The limited ability of most antiretrovirals to cross the blood-brain barrier (BBB, the fibrous bag that encloses the brain and spinal cord) has been a major obstacle to stopping the progressive loss of brain cells caused by HIV. But a new study has found that the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine (Viramune) can penetrate the BBB far better than any other anti-HIV agent. That’s good news, since HIV’s effects on the central nervous system (CNS, the brain and spinal cord) cause neurological problems in about 20 percent of asymptomatic people and an alarming 70 percent to 90 percent of those with more advanced disease.
UCLA’s Michael Wool, MD, says that CNS damage may go unnoticed because “the brain can take a licking and keep on ticking.” Even when symptoms appear—whether minor memory problems and anxiety or more severe forms of thinking dysfunction, depression or mania—they often go unrecognized as HIV related.
One irony of the protease age is that CNS symptoms are increasing in frequency. Why? As PWAs live longer, the brain can become ever more damaged, since drugs that work well in the bloodstream may not in the CNS. That’s because the virus’ drug-resistance mutations may differ between blood and brain. Wool says, “I’ve seen people with undetectable blood levels whose HIV level in the brain is over a million.”
For this reason, Wool recommends always including a minimum of one and preferably two antiretrovirals known to reach the CNS well, adding: “For patients with neurologic problems, spinal fluid should be obtained for viral load and perhaps phenotypic [drug sensitivity] testing that can help guide therapy choices.” Based on research and clinical experience, he believes the best current CNS antiretroviral choices, in descending order of effectiveness, are nevirapine, AZT (Retrovir), d4T (Zerit), 3TC (Epivir) and abacavir (Ziagen).