HIV Update. On The Cutting Edge A Chronic Disease. Rhett M Shirley, MD

Transcription

1 HIV Update On The Cutting Edge A Chronic Disease Rhett M Shirley, MD

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3 CDC

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6 Mid-point life expectancy estimates at age 20 years in three calendar periods, overall and by sociodemographic characteristics, Samji H et al. PLoS One. 2013;8(12):e81355.epub2013

7 Within 5 years of ART initiation, Non-AIDS related mortality surpasses AIDS related mortality Gill, G et al. Clin Infect Dis (10)1387

8 Comorbidity Distribution Cross-sectional analysis of comorbidity prevalence in prospective cohort study of HIV-infected pts (n = 540) vs controls (n = 524) 45 yrs of age P <.001 HIV-uninfected pts HIV-infected pts Pts (%) P =.018 P =.008 P =.044 Schouten J, et al. Clin Infect Dis. 2014;59:

9 The Facts About Aging With HIV People living with HIV now have life expectancies that are very close to that of people without HIV But people with HIV have a greater risk for conditions that are associated with getting older The reasons why HIV-positive people suffer more from these conditions are debated, but all agree that lifestyle plays a role Although aging with HIV is inevitable, the course of aging can be influenced by actions eg, healthy diet, exercise

10 Interplay of Age With Morbidity HIV infection Lifestyle Antiviral treatment Aging Risk of comorbidities increases as individuals get older HIV does not cause these illnesses However, HIV and/or ART may increase the risk

11 DHHS: Key Considerations When Caring for Older HIV-Infected Pts DHHS has included older adult pts as a separate special population with the following recommendations: ART is recommended in all pts, regardless of CD4+ cell count, but is especially important in older pts ART-associated AEs may occur: monitor bone, kidney, metabolic, CV, and liver health Increased risk of drug drug interactions between ARV drugs and other medications HIV experts and primary care providers should work together to manage complex comorbidities DHHS Guidelines. July 2016.

12 DHHS Considerations for Initial ART Based on Age-Related Comorbidity Scenario DHHS Guidelines CKD (egfr < 60 ml/min) Consider Avoiding TDF, especially in RTVcontaining regimens ART-Specific Consideration Options TAF (if egfr > 30 ml/min) ABC/3TC (if HLA-B*5701 negative; if HIV-1 RNA > 100,000 c/ml, do not use with EFV or ATV/RTV; 3TC dose adjustment if CrCl < 50 ml/min) DRV/RTV + RAL (if HIV-1 RNA < 100,000 c/ml and CD4+ cell count > 200 cells/mm 3 ) LPV/RTV + 3TC (3TC dose adjustment if CrCl < 50 ml/min) Osteoporosis TDF TAF ABC/3TC (if HLA-B*5701 negative; if HIV-1 RNA > 100,000 c/ml, do not use with EFV or ATV/RTV) CVD Hyperlipidemia ABC LPV/RTV PI/RTV or PI/COBI EFV EVG/COBI DTG RAL

13 ART and Effects on Lipids TDF /TAF RAL DTG RPV ABC EFV ATV/RTV or ATV/COBI DRV/RTV or DRV/COBI EVG/COBI

14 Drug Drug Interactions With ART and Diabetes and Lipid-Lowering Therapy Antiretroviral Contraindicated Titrate Dose No Dose Adjustment RPV [1] Atorvastatin Pitavastatin 1DHHS Guidelines EVG/COBI/FTC/ TDF [1] DTG [1,2] ATV/RTV [1] DRV/RTV [1] EFV [1] RAL [1] ATV/COBI or DRV/COBI Lovastatin Simvastatin Lovastatin Simvastatin Lovastatin Simvastatin Lovastatin Simvastatin Atorvastatin Rosuvastatin Metformin Atorvastatin Rosuvastatin Atorvastatin Pravastatin Rosuvastatin Atorvastatin Simvastatin Pravastatin Rosuvastatin Pitavastatin Pitavastatin Pitavastatin

15 Drugs for Common Conditions in the Aging That May Interact With ART Comorbidity Interacting ARVs Comorbidity Drugs T2DM Metformin DTG/3TC/ABC, DTG + FTC/TDF or FTC/TAF, EVG/COBI/FTC/TDF, EVG/COBI/FTC/TAF GERD CVD COPD Antacid PPI Statin, Antiarrhythmic Beta-agonist Glucocorticoid All ATV/RTV + FTC/TDF or FTC/TAF, DRV/RTV + FTC/TDF or FTC/TAF, RPV + FTC/TDF or FTC/TAF EVG/COBI/FTC/TDF, EVG/COBI/FTC/TAF, ATV/RTV + FTC/TDF or FTC/TAF, DTG/3TC/ABC EVG/COBI/FTC/TDF, EVG/COBI/FTC/TAF ATV/RTV + FTC/TDF or FTC/TAF, DRV/RTV + FTC/TDF or FTC/TAF DHHS Guidelines

16 Drug Drug Interactions With ART and CVD and Antihypertensive Therapy Antiretroviral Contraindicated Titrate Dose ARV/RTV or DRV/RTV Dabigatran* Amlodipine, diltiazem, felodipine, lacidipine, nicardipine, nifedipine, nisoldipine, indapamide, doxazosin, amlodipine, diltiazem, verapamil, warfarin EFV EVG/COBI Dabigatran* Lercanidipine, amlodipine, diltiazem, felodipine, lacidipine, nicardipine, nifedipine, nisoldipine, verapamil indapamide, doxazosin Amlodipine, diltiazem, felodipine, lacidipine, nicardipine, nifedipine, nisoldipine, indapamide, doxazosin, amlodipine, diltiazem, verapamil, warfarin DHHS Guidelines EACS Guidelines DTG, RAL, ABC, FTC, 3TC, and TDF have no significant interactions. *If CrCl < 50 ml/min.

17 ART Considerations for Pts With Cardiovascular Complications DHHS considerations Consider avoiding ABC, LPV/RTV Drug drug interactions occur between calcium channel blockers and ART components

18 Fracture Prevalence Is Increased in Older HIV- Positive Pts 8525 HIV-infected pts compared with 2,208,792 uninfected pts in Partners HealthCare System HIV Non-HIV Women Men HIV Non-HIV Fracture Prevalence/ 100 Persons P =.002 (overall comparison) Fracture Prevalence/ 100 Persons P <.0001 (overall comparison) Age (Yrs) Age (Yrs) Triant V, et al. J Clin Endocrinol Metab. 2008;93:

19 TAF vs TDF + EVG/COBI/FTC: Changes in BMD Mean % Change From Baseline (SD) Spine EVG/COBI/FTC/TAF EVG/COBI/FTC/TDF P < Hip P < Pts at Risk, n E/C/F/TAF E/C/F/TDF TAF treatment was associated with smaller BMD loss than TDF treatment Sax P, et al. Lancet. 2015;385: Wk Wk

20 ART Considerations for Pts With Bone Complications DHHS considerations: Consider avoiding TDF: associated with greater decrease in BMD along with renal tubulopathy, urine phosphate wasting, and osteomalacia Consider ABC/3TC Significantly greater BMD loss with PI-based regimens vs RAL-based regimens DTG + ABC/3TC associated with less bone turnover than EFV/TDF/FTC

21 PrEP (HIV PreExposure Prophylaxis) Who is eligible: High risk of HIV acquisition Committed to medication adherence Patients must be screened for conditions that would result in adverse effects of PrEP HIV HBV. Test and vaccinate if indicated. Renal dysfunction (egfr < 60 ml/min) Osteoporosis (consider DXA scan for those at high risk)

22 PrEP Patients must understand that antiretroviral preexposure prophylaxis is not Levitra and not a morning after pill TDF/FTC: Truvada must be taken daily Time to effectiveness may be delayed for 1-3 weeks after initiation Patients must be committed to routine laboratory monitoring Screen for HIV every 3-6 months Follow for medication toxicity q3-6 months: creatinine, urinalysis with microalbumin Patients must be reminded that antiretroviral therapy prophylaxis does NOT prevent syphilis, gonorrhea, chlamydia, genital warts, viral hepatitis, HSV, Most private and public insurers cover TDF/FTC for this purpose but copays vary widely

23 Kaplan- Meier estimates of time to HIV infection Grant et al. N Engl J Med 2010; 363:

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25 Partners PrEP Study 82 infections detected after randomization. 30 of those were in the prophylaxis group The detection of tenofovir was associated with 85% RRR in HIV acquisition Baeten et al. N Engl J Med. 2012; 367:

26 PROUD: Pre-exposure Prophylaxis to Prevent The Acquisition of HIV-1 Infection Randomized Open Label Trial of MSM in England. Real World Patient #1: perhaps infected at enrollment Patient #2: Had not been prescribed study drug since enrollment Patient #3: Had not had clinic attendance in 41 weeks at the time of HIV diagnosis

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