Human Immunodeficiency Virus (HIV): Diagnosis and Treatment

Diagnosis

Early diagnosis is important, because early antiretroviral treatment enhances immunologic responses to HIV and likely delays progression to AIDS.

Several tests are available to identify HIV infection:

• HIV RNA viral load is the most sensitive test for identifying primary HIV infection and is also used to follow disease progression. During acute infection, the viral load can be greater than 500,000, but it then falls significantly.
• HIV enzyme–linked immunosorbent assay (ELISA) is positive in 95% of cases within 6 weeks of infection.
• Western blot to identify HIV viral proteins has better than 99% specificity for HIV infection and is generally used for confirmation of a positive ELISA test.
• Assay for the p24 antigen is rarely used because it is less sensitive than testing for HIV RNA.
• CD4+ count is used to monitor the progression of HIV infection: the lower the value, the greater the risk for opportunistic infections. Abnormal complete blood count (CBC) is common and may reveal leukopenia, lymphocytosis, thrombocytopenia, or anemia.

After diagnosis, the CD4+ count and viral load are followed every 3 to 6 months to evaluate the progression of infection and the need for prophylaxis of opportunistic infections.

Screening for other sexually transmitted diseases is necessary, including gonorrhea, chlamydia, syphilis, herpes, hepatitis B, and hepatitis C.

HIV genotype should be obtained to assess for drug resistance, which may be as high as 25%.

Routine follow–up is important, with CBC, creatinine, renal function tests, and liver function tests to evaluate for medication side effects.

Other diagnostic tests are indicated, as necessary, for diagnosis of opportunistic infections (eg, chest x–ray, viral titers).

Treatment

Antiretroviral therapy has significantly improved the prognosis for HIV, reducing progression to AIDS, opportunistic infections, hospitalizations, and mortality. Most patients will achieve full viral suppression within several months of beginning therapy. In general, antiretroviral therapy is initiated in symptomatic patients and in all patients once the CD4+ count falls below 200 cells/mL; therapy should at least be considered and discussed with patients once the CD4+ is less than 350 cells/mL. However, some evidence suggests that early initiation of antiretroviral therapy (within 1 year of seroconversion) regardless of CD4+ count will delay the onset of AIDS; this theory is currently under investigation. Physicians and patients should consider enrollment in a clinical trial to take advantage of experimental therapies.

Antiretrovirals

Classes of antiretroviral agents include nucleoside reverse transcriptase inhibitors (eg, zidovudine, didanosine, lamivudine, stavudine, abacavir), non–nucleoside reverse transcriptase inhibitors (eg, efavirenz, nevirapine, and delavirdine), and protease inhibitors, such as indinivir and ritonavir.

A regimen combining three antiretroviral medications—known as highly active antiretroviral therapy (HAART) or “triple therapy”—is used to avoid or delay drug resistance. Strict adherence is essential.

Once antiviral therapy begins, the CD4+ count and viral load should be assessed every 3 months, along with medication resistance studies.

Prophylaxis

Antimicrobial prophylaxis for opportunistic infections is based on following the CD4+ count to anticipate risk.

Pneumocystis carinii pneumonia: Prophylaxis is usually indicated when CD4+ count falls below 200 cells/mL. Agents include trimethoprim–sulfamethoxazole, dapsone, and pentamidine.

Mycobacterium avium complex: Prophylaxis is usually indicated when CD4+ count falls below 100 cells/mL. Agents include clarithromycin and azithromycin.

Long–Term Antimicrobial Suppression 

Once Pneumocystis carinii pneumonia, cryptococcus, or cytomegalovirus retinitis develops, long–term antimicrobial suppression is recommended.

Exercise

Regular exercise can reduce some side effects of antiretroviral treatment. Aerobic exercise can help reduce total body and visceral fat and normalize lipid profiles in HIV–infected patients.² Combinations of aerobic exercise and progressive resistive exercise (done for at least 20 minutes ≥ 3 times per week) may also lead to significant reductions in depressive symptoms and improvements in cardiopulmonary fitness.³

Psychological Treatment

Psychological approaches can provide benefits for persons with HIV. Although further research is needed to confirm initial findings, available evidence suggests that excessive psychosocial stress can reduce resistance to opportunistic infections in HIV–positive persons. In women with HIV, higher indications of psychosocial stress increased the odds of developing progressive, persistent HPV–related squamous intraepithelial neoplasia 7–fold, compared with women experiencing the least life stress.⁴ Greater stress also accounted for 46% of the variance in recurrence of genital herpes lesions.⁵ Various psychological approaches are significantly associated with decreased viral load,⁶ higher CD4+ cell counts,⁷ and greater adherence to antiretroviral therapy.⁸ HIV–positive men assigned to cognitive–behavioral stress management or active coping interventions were shown to have greater numbers of CD4+ cells.⁹