Abstract and Introduction
Abstract
Purpose. The most current guidelines issued by the Department of Health and Human Services (DHHS) on the management of human immunodeficiency virus (HIV) infection in treatment-naive patients are reviewed.
Summary. Treatment guidelines are updated frequently because of the emergence of data demonstrating the risks and benefits of antiretroviral therapy. The DHHS guidelines strongly recommend initiating therapy in patients with certain conditions regardless of CD4 cell count and in patients with CD4 cell counts of <350 cells/mm. Although supporting data are less definitive, treatment is also recommended for patients with CD4 cell counts of 350–500 cells/mm. Treatment for patients with CD4 cell counts of >500 cells/mm is controversial. Although cumulative observational data and biological evidence support treatment at higher CD4 cell counts, randomized controlled trial data to support this are not available, and the risk of antiretroviral toxicities, resistance, non-adherence, and cost should be considered in individual patients. The preferred regimens have been consolidated to four options, including a dual-nucleoside reverse transcriptase inhibitor backbone (tenofovir plus emtricitabine) with a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir plus ritonavir or darunavir plus ritonavir), or an integrase strand-transfer inhibitor (raltegravir). Regimens are classified as alternative or acceptable when they have potential safety or efficacy concerns, have higher pill burdens, or require more-frequent administration compared with preferred regimens.
Conclusion. The DHHS 2011 guidelines advocate earlier antiretroviral therapy initiation than recommended in recent years, and preferred regimens have been refined to maximize efficacy, safety, and quality of life for treatment-naive HIV-infected patients.
Introduction
Evidence to guide the treatment of human immunodeficiency virus (HIV)-1 (hereafter referred to as HIV) has been rapidly increasing for over a decade, particularly since the advent of combination antiretroviral therapy in 1996. The goals of antiretroviral therapy are to achieve and maintain viral suppression, prevent morbidity and mortality, restore and preserve immune function, and prevent HIV transmission. HIV treatment is complex and lifelong and usually requires a minimum of 3 antiretroviral drugs from at least two different drug classes to achieve long-term viral suppression. Given the availability of over 20 antiretroviral agents in six different drug classes today, numerous regimens can be created, each with potential advantages and disadvantages that need to be considered in the context of the individual patient. The decision about which regimen to initiate is based not only on safety and efficacy data from clinical trials but also on baseline drug-resistance mutations, adherence-related factors, the potential for drug–drug interactions, and other patient-specific factors.
The data supporting when to initiate antiretroviral therapy are less definitive than the evidence is for which regimen to initiate. CD4 cell count and HIV viral load are surrogate markers used to monitor HIV disease progression before initiating therapy and antiretroviral efficacy after initiating therapy. Advanced HIV disease is associated with immune system deterioration and an increased risk of opportunistic infections and AIDS-defining illnesses, such as pneumocystis pneumonia, toxoplasmosis, and cryptococcosis. Low CD4 cell counts have typically been used as a surrogate marker for immunodeficiency and thus used as a reference for when to start therapy. More recently, morbidity and mortality not related to acquired immune deficiency syndrome (AIDS) have been associated with higher CD4 cell counts, suggesting that treatment should be initiated earlier than previously thought. The benefits and risks of initiating or deferring antiretroviral therapy at various CD4 cell count thresholds should be considered in each patient in order to optimize treatment goals.
First written in 1998 and revised once or twice each year since, the "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents" (hereafter referred to as the guidelines) released by the Department of Health and Human Services (DHHS) contain detailed HIV treatment recommendations based on available data at the time of each revision. Among other topics, the guidelines address the goals of HIV treatment, what antiretroviral drugs to initiate and when to initiate them, antiretroviral combinations to avoid, management of treatment-experienced patients, and the overall therapeutic management of HIV patients. Guidelines for antiretroviral treatment in pregnant women and pediatric patients are available as separate documents and are updated at varying intervals. The recommendations for adults and adolescents have evolved over time based on the emergence of new data, particularly regarding the initiation of antiretroviral therapy and selection of antiretroviral regimens.