Context New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–infected adults in resource-rich settings. Objective To provide current recommendations for the treatment of adult HIV infection with ART and use of laboratory-monitoring tools. Guidelines include when to start therapy and with what drugs, monitoring for response and toxic effects, special considerations in therapy, and managing antiretroviral failure. Data Sources, Study Selection, and Data Extraction Data that had been published or presented in abstract form at scientific conferences in the past 2 years were systematically searched and reviewed by an International Antiviral Society–USA panel. The panel reviewed available evidence and formed recommendations by full panel consensus. Data Synthesis Treatment is recommended for all adults with HIV infection; the strength of the recommendation and the quality of the evidence increase with decreasing CD4 cell count and the presence of certain concurrent conditions. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions. CD4 cell count and HIV-1 RNA level should be monitored, as should engagement in care, ART adherence, HIV drug resistance, and quality-of-care indicators. Reasons for regimen switching include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Confirmed treatment failure should be addressed promptly and multiple factors considered. Conclusion New recommendations for HIV patient care include offering ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing and choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis.

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Antiretroviral Treatment of Adult HIV Infection: 2012 Recommendations of the International Antiviral Society–USA Panel

Review of recent research on hepatitis C therapy for 54th annual meeting of the American association for the study of liver diseases

This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.

Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.

Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya (R T Lester MD, A Kariri BSc, S Karanja BSc, E Ngugi PhD, L J Gelmon MD, J Kimani, MBChB); Department of Medical Microbiology, University of Manitoba, Health Sciences Centre, Winnipeg, MB, Canada (R T Lester, T B Ball PhD, L J Gelmon, J Kimani, Prof F A Plummer MD); Division of Infectious Diseases, Department of Medicine, University of British Columbia, Vancouver, BC, Canada (R T Lester); School of Kinesiology and Health Sciences, Department of Psychology, York University, York, ON, Canada (P Ritvo PhD); Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada (E J Mills PhD); Department of Global Health, University of Washington, Seattle, WA, USA (M H Chung MD); Department of Economics (W Jack DPhil) and Georgetown Public Policy Institute (J Habyarimana PhD), Georgetown University, Washington, DC, USA; Collaboration for Outcome Research and Evaluation, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada (M Sadatsafavi MD, M Najafzadeh MSc, C A Marra PharmD); University of Nairobi Institute of Tropical and Infectious Diseases, Nairobi, Kenya (B Estambale MBChB); Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Eff ects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial

Eff ects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial

Context The availability of new antiretroviral drugs and formulations, including drugs in new classes, and recent data on treatment choices for antiretroviral-naive and -experienced patients warrant an update of the International AIDS Society–USA guidelines for the use of antiretroviral therapy in adult human immunodeficiency virus (HIV) infection. Objectives To summarize new data in the field and to provide current recommendations for the antiretroviral management and laboratory monitoring of HIV infection. This report provides guidelines in key areas of antiretroviral management: when toinitiatetherapy,choiceofinitialregimens,patientmonitoring,whentochangetherapy, and how best to approach treatment options, including optimal use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced patients.

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Antiretroviral Treatment of Adult HIV Infection

BACKGROUND: The Asian population, in general, has higher antiretroviral concentrations than those who are not Asian, but there are limited pharmacokinetic data for darunavir/ritonavir in Asian children. METHODS: Thai children aged >/=7 years and with body weight (BW)>/=20 kg who were on darunavir/ritonavir for >/=2 weeks underwent 12-h pharmacokinetics with blood sampling before and at 1, 2, 4, 6, 8, 10 and 12 h post-dosing. Darunavir/ritonavir doses were 375/100 mg twice daily (BW 20 to /=40 kg, n=5). Ritonavir 100 mg soft gel capsules were used instead of solution. RESULTS: Of the 19 children, 8 were female, median age was 13 years (range 7-16) and median BW was 29.4 kg. The median duration of darunavir/ritonavir treatment was 11 months. The geometric mean values for darunavir were 60.3 hxmg/l for the area under the concentration-time curve at 0-12 h (AUC(0-12)), 8.3 mg/l for the maximum concentration (C(max)) and 3.1 for the concentration prior to the next dose (C(12)) with no differences between dosing groups. All had C(12) above the protein binding adjusted 50% effective concentration (EC(50)) of protease inhibitor-resistant virus (0.55 mg/l). The darunavir pharmacokinetic parameters were similar to those in non-Asian individuals from the DELPHI study, in which 13 of 20 with BW /=7 years who were on standard darunavir dosing with 100 mg ritonavir boosting had adequate and comparable darunavir AUC(0-12), C(max) and C(12) to non-Asian children who mainly used lower doses of ritonavir boosting. A ritonavir boosting dose of 100 mg can be used for children weighing >/=20 kg, particularly when lower dose formulations are unavailable or if intolerant to the solution.

Vanitha Sekar

Papers

Pharmacokinetics of darunavir/ritonavir in Asian HIV-1-infected children aged ≥7 years.