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Beyond ART: Primary care pharmacotherapy for people living with HIV
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As highly active ART options continue to grow and improve, patients being treated for HIV infection are living much longer, healthier lives. As such, primary care disease screening and management recommended for the general population must also be provided to the aging HIV population.
While many primary care decisions are identical between both populations, HIV infection and its treatment can contribute additional risk factors and side effects which, if not addressed and corrected, could lead to medication nonadherence. Additionally, highly active ART (HAART) is implicated in a number of drug-drug interactions that must be considered when choosing therapies. Selected primary care issues and the impact of HIV on care decisions are reviewed below.
Maintaining up-to-date immunizations is very important for people living with HIV, though schedules are modified for those who are severely immunocompromised. Specifically, the CDC recommends against giving the shingles vaccine to those with a CD4 count less than 200 cells/mm3. In addition, while adults who did not receive the measles-mumps-rubella (MMR) or varicella vaccines as children are generally advised to receive them as adults, these vaccines should not be given to HIV patients with CD4 counts below 200 cells/mm3. The same is true for HIV-positive children with CD4 counts less than 200 cells/mm3 at the time when MMR and varicella vaccines are typically scheduled. While yearly influenza vaccines are recommended for all HIV patients, FluMist Quadrivalent (influenza vaccine live intranasal, MedImmune) should not be used. Otherwise, all routinely recommended vaccines should be given to patients with HIV in consultation with current immunization guidelines.
Leah Molloy
As with all aging patients, reductions in bone mineral density (BMD) can increase the risk for fractures among those living with HIV, but some antiretroviral agents may further increase patient risk. Multiple studies have attempted to characterize relationships between HIV and HAART and the development of bone-related disease states such as hyperparathyroidism, vitamin D deficiency and osteopenia. Likely owing to the multifactorial nature of vitamin D depletion and the multiple drugs used in HAART regimens, results have been largely inconclusive but have identified some associations. The two antiretrovirals best recognized for involvement in osteopenia are the nucleotide reverse transcriptase inhibitor (NRTI) Viread (tenofovir, Gilead Sciences), and the non-NRTI Sustiva (efavirenz, Bristol-Myers Squibb). Tenofovir can cause elevated parathryroid horomone (PTH) concentrations by promoting renal calcium and phosphate losses, and it has additionally been associated with decreased hip BMD independent of effects on PTH. While not confirmed to translate directly to changes in PTH or BMD, efavirenz is associated with decreased concentrations of vitamin D. National primary care guidelines for HIV patients recommend bone densitometry studies for men aged 50 years and older and postmenopausal women, as well as appropriate management, including calcium and vitamin D supplementation, and bisphosphonates where indicated.
Other well-characterized metabolic complications of HIV and its treatment are insulin resistance and dyslipidemia. Independent of HAART, patients with HIV demonstrate greater rates of both lipolysis and de novo lipogenesis compounded by impaired insulin-mediated suppression of lipolysis. Upon initiating HAART, lipid panel abnormalities characterized by decreased high-density lipoprotein and increased low-density lipoprotein and triglycerides are common, likely owing to an impaired ability of adipocytes to differentiate store triglycerides caused by protease inhibitors. Additionally, altered body fat distribution is common and characteristically involves increased central and visceral fat accumulation with concomitant loss of subcutaneous fat in the face and limbs. Abnormal lipid panels and fat distribution alone can cause altered glucose metabolism, as does HIV-induced chronic inflammation. Compared with antiretroviral-naive patients, those receiving treatment are at a significantly higher risk for the development of insulin resistance and type 2 diabetes. Protease inhibitors contribute to this by inhibiting endogenous glucose transporters, and NRTI-mediated mitochondrial toxicity also is involved. Fortunately, the agents most strongly implicated such as Zerit (stavudine, Bristol-Myers Squibb), Videx (didanosine, Bristol-Myers Squibb) and Crixivan (indinavir, Merck) are used infrequently in treatment regimens today, but other involved agents like Retrovir (zidovudine, ViiV Healthcare) and some protease inhibitors are still commonly prescribed. Taken together, HIV-related dyslipidemia and insulin resistance increase cardiovascular risk and must be addressed by health care providers. Management of dyslipidemia typically involves statin treatment. However, care must be taken to avoid drug-drug interactions as protease inhibitors and Tybost (cobicistat, Gilead Sciences) inhibit metabolism and subsequently increase serum concentrations of many statins, while the opposite is true of efavirenz, which can induce statin metabolism. Pravastatin is generally free of drug-drug interactions as it is metabolized independently of the cytochrome P450 enzymes, though national guidelines also support initiation of low doses followed by careful titration of atorvastatin and Crestor (rosuvastatin, AstraZeneca). Additionally, the growth hormone-releasing analog Egrifta (tesamorelin, Theratechnologies) reduces HIV-related central adiposity without further reducing the subcutaneous fat typically lost from the face and limbs.
In the setting of greater longevity among HIV patients, primary care for common conditions must be addressed, with attention paid to nuances specific to the HIV-positive population. For more comprehensive guidance, the reader is referred to practice guidelines available through the Infectious Diseases Society of America and the New York State Department of Health AIDS Institute.
Correction:
This article erroneously reported the brand name and generic compound for a statin drug that is generally free of drug-drug interactions as it is metabolized independently of the cytochrome P450 enzymes. The proper generic compound is pravastatin sodium. The Infectious Disease News editors regret the error.
References:
Aberg JA, et al. Clin Infect Dis. 2014;doi:10.1093/cid/cit665.
Das S, et al. Recent Pat Antiinfect Drug Discov. 2014;9:6-13.
New York State Department of Health AIDS Institute. Primary care approach to the HIV-infection patient. www.hivguidelines.org/wp-content/uploads/2014/11/primary-care-approach-to-the-hiv-infected-patient.pdf. Accessed April 10, 2015.
Orkin C, et al. AIDS Rev. 2014;16:59-74.
Patel TS, et al. HIV AIDS (Auckl). 2013;doi:10.2147/HIV.S30948.
Stanley TL, et al. Clin Infect Dis. 2012;doi:10.1093/infdis/jis205.
U.S. Department of Health and Human Services. CDC. 2015 recommended immunizations for adults: by age. www.cdc.gov/vaccines/schedules/downloads/adult/adult-schedule-easy-read.pdf. Accessed April 10, 2015.
For more information:
Leah Molloy, PharmD, is a clinical pharmacist, specialist in infectious disease, at Children’s Hospital of Michigan, Detroit. She can be reached at Children’s Hospital of Michigan, Department of Pharmacy Services, 3901 Beaubien St., Detroit, MI 48201; email: lmolloy@dmc.org.
Disclosure: Molloy reports no relevant financial disclosures.