A Guide to Primary Care of People with HIV/AIDS - Canadian Public ...

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A Guide to Primary Care of People with HIV/AIDS Chapter 6: Metabolic Complications of Antiretroviral Therapy 2. A 33-year-old woman on stavudine (d4T) plus didanosine (ddI) plus efavirenz (EFV) presents with severe fatigue. No obvious cause for the fatigue is discovered and 1 week later she returns with even worse fatigue. Serum chemistries now are notable for a bicarbonate of 17 mmol/L. A serum lactate level is drawn and a lactate level of 6.3 mmol/L is reported from the laboratory. The patient is not taking any other medications and is not taking any herbal preparations. Question: Is the serum lactate level of 6.3 mmol/L concerning in this patient? 6 Answer: Experts have stratified serum lactate levels based on the risk of developing complications from hyperlactatemia. Those with a serum lactate level of 2.1-5.0 mmol/L are considered to have mild hyperlactatemia, those with a serum lactate level of at least 5 mmol/L have serious hyperlactatemia, and those with a lactate level at least 5 mmol/L plus a bicarbonate level less than 20 mmol/L have lactic acidosis. Accordingly, the patient’s serum lactate of 6.3 mmol/L (along with the serum bicarbonate of 17 mmol/L) is extremely concerning and suggests lactic acidosis, a potentially life-threatening problem. Question: If lactic acidosis is suspected, how should the patient be managed? Answer: Because hyperlactatemia and lactic acidosis result from NRTI-induced mitochondrial toxicity, the first step in managing this problem is to immediately discontinue ART. Although several case reports have suggested improvement in lactic acidosis by using compounds such as riboflavin, thiamine, L-carnitine, or co-enzyme Q, supportive care remains the mainstay of therapy. After discontinuing ART, regeneration of severely damaged mitochondrial typically requires prolonged periods, and recovery from lactic acidosis can take several months. Following recovery, the optimal management of subsequent antiretroviral therapy remains unclear. Preliminary reports suggest changing the NRTIs (typically replacing stavudine) can safely be performed, but should be done with expert consultation. 48 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to Primary Care of People with HIV/AIDS Chapter 7: Adherence to HIV Therapies Chapter 7: Adherence to HIV Therapies Laura W. Cheever, MD, ScM OVERVIEW ASSESSMENT INTERVENTIONS KEY POINTS SUGGESTED RESOURCES REFERENCES CASES OVERVIEW What is meant by medication adherence? Medication adherence means a patient takes the prescribed dose of prescribed medications on the prescribed schedule, following prescribed dietary instructions. Patient adherence to medical appointments and to behaviors that minimize the risk of transmission of HIV to others correlates strongly with adherence to medications and is an important part of primary care of HIV-infected patients but will not be addressed in this chapter. Why is medication adherence so important in HIV therapy? Nonadherence to prescribed therapy is a ubiquitous problem in medicine. In chronic diseases, including asthma, diabetes, and hypertension, only 50% of patients take their medication as prescribed more than 80% of the time. The same is true of patients with HIV infection. However, because of the rapid multiplication and mutation rate of HIV and the relatively low potency and short half-life of most antiretrovirals, very high levels of adherence to antiretroviral schedules are necessary to avoid viral resistance. In comparison with patients who are adherent to antiretroviral therapy (ART), nonadherent patients have: 1) Higher mortality (2.5 adjusted relative hazard) (Wood, et al, 2003), 2) Lower increase in CD4 cell count (6 cells/mm 3 increase for nonadherent patients versus 83 cells/mm 3 increase for adherent patients) (Paterson 2000), and 3) Increased hospital days (12.9 days/1000 days of followup for nonadherent patients versus 2.5 hospital days/1000 days for adherent patients) (Paterson, et al, 2000). How adherent do patients need to be to avoid viral resistance? Results of a study of adherence and response to therapy among primarily antiretroviral-experienced patients taking protease inhibitors (PIs) showed that a >95% adherence rate was necessary for 78% of patients to achieve an undetectable viral load (Paterson, 2000); however, some patients with significantly less adherence also had success (see Figure 7-1). Exactly how adherent individual patients need to be is not known and probably depends on several factors, including preexisting antiretroviral resistance, viral load, viral genetic barriers to the development of drug resistance, and drug half-life. Patients should be counseled that the risk of viral resistance increases with nonadherence and that nearly perfect adherence is the goal. Of note, patients with very low levels of adherence may be at decreased risk of developing viral resistance because there is not enough selective pressure (Bangsberg, et al, 2003). ASSESSMENT What factors impact adherence? Many factors contribute to a patient’s ability to adhere to medication schedules (Table 7-1). Note that race, education level, and income are generally not predictive of adherence. Providers must remember that factors predicting adherence or nonadherence are only associations and are not absolutely predictive. For example, although patients who use addictive substances are more likely to be nonadherent, some patients with heavy alcohol or drug use are adherent to ART. 7 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 49
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