Magazine article Drug Topics

CNS Accentuating the HIV Treatment Challenge

Magazine article Drug Topics

CNS Accentuating the HIV Treatment Challenge

Article excerpt

After he had taken one of the potent HIV cocktails for a mere month, his previously high plasma viral levels fell below detection, and his CD4 cell counts rose dramatically. Yet this patient was admitted to the hospital because he was unable to walk. A lumbar puncture revealed a viral count of 1.2 million in his spinal fluid.

The case-presented by G. Michael Wool, M.D., at the 28th annual meeting of the American Society of Consultant Pharmacists-is one of many that illustrate the challenge of treating HIV infection in the central nervous system. According to the National Institutes of Mental Health, the incidence of AIDS-related neurologic disease is increasing. Ironically, those statistics have been on the rise despite the declining mortality rates seen from antiretroviral combo therapy.

Wool, an assistant clinical professor at the University of California, Los Angeles School of Medicine, has examined many patients who appear to be treated successfully from the looks of a sinking plasma viral load. But a glance at the skyrocketing viral levels in the cerebrospinal fluid (CSF) offers a grimmer view.

Are antiretrovirals penetrating the blood-brain barrier (BBB)? Wool pointed to studies suggesting that 94% of zidovudine (Retrovir, Glaxo Wellcome) is able to reach the CSF. Supporting data from an abstract presented at the fourth conference on Retroviruses & Opportunistic Infections indicated that only 2% of HIVinfected patients who received zidovudine when it was introduced were diagnosed with AIDS dementia complex (ADC), compared with 36% of untreated patients. But the early success of zidovudine was offset by development of resistance and a subsequent gradual increase in the incidence of ADC.

Wool disclosed that his neurologically disabled patient in the aforementioned case had been receiving zidovudine for a number of years. "Studies show that if you expose HIV to zidovudine for a period of 18 months, 99% of the viral strains will become resistant," he said. And those resistant strains harbor in the plasma as well as the CNS. But the patient's regimen consisted of three drugs, don't the other antiretrovirals get to the brain? Apparently, only some-confirmed by limited neurologic studies-are CNS penetraters. As a consequence, a patient could receive a zidovudine-containing three-drug combo in which two of the drugs may be plasma bound. …

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