presentación de powerpointregist2.virology-education.com/2017/healthyliving/05_parades.pdf ·...
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CLINICAL CASE COMORBIDITIES IN PLHIVRoger Paredes, MD, PhDInfectious Diseases Unit, irsiCaixa AIDS Research InstituteHospital Universitari Germans Trias i PujolBadalona, Catalonia, Spain
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Roberto• Male, 64 years-old• Professor of History in the University of Barcelona• Born in Buenos Aires, lives in downtown Barcelona with his male
partner • They have been together for more than 20 years, but in an open
relationship • Frequent travel to South East Asia, but last trip 2 years ago• Smokes 15 cigarretes/day since he was 14-years old up to 25/day
during exams. 2 unsuccessful attempts to quit, last one 10 years ago• Occasionally, Malt whiskey after lunch
• Admitted to our hospital’s emergency department for severe pain and functional impotence in the left lower extremity after an accidental fall while we was walking down Passeig de Gràcia
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Clinical exam
• What is the most likely diagnosis?1. Left knee fracture2. Left hip fracture 3. Left ankle fracture4. Left mid tibial fracture5. Come on… he’s just pretending
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Clinical exam• X-Ray: left transcervical femoral neck fracture
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Risk factors • Decreased bone density• Decreased muscle mass• Sex: 70% in women• Fall: Any reason witch can make you fall• Medications: cortisone• Nutrition: low calcium & vitamin D • Eating disorders like anorexia and bulimia• Age: 90% in > 70 years old• Alcohol and tobacco• Endocrine disorders • Low physical activity• Stroke & Parkinson’s disease
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Admitted to trauma• X-Ray: left transcervical femoral neck fracture
Admitted to traumaSurgical
repairment
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In trauma• Favorable surgical evolution • During hospital admission, a first-year resident notes the
following lesions in the left arm and mouth:
• A skin biopsy confirms Kaposi’s Sarcoma
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In trauma• HIV-1 Serology +• HIV-1 RNA: 125.000 copies/mL• CD4+ T-cell counts: 214 cells/mm3 (14%)• HLA B57*01: negative• Genotype (Sanger): Wildtype
• HAV +, HBV neg, HCV neg• RPR + 1/64, FTA+
• Normal TG, Cholesterol • Total: 250 mg/dL, • LDL: 140 mg/dL• HDL: 40 mg/dL
• Body TC: Normal
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Treatment Considerations for KSTumor Characteristics HIV Status Treatment Recommendations*
Minimal, nonprogressive mucocutaneous disease
Viral load undetectable Consider local interventions including radiation therapyConsider interferon or enrollment in clinical trial
Viral load detectable
Maximize antiretroviral therapyConsider local interventionsConsider interferonConsider enrollment in clinical trial
Extensive mucocutaneous without edema or KS-related symptoms
Viral load undetectable Interferon; consider chemotherapyConsider enrollment in clinical trial
Viral load detectable Maximize antiretroviral therapyConsider interferon, cytotoxic chemotherapy, or enrollment in clinical trial
Symptomatic mucocutaneous disease Any viral load Cytotoxic chemotherapy
Symptomatic visceral disease or pulmonary disease Any viral load Cytotoxic chemotherapy
Refractory disease or severe comorbid conditions Any viral load Consider local interventions for palliation
Consider chemotherapy or enrollment in clinical trial
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Treatment Considerations for KSTumor Characteristics HIV Status Treatment Recommendations*
Minimal, nonprogressive mucocutaneous disease
Viral load undetectable Consider local interventions including radiation therapyConsider interferon or enrollment in clinical trial
Viral load detectable
Maximize antiretroviral therapyConsider local interventionsConsider interferonConsider enrollment in clinical trial
Extensive mucocutaneous without edema or KS-related symptoms
Viral load undetectable Interferon; consider chemotherapyConsider enrollment in clinical trial
Viral load detectable Maximize antiretroviral therapyConsider interferon, cytotoxic chemotherapy, or enrollment in clinical trial
Symptomatic mucocutaneous disease Any viral load Cytotoxic chemotherapy
Symptomatic visceral disease or pulmonary disease Any viral load Cytotoxic chemotherapy
Refractory disease or severe comorbid conditions Any viral load Consider local interventions for palliation
Consider chemotherapy or enrollment in clinical trial
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ART initiation: START trial
INSIGHT-START Study Group NEJM 2015
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ELV/cobi/TDF/FTC• During the following 6 months
• Fast HIV-1 RNA decline to <50 c/mL• CD4+ counts increase to >350 cells/mm3• KS lesions resolve• Rehab & physiotherapy OK
• NSAIDS for leg pain• Back home• Back to classes • Walks with a cane• Smokes 20 cig/day
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NSAIDs & Antiacids• Complains of epigastric pain and still needs NSAIDs.
What can you do?
1. Give him omeprazol with no changes in his ART regimen2. Give him omeprazol minimum 2h after or 6h before his ART3. Give him antacids with no changes in his ART regimen4. Change his ART to DRVr+TDF/FTC and then hive him
omeprazol5. Tell him to be tough and stop moaning
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Accelerated aging• He gets better, 2 year follow-up
• VL still <50 c/mL, CD4+ counts 550 cells/mm3, • However, Total Cholest = 220 mg/dL, LDLc =110 mg/dL, HDLc = 50 mg/dL• Smokes 10-15 cig/day. • C-Reactive Protein 35 IU• BMI index 29
• What single medical intervention will have the greatest impact on his life expectancy?
1. Intensify diet and start on statins2. Initiate ACE Antagonists3. Quit smoking4. Treat him with sevelamer5. Modify his microbiome
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Smoking kills
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Smoking kills
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Smoking kills• Smoking cessation by 10%–25% of HIV-infected smokers
could save approximately 106 000–265 000 years of life.
• HIV-infected US smokers aged 40 years lose >6 years of life expectancy from smoking, possibly outweighing the loss from HIV infection itself.
• Smoking cessation should become a priority in HIV treatment programs.
Reddy, JID 2016
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Lipids• He quits smoking!!!!!
• However, Total Cholest = 234 mg/dL, LDLc =124 mg/dL, HDLc = 48 mg/dL• BMI index 29 32• Develops criteria for type 2 diabetes
• In addition to diet and exercise, which statin would be preferable if you keep him on the same ART?
1. Simvastatin2. Atorvastatin3. Pravastatin4. Rosuvastatin5. If he is switched to DTG, he could receive Simvastatin6. 4 and 5
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Liverpool HIV Interactions• Coadministration between atorvastatin and elvitegravir/cobicistat (150/150 mg once daily) has not been studied.
Atorvastatin is metabolized by CYP3A4. Coadministration with elvitegravir/cobicistat could potentially increase atorvastatin concentrations. If the use of atorvastatin is considered strictly necessary, start with the lowest dose of atorvastatin and titrate carefully while monitoring for safety. Emtricitabine and tenofovir-DF do not interact with this metabolic pathway.
• Coadministration of rosuvastatin (10 mg single dose) and elvitegravir/cobicistat (150/150 mg once daily) decreased elvitegravir Cmax and Cmin by 6% and 2%, and increased AUC by 2% (n=10). Rosuvastatin AUC and Cmax increased by 38% and 89%, respectively. The increase in rosuvastatin exposure is transient and not considered clinically relevant. Dose modifications are not necessary when rosuvastatin is administered in combination with Stribild.
• Coadministration of simvastatin and DTG has not been studied but based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Simvastatin is metabolized by CYP3A4, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.
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Diabetes• After 6 months on
Rosuvastatin• Total Cholest = 201 mg/dL,
LDLc =101 mg/dL, HDLc = 53 mg/dL
• BMI index 32• Begins metformin up to 850
mg BID
• Which of these ARVs interacts with metformin?1. Elvitegravir2. Cobicistat3. TDF4. Dolutegravir5. Darunavir/r
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Diabetes Cobicistat
Dolutegravir
• Increased metformin Cmax and AUC
• DTG QD: 66% and 79%, • DTG BID: 111% and 145%.
• US Prescribing Information suggests total daily dose of metformin to 1000 mg.
• Monitoring renal function and blood glucose
• Increased risk for lactic acidosis in moderate renal impairment
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Fracture prevention• Improvement in HbA1c <6.5• No adverse events…. But still on TDF! • DEXA scan: T-score -2.7
• Which of these ART interventions would help prevent further fractures?
1. Switch to TAF/FTC/ELV/cobi 2. Switch to ABC/3TC/DTG3. Switch to boosted-PI monotherapy4. Stop ART
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TDF to ABC switch
Negredo JAC 2014
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TDF to TAF switch
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TAF does not impact lipids
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Reducing risk of fractures
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Learning points• Early ART is key• Smoking is central to accelerated aging and survival
reductions in PLHIV • Beware interactions
• Statins & ritonavir but also cobicistat Sinvastatin is OK if DTG• Metformin with DTG, but also cobicistat (uncertain clinical
significance)• Prevention of bone mineral loss may involve switch from
TDF to ABC or TAF no direct comparisons• TAF does not impact lipids • Need for comprehensive geriatric management