Patrick Yéni

CONTEXT: Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society-USA panel has updated its recommendations as warranted by new developments in the field. OBJECTIVE: To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIV-infected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described. DATA SOURCES AND STUDY SELECTION: A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel. DATA EXTRACTION AND SYNTHESIS: Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel. CONCLUSIONS: Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/microL and before it declines to 200/microL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced.

OBJECTIVE: To update recommendations for antiretroviral therapy for adult human immunodeficiency virus type 1 (HIV-1) infection, based on new information and drugs that are available. PARTICIPANTS: A 17-member international physician panel with antiretroviral research and HIV patient care experience initially convened by the International AIDS Society-USA in December 1995. EVIDENCE: Available clinical and basic science data including phase 3 controlled trials; data on clinical, virologic, and immunologic end points; research conference reports; HIV pathogenesis data; and panel expert opinion. Recommendations were limited to therapies available (US Food and Drug Administration approved) in 1999. CONSENSUS PROCESS: The panel assesses new research reports and interim results and regularly meets to consider how the new data affect therapy recommendations. Recommendations are updated via full-panel consensus. Guidelines are presented as recommendations if the supporting evidence warrants routine use in the particular situation and as considerations if data are preliminary or incomplete but suggestive. CONCLUSIONS: The availability of new antiretroviral drugs has expanded treatment choices. The importance of adherence, emerging long-term complications of therapy, recognition and management of antiretroviral failure, and new monitoring tools are addressed. Optimal care requires individualized management and ongoing attention to relevant scientific and clinical information in the field.

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 to initiate therapy, choice of initial regimens, patient monitoring, when to change therapy, and how best to approach treatment options, including optimal use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced patients. DATA SOURCES AND STUDY SELECTION: A 14-member panel with expertise in HIV research and clinical care was appointed. Data published or presented at selected scientific conferences since the last panel report (August 2006) through June 2008 were identified. DATA EXTRACTION AND SYNTHESIS: Data that changed the previous guidelines were reviewed by the panel (according to section). Guidelines were drafted by section writing committees and were then reviewed and edited by the entire panel. Recommendations were made by panel consensus. CONCLUSIONS: New data and considerations support initiating therapy before CD4 cell count declines to less than 350/microL. In patients with 350 CD4 cells/microL or more, the decision to begin therapy should be individualized based on the presence of comorbidities, risk factors for progression to AIDS and non-AIDS diseases, and patient readiness for treatment. In addition to the prior recommendation that a high plasma viral load (eg, >100,000 copies/mL) and rapidly declining CD4 cell count (>100/microL per year) should prompt treatment initiation, active hepatitis B or C virus coinfection, cardiovascular disease risk, and HIV-associated nephropathy increasingly prompt earlier therapy. The initial regimen must be individualized, particularly in the presence of comorbid conditions, but usually will include efavirenz or a ritonavir-boosted protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine). Treatment failure should be identified and managed promptly, with the goal of therapy, even in heavily pretreated patients, being an HIV-1 RNA level below assay detection limits.

OBJECTIVE: To provide recommendations for antiretroviral therapy based on information available in mid-1998. PARTICIPANTS: An international panel of physicians with expertise in antiretroviral research and care of patients with human immunodeficiency virus (HIV) infection, first convened by the International AIDS Society-USA in December 1995. EVIDENCE: The panel reviewed available clinical and basic science study results (including phase 3 controlled trials; clinical, virologic, and immunologic end point data; data presented at research conferences; and studies of HIV pathophysiology); opinions of panel members were also considered. Recommendations were limited to drugs available in mid-1998. CONSENSUS PROCESS: Panel members monitor new clinical research reports and interim results. The full panel meets regularly to discuss how the new information may change treatment recommendations. Updated recommendations are developed through consensus of the entire panel at each stage of development. CONCLUSIONS: Accumulating data from clinical and pathogenesis studies continue to support early institution of potent antiretroviral therapy in patients with HIV infection. A variety of combination regimens show potency, expanding choices for initial regimens for individual patients. Plasma HIV RNA assays with increased sensitivity are important in monitoring therapeutic response; however, more data are needed to determine precisely the HIV RNA levels that define treatment failure. Long-term adverse drug effects are beginning to emerge, requiring ongoing attention. Some issues regarding optimal long-term approaches to antiretroviral management are unresolved. The increased complexity in HIV management requires ongoing monitoring of new data for optimal treatment of HIV infection.

CONTEXT: Substantial changes in the field of human immunodeficiency virus (HIV) treatment have occurred in the last 2 years, prompting revision of the guidelines for antiretroviral management of adults with established HIV infection. OBJECTIVE: To update recommendations for physicians who provide HIV care regarding when to start antiretroviral therapy, what drugs to start with, when to change drug regimens, and what drug regimens to switch to after therapy fails. DATA SOURCES: Evidence was identified and reviewed by a 16-member noncompensated panel of physicians with expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care. The panel was designed to have broad US and international representation for areas with adequate access to antiretroviral management. STUDY SELECTION: Evidence considered included published basic science, clinical research, and epidemiological data (identified by experts in the field or extracted through MEDLINE searches using terms relevant to antiretroviral therapy) and abstracts from HIV-oriented scientific conferences between July 2002 and May 2004. DATA EXTRACTION: Data were reviewed to identify any information that might change previous guidelines. Based on panel discussion, guidelines were drafted by a writing committee and discussed by the panel until consensus was reached. DATA SYNTHESIS: Four antiretroviral drugs recently have been made available and have broadened the options for initial and subsequent regimens. New data allow more definitive recommendations for specific drugs or regimens to include or avoid, particularly with regard to initial therapy. Recommendations are rated according to 7 evidence categories, ranging from I (data from prospective randomized clinical trials) to VII (expert opinion of the panel). CONCLUSION: Further insights into the roles of drug toxic effects, drug resistance, and pharmacological interactions have resulted in additional guidance for strategic approaches to antiretroviral management.