After initial diagnosis, HIV-positive patients are usually referred to specialists in HIV treatment. Experts in HIV treatment can be family practitioners, internists, or infectious disease specialists. In addition to physicians, many nurse practitioners and physician assistants are experts in HIV treatment. The quality of care provided seems to correlate with the number of HIV-positive patients treated by a practitioner, not his or her specialty or profession.18
The first step in assessing a newly diagnosed patient is measuring the CD4 cell count. Normal values for CD4 cells vary by laboratory, but usually range from 500 to 200 cells/mL. The decision to begin antiretroviral therapy usually is based on a patient’s CD4 cell count. Antiretroviral medications generally are started if a patient’s CD4 count is less than 350 cells/mL. However, medications can be started at higher CD4 counts if a patient is having symptoms thought to be related to HIV viremia. Additional elements that are considered are the patient’s willingness to start medication and the state of other concurrent medical or psychosocial conditions.
More than 25 antiretroviral medications have been approved for HIV treatment. Only 4 medications were approved between 1987 and 1995, with the majority approved more recently. These drugs are classified by the enzyme or protein they target in the HIV life cycle. The mainstay of therapy consists of drugs from 3 classes of antiretroviral drugs: nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). HAART usually consists of 3 drugs: 2 NRTIs and either 1 NNRTI or 1 PI. HAART gained acceptance as the standard of care for antiretroviral treatment in 1996 because it demonstrated potent and durable suppression of viral replication.
Three additional classes of antiretroviral medications have been developed, but currently are used for patients who have resistance to first-line drugs. Fusion inhibitors block the interaction of HIV surface proteins with the CD4 cell surface. CCR5 receptor antagonists block the human CCR5 protein from attachment by HIV. Finally, integrase inhibitors prevent the insertion of HIV DNA into the human DNA.
Advances in antiretroviral therapy have translated into less burdensome medication regimens with fewer side effects and less burdensome dosing schedules. The majority of treatment-naïve patients have the opportunity to take once-daily medication regimens, with a pill burden as low as 1 pill per day using multidrug combination formulations. Consequently, many antiretroviral medications with high rates of adverse effects and difficult dosing schedules have fallen out of favor.
Testing for resistance to HIV medications typically is performed in each patient prior to initiating antiretroviral therapy. Genotype tests identify genetic mutations in the viral genome that confer resistance to antiretroviral mutations. Approximately 10% to 18% of treatment-naïve patients have such resistance mutations, in most cases indicating that they were infected with an HIV strain already resistant to some medications. 19,20,21
Resistance is one of many factors considered when selecting antiretroviral medications for initial therapy. Other factors to consider when constructing a medication regimen include interactions with other medications, other medical conditions, dosing schedules, and the side effects of each antiretroviral medication. ( lists some adverse effects associated with antiretroviral medications.) In addition, a patient’s personal circumstances, such as work schedules, specific intolerances, and ability to pay for medications, need to be considered. In general, the potency of a candidate antiretroviral regimen must be balanced against its tolerability and feasibility for a particular patient, and consequently, his or her ability to adhere to the regimen. High levels of adherence are crucial to increase the likelihood of long-term viral suppression.22,23,24
Adverse Effects Associated With Antiretroviral Medications
For patients taking antiretroviral drugs, routine clinic visits are necessary to monitor adherence, to identify and address adverse effects of antiretroviral medications, and to perform laboratory tests to evaluate virologic and immunologic responses to antiretroviral therapy. The 2 most important prognostic indicators are the patient’s CD4 cell count and the level of viral RNA circulating in the blood (plasma viral load). The goal of treatment is to suppress the viral load below the level detectable by current laboratory assays. Although viral levels may be “undetectable” in the blood, HIV remains integrated within the DNA of several types of immune cells, including the long-lived memory T cells. If antiretroviral medications cease, HIV replication resumes and again becomes detectable in the bloodstream.
In most cases, CD4 counts increase once viremia is suppressed. Once antiretroviral therapy starts, it should continue indefinitely. One very large study randomized patients to continue antiretroviral medications indefinitely, or to discontinue and restart their medications based on their CD4 counts. Patients who interrupted their treatment had higher rates of death and both HIV-related and non-HIV-related (cardiovascular, renal, and hepatic) serious adverse events.25
Opportunistic infections occur at relatively advanced levels of immune suppression, usually when CD4 cell counts fall below 200 cells/mL. Patients with evidence of advanced immune suppression should begin prophylaxis for opportunistic infections such as Pneumocystis jiroveci pneumonia, toxoplasmosis, and Mycobacterium avium infections. Prophylaxis is often the initial step in management of such patients, usually preceding the initiation of antiretroviral therapy.
Case Study: Part 3
Per hospital protocol, the ICU nurse was tested for HIV antibodies using a rapid HIV test. The test showed she was HIV negative. The occupational health nurse practitioner consulted with an infectious disease specialist who considered various factors, including the nature of the injury, the patient’s HIV status, and the nurse’s pregnancy, before recommending that she initiate antiretroviral postexposure prophylaxis. She took her first dose of antiretroviral medications within 4 hours of the needlestick exposure. She had significant nausea during the first few days of treatment. The nausea was relieved by prochlorperazine and improved over time. Confirmatory testing of the source patient revealed a positive Western blot assay for HIV and a high HIV viral load.