of baseline protease inhibitor-related resistance mutations and virological response. Scientists exploring the mechanisms of resistance reported of mutations in the carboxy-terminal domain of reverse transcriptase that may further resistance to zidovudine, novel mutations that may contribute to resistance of both nucleoside and non-nucleoside reverse transcriptase inhibitors, and a mechanism that HCV and HIV may share to resist antiviral therapy.

After Toronto, 46th ICAAC offers back to basics.

After the marathon-like challenge presented by the 16th International AIDS Conference held in Toronto a month prior--a challenge that tested the stamina of even the youngest and fittest of conference-goers--the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), held September 27-30, 2006, in San Francisco, was a welcome relief in its staid and singular focus on the presentation of data offering insights into the challenges a variety of patients and their physicians are facing in the second decade of highly active antiretroviral therapy (HAART), as well as reviews of how to make optimal use of antiretroviral regimens constructed from within the existing HAART armamentarium. The big news at this year's ICAAC, however, was on the antiretroviral pipeline, with previews of how a new generation of drugs may help make the difference between life and death for countless millions of men, women, and children living with HIV/AIDS.