AIDS treatment guidelines

1. HAART
By : Ankit Gupta
JR II
General Medicine Deptt.

2. Structure of HIV

3. Reverse
Transcriptase Integrase
Fusion
ProteaseViral DNA
LIFE CYCLE OF HIV

4. Primary Goals of ART
• Reduce HIV-related morbidity and prolong survival
• Improve quality of life
• Restore and preserve immunologic function
• Maximally and durably suppress viral load
• Prevent vertical HIV transmission

5. Classification of Antiretroviral Drugs
• Five types of antiretroviral drugs
• Inhibit enzymes required for HIV
– Reverse transcriptase inhibitors
– Integrase inhibitors
– Protease inhibitors
• Block viral entry into cells
– Fusion inhibitors
– CCR5 antagonists

6. Reverse Transcriptase
Inhibitors
NRTI’s
Abacavir (ABC)
Didanosine (ddI)
Emtricitabine (FTC)
Lamivudine (3TC)
Stavudine (d4T)
Zidovudine (AZT)
NtRTI’s
Tenofovir (TDF)
NNRTI’s
Efavirenz (EFV)
Etravirine (ETV)
Nevirapine (NVP)

7. Drugs Common Side effects
Zidovudine &
Stavudine
Myopathy, lactic acidosis, hepatic steatosis, nail pigmentation
,lipoatrophy, hyperglycemia
Didanosine Pancreatitis, peripheral neuropathy, lactic acidosis hepatomegaly
with steatosis, optic neuritis ,hyperglycemia
Zalcitabine Peripheral neuropathy, pancreatitis, lactic acidosis, hepatomegaly
with steatosis, oral ulcers
Lamivudine Flare of hepatitis in HBV-coinfected patients who discontinue drug
Emtricitabine Hepatotoxicity in HBV-coinfected patients who discontinue drug,
skin discoloration
Abacavir Hypersensitivity reaction In HLA-B5701+ individuals
Tenofovir Renal osteomalacia, flare of hepatitis in HBV-coinfected patients
who discontinue drug
Nucleoside/Neucleotide Reverse Transcriptase Inhibitors

8. Non-Nucleoside Reverse Transcriptase Inhibitors
Drugs Common side effects Doses
Delavirdine Skin rash, abnormal LFT 400 tid
Nevirapine Skin rash, hepatotoxicity 200 mg/d x 14 days then 200
mg bid
Efavirenz Rash, dysphoria, abnormal LFT,
drowsiness, abnormal dreams,
depression, lipid abnormalities,
teratogenic
600 mg qhs
Etravirine Rash, nausea, hypersensitivity
reactions
200 bid
Rilpivirine Nausea, dizziness, vertigo 25 mg qd

9. Protease Inhibitors
Saquinavir
Indinavir
Nelfinavir
Amprenavir
Lopinavir/Rotinavir
Darunavir
Fosamprenavir
Ritonavir
Tripanavir

10. Drugs Common side effects
Saquinavir Hyperbilirubinemia
PR prolongation
GI symptoms
Hyperglycemia
fat maldistribution
Rash
Transaminase elevations
Nephrolithiasis
Hepato-toxicity
1000 mg + 100 mg ritonavir
bid
Indinavir 800 mg q8h or 800 + 100 mg
ritonavir bid or 1000 mg q8h
when used with efavirenz or
nevirapine
Nelfinavir 750 mg tid or 1250 mg bid
Amprenavir 1200 mg bid or 600 + 100 mg
ritonavir bid
Lopinavir/Rotinavir 400 mg/100 mg bid
Darunavir 600 + 100 mg ritonavir bid
Fosamprenavir 1400 mg bid or 700 + 100 mg
ritonavir bid or 1400 + 200
mg ritonavir qd
Protease Inhibitors

11. Fusion Inhibitor
Enfuvirtide
Chemokine Receptor Antagonists
Maraviroc
Entry Inhibitors

12. Entry Inhibitors
Drugs Common side effects dose
Enfuvirtide  Local injection reactions
Hypersensitivity reactions
Increased rate of bacterial
pneumonia
90 mg bid
Maraviroc 150–600 mg bid

13. Integrase Inhibitors

14. Integrase Inhibitors
Drugs Common side effects Dose
Raltegravir GI symptoms
Headache
CPK elevation
Muscle weakness &
rhabdomyolysis
400 mg bid
Elvitegravir 150 mg qd

15. WHO clinical stages

16. WHO clinical stages

17. Recommended and desirable laboratory tests at ART initiation
Recommended
CD 4 cell count
Desirable
Hb test for Zidovudine
Pregnancy test
Blood pressure measurement
Urine dipsticks for glycosuria and estimated glomerular filtration rate
(eGFR) and serum creatinine for Tenofovir
Alanine aminotransferase for NVP

18. When to Initiate ART

19. First line ART for adults
2 NRTI’s
Lamivudine (3TC)
or
Emtricitabine(FTC)
Tenofovir (TDF)
1 NNRTI
Efavirenz (EFV)
IF CONTRAINDICATED
Zidovudine (AZT) + Lamivudine (3TC) + Efavirenz (EFV)
Zidovudine (AZT) + Lamivudine (3TC) + Nevirapine (NVP)
Zidovudine (AZT) + Lamivudine (3TC) / Emtricitabine (FTC) + Nevirapine (NVP)
OR
OR

20. Follow up of patients on ART
Recommended and desirable laboratory tests patient on ART
Recommended
CD4 cell count (every 6 months)
HIV viral load (at 6months after initiating ART and every 12 months
thereafter)
Desirable
Urine dipstick for glycosuria and serum creatinine for TDF

21. Indications for Changing ART in Patients with HIV Infection
Less than a 1-log drop in plasma HIV RNA by 4 weeks following
the initiation of therapy
A significant increase (defined as threefold or greater) plasma
HIV RNA level
Persistently declining CD4+ T cell numbers
Clinical deterioration
Side effects

22. Second line ART for adults
2 NRTIs + Ritonavir-boosted (PI)
TDF + 3TC (or FTC) FAILS Zidovudine (AZT) + Lamivudine (3TC)
AZT or d4T + 3TC FAILS Tenofovir (TDF) + Lamivudine(3TC) /
Emtricitabine (FTC)
Atazanavir + ritonavir (ATV/r)
Lopinavir/ritonavir (LPV/r)

23. Guidelines for Prevention of OI’s in Persons Infected with HIV
Pathogen Indication Drugs
Pneumocystis jiroveci CD4+ T cell count <200/L
Oropharyngeal candidiasis
Prior bout of PCP
TMP-SMX (TMP: 5 mg/kg;
SMX: 25 mg/kgb) qd
Myc. TB INH sensitive Skin test >5 mm
Prior +ve test without T/t
Close contact with active
Pul TB
(INH 300mg PO
+Pyridoxine 50mg PO) qd x
9 months
INH 900 mg PO twice wkly
+ Pyridoxine 50 mg PO daily
x 9 months
INH resistant Rifabutin 300 mg or
Rifampin 600 mg PO qd x4
months
MAC CD4+ T cell count <50/L AZT 1200 mg qw PO
Clarithromycin 500mg bid

24. Pathogen Indications Drugs
Toxoplasma
gondii
TOXO IgG antibody positive
CD4+ T cell count <100/L
TMP/SMX 1 DS tablet PO qd
Prior toxoplasmic encephalitis
CD4+T cell count <200/L
Sulfadiazine 500–1000mg qid PO
+Pyrimethamine 25–50 mg/d PO
+ Leucovorin 10–25 mg/d PO
VZ virus Exposure to chickenpox or
shingles in a pt. with no history
of immunization or prior
exposure
VZ immune globulin, IM, within
96h
Cryptococcus
neoformans
Prior documented disease Fluconazole 200 mg/d PO
CMV Prior end-organ disease
Restart if prior retinitis &
CD4+ T cells <100/L
Valganciclovir 900 mg bid PO
Ganciclovir SR implant q6–9
months + Valganciclovir 900 mg
bid
Guidelines for Prevention of OI’s in Persons Infected with HIV

25. Pathogen Indications Drugs
Herpes simplex Frequent/severe
recurrences
Valacyclovir 500 mg bid PO
Acyclovir 400 mg bid PO
Famciclovir 500 mg bid PO
Candida Frequent/severe
recurrences
Fluconazole 100–200 mg/d PO
Guidelines for Prevention of OI’s in Persons Infected with HIV

26. Thank you