Neurological AIDS

In 2009, about 2.5 million people worldwide became infected with human immunodeficiency virus (HIV); 33 million are now living with HIV.

Advanced HIV infection is known as acquired immunodeficiency syndrome, or AIDS. The epidemic is still the most intense in sub-Saharan Africa, but it is gaining traction in Asia and Eastern Europe. The impact of AIDS in the United States has been tempered by more widespread use of life-prolonging drugs, making HIV a chronic illness instead of a death sentence. In developing countries, however, only about 36 percent of the people who need therapy are receiving such treatment. In addition, women now represent half of all cases worldwide.

Although the principal target of HIV is the immune system, the nervous system may be affected in varying degrees. HIV-associated neurocognitive disorder (HAND) is a common complication affecting more than 50 percent of people with HIV. HAND also affects those receiving the modern combination antiretroviral treatment (CART), though not to the same degree. Individuals with HAND have mental problems ranging from mild difficulty with concentration, memory, complex decision-making or coordination to progressive, fatal dementia.

Despite advances in treating other aspects of the disease, HAND remains incompletely understood. Most current hypotheses center on an indirect effect of HIV infection related to secreted viral products or cell-coded signal molecules called cytokines. Some proteins of the virus itself are neurotoxic and may play a role in the ongoing damage that occurs during infection. Viral Tat, released by infected cells, has been among the proteins suspected of neurotoxicity. In any case, HIV infection appears to be the prime mover in this disorder because antiretroviral treatment may prevent or reverse this condition in many patients.

Milder forms of HAND have been reported in 30 to 40 percent of HIV-infected people who are medically asymptomatic. In advanced disease, patients can develop increasing difficulty with concentration and memory and experience general slowing of their mental processes. At the same time, patients may develop leg weakness and a loss of balance. Imaging techniques, such as CT and MRI, show that the brains of these patients have undergone some shrinkage. Examination of the brains of persons dying with AIDS can reveal loss of neurons, abnormalities in the white matter (tissue that serves to connect different brain regions), and injury to cellular structures that are involved in signaling between neurons. There also may be inflammation and vessel disease.

Recent studies indicate that highly active combination antiretroviral treatment — cocktails of three or more drugs active against HIV — is effective in reducing the incidence of severe HAND, termed AIDS dementia. Such treatment also can reverse, but not eliminate, the cognitive abnormalities attributed to brain HIV infection.

Peripheral neuropathy, a type of nerve injury in extremities that causes discomfort ranging from tingling and burning to severe pain, is also a major neurological problem commonly seen in HIV patients. It is believed that the virus triggers sensory neuropathy through neurotoxic mechanisms. This reaction has often been unmasked or exacerbated by certain antiretroviral drugs that produce mitochondrial toxicity, which tends to make the neuropathies more frequent and serious. More than half of patients with advanced disease have neuropathy, making it a major area for preventive and symptomatic therapeutic trials.

Despite remarkable advances in new therapies, some patients develop these neurological problems and fail to respond to treatment, thus requiring the development of additional ways to prevent and treat their symptoms. In addition, because of immunodeficiency in HIV patients, otherwise rare opportunistic infections and malignancies are seen more often in those with HIV. Fortunately, however, CART has greatly reduced the incidence of most of these kinds of infections.