The opinions and assertions contained herein are those of the authors and are not to be construed as official or as reflecting the views of the Department of Defense, the Department of the Navy, or the naval services at large.
An estimated 850,000 to 950,000 persons in the United States are living with human immunodeficiency virus (HIV), 280,000 of whom are unaware of their infection and another 43,000 of whom meet the definition of acquired immunodeficiency syndrome (AIDS) (www.cdc.gov). The use of highly active antiretroviral therapy (HAART) has produced significant declines in morbidity and mortality from AIDS. Compared with the first 2 decades of the HIV pandemic, the number of HIV-related hospital admissions has declined. However, recently, this rate of decline has markedly slowed (1-3). The reasons for this plateau are many including a steady number of admissions for complications related to HAART, treatment failures, and the overall increased prevalence of HIV infection. Not only will HIV-infected patients still frequently require admission to the hospital, but the complexity of their inpatient care will continue to increase with the advancements in multiple drug regimens, aging of the HIV-infected population, and the interaction of HIV infection with medical comorbidities, many of which are attributable to HAART.
The hospitalist caring for the inpatient with AIDS is presented with several challenges including not only the diagnosis and management of opportunistic infections, but also the complications of HAART. In this article we review the guidelines for the initiation and continuation of HAART in the hospital, review important clinical complications of antiretroviral therapy, and review conditions that may result in the hospitalization of AIDS patients.
Initiation of HAART in the Hospital
In those who do not have access to health care, the initial diagnosis of HIV infection frequently occurs during a hospitalization for an AIDS-defining illness. Initiation of antiretrovirals is contingent on several issues, including CD4 count, viral load, clinical status, likelihood of continued adherence, and the concurrent treatment of opportunistic infections (OIs). All patients with HIV infection and a CD4 count <200 cells/mm3 or an AIDS-defining illness should receive antiretroviral therapy. Controversy exists as to whether a patient admitted for the treatment of an opportunistic infection should begin antiretroviral therapy immediately, or whether this therapy should be deferred until after acute treatment of the OI. The potential detrimental effects of drug-drug interactions, the need for treatment interruptions, and drug-related toxicity between antiretrovirals and OI-specific therapy may support initiating HAART after control of an OI is achieved. Conversely, for some opportunistic infections, such as cryptosporidiosis, the use of HAART is essential for successful treatment of the infection.
An ongoing randomized controlled trial initiated within the Adult AIDS Clinical Trials Group (ACTG) comparing outcomes between patients who start HAART immediately after presentation with an acute OI and patients who start HAART at least 4 weeks after the OI has resolved should help identify the factors supporting early or delayed initiation of antiretrovirals (4).
Generally speaking, HAART can be administered by combining either a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI) with 2 nucleoside reverse transcriptase inhibitors (NRTIs). There are currently more than 20 FDA-approved antiretrovirals. Frequent updates on the guidelines for the use of antiretroviral agents in HIV-infected adults are available at www.AIDSinfo.nih.gov, and a discussion of this topic is beyond the scope of this review.
Continuation of HAART in the Hospital
In most cases, every effort should be made to minimize interruption of HAART during a hospitalization. Although some investigators are examining the virologic and immunologic safety of interrupting HAART as a treatment strategy, there are few data on viral replication, CD4 cell count decline, and rate of acquisition of new mutations in hospitalized patients who have unexpected treatment interruptions (5). The long half-life of some antiretrovirals promotes the emergence of resistance once HAART is stopped. For example, once NNRTIs are stopped, subtherapeutic levels remain in the plasma and cells for several days. HIV then replicates in a milieu that may select for resistance mutations.