Appropriate treatment of patients with HIV requires consideration of antiretroviral therapy and consideration of the medical, social, medication history (including alternative and herbal supplements) along with a thorough physical examination. Assessment of the patient’s knowledge of HIV, understanding of the course of disease, emotional well-being, and presence or absence of support systems is as important as a discussion of safer sex practices and contraception. Notification of sex partners is vital; the laws regarding partner notification vary from state to state. Identification of a durable power of attorney and discussion of advanced directives are valuable early in the course of the disease.
Preventive care is essential to treating patients with HIV. Some infections can be minimized by avoiding uncooked and undercooked foods such as seafood, eggs, and meats; abstaining from drinking lake and river water; avoiding contact with cat litter boxes and animals with diarrhea; and careful hand washing. Other preventive measures are appropriate vaccinations, medications for the prevention of opportunistic infections, and preexposure prophylaxis for individuals without HIV.
Vaccinations
The patient’s vaccination history should be carefully reviewed. All patients should receive the pneumococcal vaccine with an initial dose of PCV13 (Prevnar 13) with a subsequent dose of PPV23 (Pneumovax) at least 8 weeks after the initial PCV13.21 A second dose of PPV23 is recommended 5 years after the initial dose. Yearly influenza vaccination is recommended as is hepatitis B vaccination if the patient is seronegative. Hepatitis A vaccination is recommended for all susceptible men who have sex with men in addition to other susceptible individuals, and it should be considered in all patients with HIV infection. Tetanus boosters are indicated every 10 years.21
Other vaccinations such as the oral polio vaccine are contraindicated, but the inactivated polio vaccine should be given if indicated (patients traveling to endemic areas). Varicella vaccination is considered in select settings, particularly in patients with CD4 counts ≥200 cells/mm3 who are not immune to varicella. The safety of vaccination against herpes zoster is unknown but vaccination can be considered in patients >60 years old with CD4 counts ≥200 cells/mm3.21
Prophylaxis
Patients with advanced HIV disease require prophylaxis to prevent opportunistic infections. If the CD4+ count is <200 cells/mm3 (or CD4+ percentage <14%), prophylaxis against P jiroveci pneumonia should be initiated. The first-line agent is trimethoprim-sulfamethoxazole (TMP-SMX), commonly 1 double-strength tablet daily. Dapsone, 100 mg/day, is recommended for patients who are TMP-SMX intolerant and not G6PD-deficient. If the CD4+ count is <100 cells/mm3, patients with positive T. gondii IgG serologies require prophylaxis to prevent reactivation. Daily double-strength TMP-SMX is again the drug of choice. Patients receiving dapsone require the addition of weekly pyrimethamine. Although Mycobacterium avium complex prophylaxis is recommended at CD4+ counts <50 cells/mm3, initiation is never emergent. Active Mycobacterium avium complex disease should be ruled out before starting prophylaxis if the patient has any suggestive symptoms. The most common regimen is azithromycin, 1200 mg/week.
More detailed information can be obtained from the CDC and Infectious Disease Society of America guidelines for the prevention of opportunistic infections.22
Highly active antiretroviral therapy (HAART) is the mainstay of HIV treatment; however, selection of HAART has become increasingly complex and recommendations are constantly changing as new classes and agents become available. Antiretorviral resistance limits future HAART options. Thus, it is recommended that the selection of HAART be left to a clinician who has experience and specializes in managing HIV infection.
The Department of Health and Human Services (DHHS) updated their HAART treatment guidelines in April 2015. They now recommend highly active antiretroviral therapy for all HIV-infected patients to reduce disease progression and to prevent transmission to noninfected individuals. Highly active antiretroviral therapy is indicated at all CD4 cell counts.20
There are currently more than 25 drugs in six classes that are FDA approved to treat HIV infection.20 Classes of medications include nucleoside/nucleotide reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, a fusion inhibitor, a CCR5 antagonist, and integrase strand transfer inhibitors. There are also two drugs classified as pharmacokinetic enhancers that are used to improve the pharmacokinetics of the protease inhibitors and one of the integrase strand transfer inhibitors (elvitegravir).
Current recommended therapy for a treatment-naïve individual consists of a backbone of two nucleoside reverse transcriptase inhibitors in combination with a third drug from one of the following classes: an integrase strand transfer inhibitor, a nonnucleoside reverse transcriptase inhibitor, or a protease inhibitor with a pharmacokinetic enhancer (cobicistat or ritonavir)20 as outlined in Table 4.
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CrCl = creatinine clearance. |
Reprinted from US Department of Health and Human Services.20
Several alternative regimens are also available and are outlined in the DHHS guidelines. In some instances, these regimens may be preferred when taking into consideration additional factors including patient characteristics (pretreatment HIV RNA level, CD4 count, drug resistance testing results, HLA-B*5701 status), medical comorbidities, and regimen-specific constraints including adverse drug effects, interactions with other medications, convenience, and cost.20
Once HAART is initiated, the goals of HAART are to reduce HIV-associated morbidity and prolong survival, restore immune function, suppress HIV viral load, and prevent HIV transmission. The suppression of HIV-1 RNA to below the limits of assay detections usually occurs within the first 12 to 24 weeks of therapy.20
The most critical and modifiable factor affecting success is patient adherence. Only 45% of patients taking 90% to 94.9% of the prescribed doses of antiretroviral medications will achieve viral suppression (<400 copies/mL) compared with 78% of patients taking ≥95% of doses.23 Incomplete viral suppression leads to the development of drug resistance. Adherence to the antiviral regimen should be addressed at every visit in a detailed fashion, and the importance of careful adherence should be stressed. Once-daily dosing of many treatment regimens is now possible and changes in pill formulations have allowed more potent regimens to be prescribed with fewer total pills. Both pill burden and dosing frequency have been shown to correlate with adherence.
While the new HAART regimens are largely well tolerated by patients, there can be significant side effects that can be either class specific or individual to the medication itself. Side effects include hepatotoxicity, hyperglycemia, hyperlipidemia, lipodystrophy, lactic acidosis, skin rash, and effects on bones including osteonecrosis, osteoporosis, and osteopenia.24 There are also significant drug-drug interactions that can occur between antiretroviral agents and commonly prescribed medications that can lead to drug toxicities or reduction in levels of the drug or the antiretroviral agent rendering them ineffective. For a complete list of adverse effects, toxicities, and medication interactions, refer to the DHHS Antiretroviral Guidelines.20
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