Pharm III - HIV medicine Case study
A 35-year-old woman with HIV infection who is treatment-naïve presents to clinic to discuss initiation of ART. Her baseline viral load is 84,000 copies/mL and her CD4+ count is 325 cells/mm3. You would like to avoid a PI-based regimen because of a history of hyperlipidemia and hyperglycemia; the physician also would like to avoid efavirenz because the patient is of childbearing potential. You are somewhat concerned about adherence because the patient has had trouble adhering to her diabetes medications. You decide that you would like to start her on an INSTI-based regimen. Her current medications include fluticasone/salmeterol inhaler, albuterol inhaler, metformin, and glipizide. Testing has been performed and HLAB*5701 is present. Which one of the following is best to recommend for this patient? Emtricitabine/tenofovir plus dolutegravir 50 mg daily. Emtricitabine/tenofovir plus raltegravir 400 mg twice daily. Dolutegravir/abacavir/lamivudine daily. Elvitegravir/cobicistat/emtricitabine/tenofovir daily.
A A once-daily regimen would be preferred if using an INSTI-based regimen in a patient in whom adherence may be a concern. The correct dose for dolutegravir in treatment-naïve patients is 50 mg daily. Dolutegravir likely has the highest barrier to resistance compared with the other integrase inhibitors and provides a oncedaily option. Because of the presence of HLAB*5701, abacavir cannot be used (Answer A is correct; Answer C is incorrect). Raltegravir has a lower barrier to resistance and is twice daily (Answer B is incorrect). Elvitegravir/cobicistat/emtricitabine/tenofovir should be avoided due to the drug interaction with salmeterol/fluticasone (Answer D is incorrect).
A 62-year-old man with HIV infection and a CD4+ count of 150 cells/mm3 is attending his regular 3-month visit with his primary care provider. His viral load has been suppressed for the past 3 years without any significant change in his CD4+ count. During a review of his immunization record, you note that his last pneumococcal vaccine was 5 years ago when he received pneumococcal polysaccharide vaccine 23-valent (PPV23). Which one of the following is best to recommend for this patient? Administer a pneumococcal conjugate vaccine with the most common variant containing antigens to 13 different serotypes (PCV13) now and repeat PPV23 in 2 months Administer PCV13 now Administer PPV23 because it has been more than 5 years since last immunization Defer PCV13 administration until the CD4+ count is greater than 200 cells/mm3
A According to the latest CDC and ACIP recommendations, administration of PCV13 first, followed by PPV23, would be the preferred option (Answer A is correct; Answer B and Answer C are incorrect). Any immunocompromising condition including HIV is an indication for pneumococcal vaccination and is not dependent on age. Although a seroprotective antibody response will be greater with a higher CD4+ count, it is not appropriate to defer vaccination, hoping that the count will increase (Answer D is incorrect). Withholding the vaccine because of poor efficacy is not recommended because this patient may still have a protective response. Because PCV13 is not a live, attenuated vaccine, it may be administered regardless of CD4+ count with respect to patient safety.
Which is the best parameter to monitor if F.G. is to receive abacavir? Peripheral neuropathy Presence of HLA-B*5701 Endocrine disturbances such as hyperglycemia, fat redistribution, and lipid abnormalities Hyperbilirubinemia
B A patient taking abacavir should be screened for the presence of the HLA-B*5701 allele. If the patient is positive for this allele, the risk of hypersensitivity reactions is increased (Answer B is correct). Because abacavir does not cause peripheral neuropathy (although didanosine, zalcitabine, and stavudine do), this does not need to be monitored (Answer A is incorrect). Endocrine disturbances (e.g., hyperglycemia, fat redistribution, lipid abnormalities) are more associated with PIs (Answer C is incorrect). Abacavir does not cause hyperbilirubinemia; therefore, the patient need not be monitored for this (although a patient taking atazanavir does) (Answer D is incorrect).
A 32-year-old man returns to clinic for follow up on his ART regimen of efavirenz/emtricitabine/tenofovir which he has been taking for 1 year. His last HIV viral load (1 month ago) was less than 50 copies/mL and his CD4+ count was 465 cells/mm3. The patient also has active hepatitis B infection. He reports he really likes the one pill once-daily option that his current regimen provides, but he is having abnormal dreams that are bothersome and sometimes cause difficulty sleeping. He has not missed any doses since starting his ARV regimen. He wants to know if there are any other options for switching his ART regimen. The patient has a history of depression that is well controlled on fluoxetine 40 mg daily and anxiety well controlled on alprazolam 0.5 mg twice daily as needed. Which one of the following ART regimens is best to recommend for this patient? Elvitegravir/cobicistat/emtricitabine/tenofovir. Dolutegravir/abacavir/lamivudine. Rilpivirine/emtricitabine/tenofovir. Continue on his current ARV regimen.
B Amphotericin should be avoided because the patient experienced renal dysfunction while receiving it. Also, this would be a subtherapeutic dose (Answer A is incorrect). Fluconazole would be inappropriate because it does not have activity against Aspergillus (Answer C is incorrect). Voriconazole should be dosed 200 mg orally twice daily and levels monitored since the patient is receiving protease inhibitors. Voriconazole 400 mg orally daily is an inappropriate dose (Answer D incorrect). Posaconazole may be used in the management of aspergillosis and should also be closely monitored in the presence of protease inhibitors (Answer B is correct).
A 26-year-old woman is contemplating trying to become pregnant. Her partner, who has HIV infection, is currently being treated with highly active antiretroviral therapy (HAART). Testing for HIV determines that the patient is seronegative. Which one of the following would be best to recommend to this patient for periconception preexposure prophylaxis to reduce HIV transmission? Zidovudine Tenofovir/emtricitabine Nevirapine Zidovudine/lamivudine/lopinavir with ritonavir
B Periconception preexposure prophylaxis (PrEP) is a newer concept being studied, predominantly in Africa, to provide an additional option to minimize the risk of HIV transmission in couples in which one partner is seropositive and the other is seronegative. The goal behind PrEP is to maintain blood and genital levels of antiretroviral drugs sufficient to prevent HIV transmission. The TDF2 study is a placebo-controlled trial of PrEP designed to minimize HIV transmission in adults 18-39 years of age in Botswana. The PrEP consisted of daily use of tenofovir with emtricitabine. The study's results indicate a reduction in HIV acquisition by the uninfected partner by 63% (95% CI, 21.5-83.4). Effectiveness was noted in both sexes. A second study, the Partners PrEP Study, was conducted in Kenya and Uganda and was a three-armed, placebo-controlled trial examining daily use of tenofovir or tenofovir plus emtricitabine. Once again, successful inhibition of HIV transmission was noted compared with placebo. Single-drug therapy with tenofovir resulted in 62% less HIV infections (95% CI, 34-78), whereas combined therapy noted a 73% reduction in infectivity (95% CI, 49-85) (Answer B is correct; Answer A, Answer C, and Answer D are incorrect). The use of daily oral PrEP during pregnancy offers new potential for the prevention of HIV transmission in discordant couples. However, the current studies are not conclusive, and further studies are planned. Future studies that also examine the adverse effects, including congenital anomalies, of this concept are needed.
A 34-year-old man asks about "a pill you can take to prevent HIV." The patient is a man who has sex with men and reports he is not in a relationship. He says he understands the importance of using protection during intercourse but does have multiple sexual partners. He last had an HIV test 3 months ago; the test was negative. He does not currently take any other medications. The patient asks if he can receive pre-exposure prophylaxis (PrEP). Which one of the following is the best answer to give this patient? No, PrEP is only indicated for heterosexual serodiscordant couples. Yes, he is an excellent candidate for PrEP and he can start right away. Yes, but he must get a more recent HIV test before starting PrEP. Yes, he should take PrEP only before he has a sexual encounter.
C The patient is a good candidate for PrEP as long as he receives additional risk-reduction counseling, counseling on adherence, and education on the importance of taking the medication every day. The patient must have an HIV negative test immediately before starting PrEP (Answer B is incorrect; Answer C is correct). PrEP is approved for both homosexual and heterosexual patients (Answer A is incorrect). PrEP must be taken every day to be most effective (Answer D is incorrect).
Six months after F.G. (from previous question) starts appropriate therapy, his CD4 count is 720 cells/mm3 , and his viral load is undetectable. Two years later, his CD4 count decreases to 310 cells/mm3 , and his viral load is 15,000 copies/mL. Resistance testing detects resistance to raltegravir. Which change is best for F.G.'s therapy? Stress adherence and continue the same regimen Change raltegravir to efavirenz Change tenofovir and emtricitabine to abacavir and lamivudine Change the entire regimen to abacavir, lamivudine, and darunavir/ritonavir
D A change in potent combination ART should be made when the viral load becomes detectable after a period of levels below detection. Some clinicians would wait and monitor the patient closely if the viral load increased to 10,000 copies/mL. However, these patients generally will need changes in therapy in the future. Testing shows resistance to raltegravir. Therefore, changes in ART must be made. Simply stressing adherence and continuing the same regimen is inappropriate (Answer A is incorrect). Ideally, a new regimen should contain at least two and preferably three fully active drugs (Answer C is incorrect). In general, changing a single antiretroviral in a failing regimen is not recommended because of the risk of rapid development of resistance (Answer B is incorrect). Changing only one drug in a regimen should be done only for intolerance. Therefore, initiating an entirely new regimen of abacavir, lamivudine, and darunavir/ ritonavir is best because changing all three agents simultaneously limits the possibility of resistance to the new regimen occurring quickly (Answer D is correct).
A 22-year-old woman with a history of HIV is seen in the high-risk obstetrics clinic. She has taken several agents for the treatment of her disease during this gestation. Her current regimen consists of emtricitabine, efavirenz, and tenofovir. Which one of the following antiretroviral agents would be best to recommend to avoid harm to the mother or fetus? Emtricitabine Efavirenz Tenofovir Zidovudine
D Little is known of the potential risks of many antiretrovirals in pregnancy. This is because of a lack of experience with the use of many of these drugs in this situation. Of the agents this patient is currently receiving, efavirenz used during pregnancy is the most controversial. Efavirenz has been associated with an increased risk of anencephaly, microphthalmia, cleft palate, and neural tube defects (NTDs) in animal models. It is considered FDA category D (Answer B is incorrect). Emtricitabine and tenofovir have been used in pregnancy. Both are considered FDA class B. Although emtricitabine has not been associated with any specific anomalies, the use of tenofovir does have the risk of effecting bone ossification in the neonate (Answer A and Answer C are incorrect). Zidovudine has been one of the most frequently chosen drugs for the management of HIV in pregnancy and for the prevention of MTCT of the virus. It is recommended to be given to the neonate after delivery to further reduce the risk of viral transmission (Answer D is correct).
You are seeing a treatment-naïve patient in clinic would like to start them on a new ART regimen. The patient is taking rivaroxaban, a CYP3A substrate, for atrial fibrillation. Which one of the following is best to recommend for this patient? Darunavir plus ritonavir plus emtricitabine/tenofovir. Elvitegravir/cobicistat/emtricitabine/tenofovir. Etravirine plus emtricitabine/tenofovir. Rilpivirine/emtricitabine/tenofovir.
D Rilpivirine is not a potent inducer or inhibitor of CYP3A; therefore, a rilpivirine-based regimen would be a good choice in this patient (Answer D is correct). Ritonavir is a potent CYP3A inhibitor and may increase bleeding risk with rivaroxaban (Answer A is incorrect). Cobicistat is also a potent CYP3A inhibitor (Answer B is incorrect). Etravirine is a CYP3A inducer and may potentially causing subtherapeutic levels of rivaroxaban (Answer C is incorrect).
F.G. is a 27-year-old man who is HIV positive but asymptomatic. His CD4 count is 550 cells/mm3 , and his viral load is 5000 copies/mL by reverse transcriptase polymerase chain reaction. Which is the best treatment for F.G.? ART should not be given because his CD4 count is still above 500 cells/mm3 Initiate emtricitabine/tenofovir only because his CD4 count is still above 500 cells/mm3 Initiate combination therapy of abacavir, lamivudine, and atazanavir/ritonavir Initiate combination therapy of tenofovir, emtricitabine, and raltegravir
D The patient should be treated at this time; a potent combination ART should be initiated in all HIV-infected patients, regardless of CD4 count (Answer A is incorrect). Combination therapy of tenofovir, emtricitabine, and raltegravir is a recommended initial therapeutic regimen (Answer D is correct). Regimens without an NNRTI, PI, or INSTI are not indicated for HIV (Answer B is incorrect). The regimen of abacavir, lamivudine, and atazanavir/ritonavir is not a recommended or alternative option. It should only be used if recommended or alternative options are not appropriate and should definitely not be first-line therapy (Answer C is incorrect).