Key Points

• Primary care physicians with appropriate experience and expertise can provide high-quality care to HIV-infected patients.

• U.S. DHHS guidelines are frequently updated and provide useful direction in treatment of HIV/AIDS patients.

• A few medication combinations should be avoided and certain drugs used with caution in special patient populations.

• Widespread use of HAART has decreased the prevalence of opportunistic infections in HIV/AIDS patients, but prophylaxis is generally advised for specific OIs.

• Once initiated, HAART must be continued indefinitely and lifelong.

The U.S. Department of Health and Human Services

(DHHS) guidelines on the use of antiretroviral agents for HIV-infected adults (December 2009) provide guidance to HIV care practitioners on the optimal use of antiretrovi-ral agents for the treatment of HIV infection in adults and adolescents in the United States. The recommendations are mostly based on studies in peer-reviewed journals (Guidelines Working Group, 2008).

Table 17-3 HIV-Specific Physical Examination

Component of Examination

Area of Relevance

Head, Eyes, Ears, Nose and Throat

Oropharyngeal and gingival exam

Candidiasis and Kaposi's sarcoma

Funduscopy

Cytomegalovirus retinitis

Palpation of thyroid

Risk of anxiety or depression, which can interfere with adherence

Chest

Auscultation for abnormal sounds or for absence of air movement

Pleural effusions, pneumonia, pneumothorax

Abdomen

Hepatomegaly and splenomegaly

Evidence of hepatitis and cause of anemia

Anogenital exam and anal Pap test

Herpes simplex virus, human papillomavirus, or other STDs

Pelvic exam at first visit, in 6 months, and annually thereafter

Cancer, STDs, pelvic inflammatory disease

Baseline Neurologic Examination

Dissociated sensory loss

Peripheral neuropathy

Fine motor skills

Dementia

Muscle strength

Myopathy, neuropathy

Psychiatric

Mental status exam to rule out HIV-associated depression, anxiety, and psychosis

Impact on adherence to medications and appointments

Suicidal thoughts

Need for inpatient care

Behavioral changes

Intracranial pathology, side effects of medications, and laboratory abnormalities

STDs, Sexually transmitted diseases.

Despite the complexity of managing HIV-infected patients, an observational cohort study suggests that family physicians with appropriate experience and expertise in HIV care can provide high-quality care to patients with this complex chronic illness (Landon et al., 2005). Primary care providers without HIV experience, such as those who provide service in rural or underserved areas, should identify experts in the region who will provide consultation when needed. The following goals of therapy have broadened along with knowledge of HIV/AIDS and the epidemiology and long-term consequences of chronic infection:

1. To suppress HIV RNA (viral load) as low as possible (<48 copies/mL), for as long as possible.

2. To preserve or enhance immune function.

3. To delay clinical progression to AIDS.

4. To decrease risk of HIV transmission.

5. To decrease risk of nonopportunistic conditions.

6. To delay the selection of drug-resistant mutations by decreasing the rate of viral replication.

Achieving these goals has resulted in substantial reductions in HIV-related morbidity and mortality and has reduced vertical transmission (Mocroft et al., 1998; Mofenson et al., 1999; Palella et al., 1998, Vittinghoff et al., 1999).

The DHHS guidelines for initiating antiretroviral therapy (ART) include strength of evidence level for each recommendation (Table 17-5). There is strong evidence that patients with CD4+ count less than 200 cells/mm3 and those with a history of opportunistic illness will benefit the most from early ART. It is currently recommended that ART be initiated in patients with CD4+ count of 200 to 350 cells/mm3 (level 1) and 350 to 500 cells/mm3 (level 1/2) (Box 17-4).

Recent data from the ART Cohort Collaboration and North American AIDS Cohort Collaboration on Research and Design (NA ACCORD) suggest that deferring HAART at CD4+ count greater than 500 cells/mm3 was associated with increased risk of mortality. Following this research finding, current guidelines (level 2) recommend initiation of HAART at CD4+ counts of greater than 500. Half the panel members supported this course of action (1) because of the association between non-AIDS-defining illnesses, such as malignancies and liver and kidney disease, and (2) because currently available medications are much better tolerated for longer periods. Drawbacks to this recommendation are (1) the panel did not reach consensus; (2) the benefits of HAART initiation are still unclear; and (3) the results are from observational analyses.

Current antiretroviral medicines include nucleoside/nucle-otide reverse-transcriptase inhibitors (NRTIs), nonnucleoside reverse-transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), CCR5 inhibitors, and integrase strand transfer inhibitors (INSTIs) (Table 17-6). All these groups except one is FDA approved and indicated in

Table 17-4 Routine Laboratory Testing for HIV-Infected Patients antiretroviral-naive patients. FIs are only indicated in antiretro-viral-experienced patients. The latest guidelines provided significant changes from the previous version, especially on what combinations regimen to start in antiretroviral-naive subjects. Current standards of care in antiretroviral-naive patients recommend using three medications (three active agents), combining an NNRTI, a PI, or an INSTI with two NRTIs. This combination of "highly active antiretroviral therapy" has been labeled HAART.

Maraviroc was the only agent excluded by the 2009 guidelines as either a preferred or an alternative agent in antiret-roviral-naive individuals. Maraviroc is a CCR5 inhibitor, comparable to efavirenz in terms of virologic response. Mara-viroc blocks the CCR5 co-receptor but not the CXCR4 co-receptor. At this time, utility of maraviroc is limited because the Trofile test is required to screen for co-receptor use. Mara-viroc will likely be recommended in future guidelines.

The number of preferred PIs was reduced to two: ritonavir-boosted darunavir and ritonavir-boosted atazanavir. Both of these are once-daily options, requiring only 1 capsule of 100 mg of ritonavir to enhance their pharmacokinetics. All other PIs were kept as alternative options for various reasons, including tolerability, toxicity, and efficacy. The dose of ritonavir used to boost PIs exerts negligible antiviral activity. However, it serves the important function of acting as a pharmacokinetic enhancer, increasing drug exposure and prolonging plasma half-life of the combined PI.

In terms of alternative options, it is important to keep in mind that most of these agents are occasionally preferred medications in different settings. A good example is the use of ritonavir-boosted lopinavir in pregnancy. In general, PIs remain valid options to initiate therapy. The PIs as a drug class have been associated with higher rates of adverse gastrointestinal events and potentially cardiovascular events, especially in populations with high cardiovascular risk.

Table 17-5 Recommendations for Initiating Antiretroviral Therapy in Treatment-Naive Adults with Chronic HIV Infection

Measure

Antiretroviral Therapy Recommended (Rating)*

Patients with history of AIDS-defining illness

A

Patients with Asymptomatic HIV Disease:

CD4+ cell count <200/^L

A

CD4+ cell count <350/^L but >200/^L

A

CD4+ cell count <500/^L but >350/^L

A/B

CD4+ cell count >500/^L

B

Other Patients (regardless of CD4+ T-cell count)

Pregnant women

A

Patients with HIV-associated nephropathy

A

Patients co-infected with hepatitis B virus (HBV) when treatment is indicated

B

"Strength of recommendation: A, based on consistent and good-quality patient oriented evidence; B, based on inconsistent or limited-quality patient-oriented evidence; C, based on consensus, usual practice, opinion, and disease-oriented evidence.

Box 17-4 Antiretroviral Regimens for Treatment-Naive Patients

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