Up to 88 percent of people with HIV experience fatigue, and psychological problems appear to be one of the most likely culprits, according to a study published online June 2 in AIDS.

Fatigue has historically been a common problem among people living with HIV, with prevalence rates approaching 90 percent in some studies. Untreated fatigue can lead to unemployment and social isolation, and it can reduce people's ability to effectively care for themselves.

To examine fatigue in HIV disease in the modern treatment era, Eefje Jong, MD, of Slotervaart Hospital in Amsterdam, and her colleagues analyzed data from 42 studies published between January 1996 and August 2008. In addition to wanting to learn more about the prevalence of fatigue in more recent years, the researchers set out to understand the factors—including demographic, physiological, psychological and HIV-specific issues—associated with the condition. They also hoped to gain a better sense of the most effective treatment modalities for the condition.

In previous studies, researchers have found that between 20 and 60 percent of people with chronic HIV infection, and up to 85 percent of people with an AIDS diagnosis, have suffered from fatigue at one time or another. In the studies reviewed for Jong and her colleagues' analysis, fatigue prevalence rates ranged from 33 to 88 percent.

The demographic factors most consistently predictive of fatigue were younger age and unemployment. The authors hypothesized that older people might report less fatigue because they had more effective coping strategies or more time to adjust to medication regimens. Studies that examined race, sex and income were not consistent, though lower income was associated with greater fatigue in at least one study.

In terms of HIV-related issues, CD4 and viral load were not consistently linked with fatigue, though people with more HIV-related symptoms were more likely to have the condition. Studies on comorbid conditions—such as diabetes and hepatitis B or C—were mixed, with some studies finding a connection with fatigue and others showing no connection at all.

Surprisingly, body weight and composition appeared to have no bearing on fatigue, nor did blood levels of proteins related to inflammation, such as interleukin-6 (IL-6) or tumor necrosis factor (TNF) alpha. Some studies showed that lower testosterone levels predicted fatigue, but others did not.

Of all the factors considered, psychological disorders—particularly depression and anxiety—had the strongest and most consistent connection with fatigue. Sleep problems also predicted fatigue. Though the total hours a person slept didn't have an impact, people who napped during the daytime were more likely to suffer with the problem.

Finally, while a number of treatments for fatigue were explored in the studies, medication was not consistently helpful. Medications with the strongest evidence of fatigue treatment were testosterone and psychostimulants, including Adderall (dextroamphetamine) and Ritalin (methylphenidate hydrochloride). Non-medicinal interventions were more helpful, however, especially cognitive behavioral therapy.

Graded exercise therapy (GET) is another possible option to fight fatigue. With GET, a person logs his or her daily activity and increases it to the point where the exercise begins to worsen symptoms. GET has been successful in HIV-negative people with chronic fatigue syndrome, but no good recent studies focused on HIV-positive people. Though exercise and fatigue studies have been conducted in people with HIV, the authors chose not to include any of them in their analysis, because none used a validated instrument for assessing fatigue either before or during the exercise intervention.

“Currently the evidence for interventions with medication is not strong,” the authors said. “Behavioral interventions and GET seem more promising.”

Because fatigue is so common, and so dramatically reduces a person's quality of life, the authors urge care providers to assess their patients for the condition. The researchers state that “in case of fatigue, clinicians should not search only for physical mechanisms, but should question depression and anxiety in detail.”

Finally, the authors are calling on researchers to develop an evidence-based approach to screening and treating fatigue in people with HIV.