HIV opportunistic infections and HIV treatment

1. HIV opportunistic infections and HIV treatment Sabrina Assoumou, MD Section of Infectious Diseases

2. Outline • Case 1 • HIV opportunistic infections • HIV treatment principles • HIV treatment options • Case 2

3. Case 1 • 40 y/o F admitted with • Fever, HA, and sweats for 3 weeks • Diplopia and increased somnolence for 1d • Diagnosed with HIV two months ago ( CD4 166, vl 66,923). ARVs were started immediately. • Current regimen: tenofovir, emtricitabine and efavirenz

4. Case 1 (con’t) • PE: 100.8 F • Awake but drowsy and oriented to person, but not time • L eye cannot move laterally with leftward gaze • CT scan: mildly increased ventricle size • LP: Cell count 122, gluc 62, Protein 433

5. Case 1 (con’t) Infection with which of the following is the most likely cause of this patient’s clinical presentation? • Cryptococcus neoformans • CMV • Histoplasma capsulatum • Toxoplasma gondii

6. HIV Opportunistic Infections

7. Primary OI prophylaxis • CD4 <200 • CD4 <100 • CD4 <50

8. Primary OI prophylaxis • CD4 <200: PCP • CD4 <100: Toxoplasmosis if positive serology • CD4 <50: MAI

9. Severe PCP

10. Toxoplasmosis

11. PML

12. MAI-filled macrophages in spleen

13. Thrush

14. Herpes Zoster (Shingles)

15. Cytomegalovirus Retinitis

16. HIV therapy

17. Goals of therapy • Improve quality of life • Reduce HIV-related morbidity and mortality • Restore and/or preserve immunologic function • Maximally and durably suppress HIV viral load • Prevent HIV transmission

18. HIV therapy • Who? • What? • When? • Check genotype prior to initiation

19. Initial ART Regimens: DHHS Categories • Preferred • Randomized controlled trials show optimal efficacy and durability • Favorable tolerability and toxicity profiles • Alternative • Effective but have potential disadvantages • May be the preferred regimen in individual patients • Acceptable • Less virologic efficacy, lack of efficacy data, or greater toxicities

20. Preferred regimen • 3 main categories: • 1 NNRTI + 2 NRTIs • 1 PI + 2 NRTIs • 1 II + 2 NRTIs

21. Initial Treatment: Preferred

22. ARV Components in Initial Therapy: NNRTIs ADVANTAGES Long half-lives Less metabolic toxicity (dyslipidemia, insulin resistance) than with some PIs PIs and II preserved for future use DISADVANTAGES Low genetic barrier to resistance – single mutation Cross-resistance among most NNRTIs Rash; hepatotoxicity Potential drug interactions (CYP450) Transmitted resistance to NNRTIs more common than resistance to Pis

23. ARV Components in Initial Therapy: PIs ADVANTAGES Higher genetic barrier to resistance PI resistance uncommon with failure (boosted PI) NNRTIs and II preserved for future use DISADVANTAGES Metabolic complications (fat maldistribution, dyslipidemia, insulin resistance) GI intolerance Potential for druginteractions (CYP450), especially with RTV

24. ARV Components in Initial Therapy: Raltegravir ADVANTAGES Virologic response noninferior to EFV Fewer adverse events than with EFV Fewer drug-drug interactions than with PIs or NNRTIs NNRTIs and PIs preserved for future use DISADVANTAGES Twice-daily dosing Lower genetic barrier to resistance than PIs

25. ARV-Associated Adverse Effects: Rash • Most common with NNRTIs, especially Nevirapine • Most cases mild to moderate, occurring in first 6 weeks of therapy; occasionally serious (eg, Stevens-Johnson syndrome) • PIs: especially Darunavir • NRTIs: especially abacavir (hypersensitivity syndrome) • CCR5 antagonist: Maraviroc

26. ARV-Associated Adverse Effects: Nephrotoxicity • Renal insufficiency associated with Tenofovir, Indinavir • TDF: • Cr, proteinuria, glycosuria, hypophosphatemia, hypokalemia • Indinavir: Cr, pyuria, hydronephrosis or renal atrophy • Nephrolithiasis: Indinavir, Atazanavir

27. ARV-Associated Adverse Effects: Hepatotoxicity • Severity variable: usually asymptomatic, may resolve without treatment interruption • May occur with any NNRTI or PI, most NRTIs • Nevirapine: • risk of severe hepatitis in first 18 weeks of use (monitor LFTs closely) • increased risk in chronic hepatitis B and C • women, and high CD4 count at initiation (>250 cells/µL in women, >400 cells/µL in men)

28. ARV-Associated Adverse Effects: Insulin Resistance, Diabetes • Insulin resistance, hyperglycemia, and diabetes associated with AZT, some PIs (LPV/r), especially with chronic use • Mechanism not well understood • Insulin resistance, relative insulindeficiency • Screen regularly: fasting glucose

29. ARV-Associated Adverse Effects: Hyperlipidemia •  Total cholesterol, LDL, and triglycerides • Associated with all RTV-boosted PIs, efavirenz, AZT, abacavir •  HDL seen with efavirenz, ritonavir-boosted PIs • Concern for cardiovascular events, pancreatitis • Monitor regularly • Treatment: consider ARV switch; lipid-lowering agents (caution with PI + certain statins)

30. Case 2 • 25 yo F who is 12 weeks pregnant • Found to be HIV-infected during routine pregnancy evaluation • She is asymptomatic • PE: normal. No oral thrush, LAD • CD4 865, vl 510 • Hepatitis B negative, Genotype: no resistance

31. Case 2 ( con’t) • Which of the following is the most appropriate management? • Begin ARVs at the onset of labor • Begin tenofovir, emtricitabine, and efavirenz, now • Begin AZT, lamivudine, lopinavir-ritonavir • Repeat CD4 and treat if the CD4 is <500

32. Conclusions • Remember CD4 cut offs for primary OI prophylaxis ( 200, 100, 50) • ALL HIV-infected patients should be on ARVs • Basic regimen 2NNRTI + PI or NNRTI or II