Chapter 3
Clinical Management and Opportunistic Infections
 

Antiretroviral Therapy

Antiretrovirals do not eradicate or cure HIV but with therapy, HIV-infected persons can achieve sustained virologic suppression, immunologic reconstitution, preservation of quality of life, and reduction of HIV-related morbidity and mortality.

Initiation of treatment is recommended for patients with AIDS (CD4 <200 regardless of viral load) or symptomatic HIV infection (regardless of CD4 or viral load).  The optimal time to start treatment in patients with asymptomatic HIV infection is not clear.  Current guidelines recommend deferring therapy if the CD4 is above 350/mm3 and if viral load is below 55,000 copies/mL. 

The current guidelines recommend initiation of combination antiretroviral therapy with non-nucleoside reverse transcriptase inhibitor-based or protease inhibitor-based regimens such as the following:

Efavirenz + lamivudine + (zidovudine or tenofovir or stavudine)

Lopinavir/ritonavir + lamivudine + (zidovudine or stavudine)

These medications have potential side effects and drug interactions that clinicians providing HIV care should be familiar with and discuss with the patients.  Some of the complications of antiretroviral therapy are metabolic syndromes e.g. dyslipidemia or hyperglycemia, lipodystrophy or abnormal fat redistribution, lactic acidosis, hepatomegaly with steatosis, osteoporosis, pancreatitis, and cytopenias.

Viral load testing is the best predictor of long-term outcome.  Adherence to antiretroviral regimen predicts durability of virologic response and strategies should be implemented to improve adherence.  Virologic failure is defined as HIV RNA level >400 copies/mL after 24 weeks of therapy, >50 copies/mL after 48 weeks, or >400 copies/mL after suppression of viremia. 

Failure to achieve virologic suppression may result from development of resistance which is assayed through genotypic or phenotypic testing.  Resistance assays help guide choice of antiretroviral therapy but physicians with less experience in their interpretation are encouraged to consult with a clinician with more expertise.

Treatment regimen failure can also be due to immunologic failure defined as failure to increase 25-50 cells/mm³ above the baseline CD4 cell count over the first year of therapy or a decrease to below the baseline CD4 cell count on therapy. Clinical failure is defined as the occurrence or recurrence of HIV-related events (after at least 3 months on an antiretroviral regimen), excluding immune reconstitution syndromes

Updated guidelines for the use of antiretroviral therapy in adults/adolescents, pediatric populations, and for perinatal transmission are available at www.aidsinfo.nih.gov/guidelines.

Table:  Indications for initiating antiretroviral therapy

Table:  Antiretroviral Regimens recommended for treatment naïve patients

Table: Antiretroviral Agents Approved by the FDA

TB and HIV Infection

Tuberculosis (TB) is seen with increasing frequency among persons infected with HIV.  HIV infection is a strong risk factor for progression of TB from latent infection to disease presenting a public health risk if not promptly diagnosed and effectively treated. 

When HIV is first recognized, the patient should receive a tuberculin skin test by administration of purified protein derivative (PPD) by the Mantoux method.  Routine evaluation for anergy is not recommended.  If the skin test is negative, they should be retested every 6 to 12 months.  All HIV-infected persons with a positive PPD skin test (induration of greater than or equal to 5 mm) should have a chest x-ray and evaluation to rule out active tuberculosis. 

If active disease has been ruled out, persons with positive skin test should be given preventive therapy with isoniazid for 9 months.  HIV-infected persons who are close contacts of persons who have tuberculous disease should receive preventive therapy regardless of their PPD skin test result after active disease has been excluded.

Opportunistic Infections

1. Pneumocystis carinii can cause pneumonia (PCP) in persons with HIV.  If the CD4 count is less than 200 cells/mm3 primary prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) should be initiated.  With sulfonamide allergy or intolerance,  alternative medications are dapsone, atovaquone, or aerosolized pentamidine.  Prophylaxis is discontinued if the patient’s CD4 count stays above 200 for more than three months in response to effective antiretroviral therapy.

2. Mycobacterium avium complex (MAC) can cause a disseminated infection in patients with AIDS.  Prophylaxis with clarithromycin or azithromycin is recommended for patients with CD4 counts less than 50/mm3.  Primary prophylaxis can be discontinued when the CD4 count remains >100 for at least three months.

For more details about recommendations on prevention of opportunistic infections refer to the CDC guidelines at www.aidsinfo.nih.gov/guidelines/.

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