Because zidovudine is the only antiretroviral available in a parenteral preparation, it is often difficult to continue HAART when a patient cannot take medications by mouth. Drugs given by the enteral route in a hospitalized patient may also be poorly absorbed, and few data exist on the absorption of antiretrovirals administered through a gastrostomy or jejunostomy tube (6).
Prescribing HAART in the Hospital
Antiretroviral prescribing errors occur frequently in the hospitalized AIDS patient. The most common errors include overdosing or underdosing, missing components of multidrug regimens, or missing critical drug-drug interactions (7). Underdosing may lead to resistance, and overdosing contributes to increased toxicity. In one report, prescribing errors occurred in 12% of admissions in the post-HAART era (1998) compared with 2% of admissions in the pre-HAART era (1996) (7). The NRTIs, including didanosine, emtricitabine, lamivudine, stavudine, and zidovudine, require decreased dosing in renal insufficiency. Tenofovir is not recommended for use if the creatine clearance is less than 60 mL/minute. Dosage adjustments in hepatic disease are recommended for amprenavir, fosamprenavir, delavirdine, efavirenz, and nevirapine.
Immune Reconstitution Syndrome
The widespread use of HAART has produced sustained suppression of HIV replication and recovery of CD4 cell counts. It also became evident that HAART resulted in not only a numerical increase in CD4 cells, but also in a functional immune recovery (8-10). This improved T-cell response to antigens results in adequate protection against specific opportunistic infections, allowing for discontinuation of primary and secondary prophylaxis in HIV-infected patients. Immune reconstitution syndrome (IRS), an inflammatory syndrome, is recognized as a potential complication that can occur days to months after starting HAART. The onset of IRS is characterized by a paradoxical worsening of clinical or laboratory parameters despite a favorable response in CD4 cell counts and the suppression of viral replication (9,11,12). IRS has been reported to occur in 10–25% of patients who receive HAART and more commonly in those whose CD4 cell counts are <50 cells/mm3 at the start of HAART (9,11). It is postulated that the inflammatory response is triggered by the recognition of antigens associated with ongoing infection or recognition of persisting antigens associated with past (nonreplicating) infections. Mycobacterial antigens, frequently implicated in IRS, are responsible for about one third of cases. Other antigens associated with IRS include cytomegalovirus and hepatitis B and C (11). In most circumstances, with the management of IRS, HAART should be continued, while specific antimicrobial therapy and steroids should be considered (10).
Medical Conditions that Should Prompt HIV Screening
There are several medical conditions that should prompt screening for HIV infection. Generally, anyone presenting with a fever of unknown etiology who is sexually active or had a blood transfusion prior to 1985 should be screened for HIV infection. Symptoms consistent with acute retroviral syndrome (fever, sore throat, malaise, and skin rash) may be more commonly recognized by clinicians now than previously, and this remains a “golden opportunity” to intervene. Frequently, acute retroviral syndrome will be attributed to Epstein-Barr virus; however, caution should be used in the diagnosis of mononucleosis in those other than teenage populations. It is recommended that all persons presenting with any sexually transmitted disease, unexplained generalized lymphadenopathy, oral candidiasis, or tuberculosis should also be tested. Other conditions where HIV infection should be considered include enigmatic pneumonia, acute hepatitis B infection, herpes zoster infection (particularly in younger, seemingly immunocompetent individuals), idiopathic thrombocytopenic purpura, and nephropathy of unknown cause.
Drug Interactions
Drug interactions are an important consideration in the treatment of HIV infection. Interactions between HAART and other drugs used for the treatment or prophylaxis of opportunistic infections along with those used for the treatment of drug-induced endocrinopathies (hyperlipidemia, diabetes mellitus) are virtually unavoidable. Drug interactions occur either because of drug metabolism or absorption. The multiple metabolic pathways of some drugs make it difficult to predict the outcome of drug interactions. All protease inhibitors and non-nucleoside reverse transcriptase inhibitors are metabolized by the cytochrome P-450 enzyme system and each of these drugs may alter the metabolism of other antiretrovirals and concomitantly administered drugs (13,14). A decrease in trough plasma concentrations of the protease inhibitors to a level below the in vitro concentration required to inhibit replication of 50% of viral strains (IC50) may lead to development of resistance. Because nucleoside analogue reverse transcriptase inhibitors are primarily eliminated by the kidney, they do not interact with other drugs through the cytochrome P-450 system.