C5 Case Study Session of Three Long-Term Survivors with HIV Disease Jayaweera

Case Reports on

Long term Survivors

D.T Jayaweera M.D.Professor of MedicineInfectious DiseasesUniversity of MiamiSchool of Medicine

Case Study - 1Case Study - 1

Case StudyCase Study 35 year old W/M presented for 35 year old W/M presented for

possible liver transplantation in Jan possible liver transplantation in Jan 2005.2005.

He had been diagnosed with HIV He had been diagnosed with HIV over 10 years ago and now he was in over 10 years ago and now he was in end stage AIDS with hemophilia, end stage AIDS with hemophilia, HCV/ HBV.HCV/ HBV.

His Child Pugh class was C and the His Child Pugh class was C and the MELD Score was over 28.MELD Score was over 28.

Case StudyCase Study The CD4 cell count was 69 The CD4 cell count was 69

cells/mm3 and the HIV VL was over cells/mm3 and the HIV VL was over 100,000 copies/ml100,000 copies/ml

Patient had severe ascites. Patient had severe ascites. His bilirubin was over 17 mg% and His bilirubin was over 17 mg% and

his Albumin was 2 g/dl, and the INR his Albumin was 2 g/dl, and the INR was 2.4. The other labs were was 2.4. The other labs were unremarkable.unremarkable.

Audience Response Audience Response QuestionsQuestions

The factors affecting the Child Pugh The factors affecting the Child Pugh score include the following.score include the following.

1. INR, bilirubin and Ascites1. INR, bilirubin and Ascites

2. INR, creatinine, bilirubin and 2. INR, creatinine, bilirubin and hemoglobinhemoglobin

3. ALT, bilirubin, creatinine, hemogobin 3. ALT, bilirubin, creatinine, hemogobin

4. INR, bilirubin and ascites, ALT4. INR, bilirubin and ascites, ALT

5. INR, bilirubin and ascites, creatinine 5. INR, bilirubin and ascites, creatinine encephalopathy,encephalopathy,


The factors affecting the Child Pugh The factors affecting the Child Pugh score include the following.score include the following.

1. INR, bilirubin and Ascites1. INR, bilirubin and Ascites

2. INR, creatinine, bilirubin and 2. INR, creatinine, bilirubin and hemoglobinhemoglobin

3. ALT, bilirubin, creatinine, hemogobin 3. ALT, bilirubin, creatinine, hemogobin

4. INR, bilirubin and Ascites, ALT4. INR, bilirubin and Ascites, ALT

5. 5. INR, bilirubin and Ascites, creatinine INR, bilirubin and Ascites, creatinine encephalopathyencephalopathy,,

Child-Pugh ScoreChild-Pugh Score

Child-Pugh Score Child-Pugh Score CalculatorCalculator

Measure 1 point 2 points 3 points units

Bilirubin <34 (<2) 34-50 (2-3) >50 (>3)μmol/l (mg/dl)

Albumin >35 28-35 <28 g/l

INR <1.7 1.71-2.20 > 2.20 no unit

Ascites None Mild Severe no unit

Encephalopathy

None

Grade I-II (or suppressed with medication)

Grade III-IV (or refractory)

no unit

MELD SCOREMELD SCORE

MELD uses serum MELD uses serum bilirubin, , creatinine, , and and INR to predict survival. to predict survival.

If the patient has been If the patient has been dialyzed twice twice within the last 7 days, then the value for within the last 7 days, then the value for serum creatinine used should be 4.0 serum creatinine used should be 4.0

3 month mortality is3 month mortality is::

40 or >40 — 100% mortality 40 or >40 — 100% mortality

30 – 39 —- 83% mortality ; 20 – 29 — 30 – 39 —- 83% mortality ; 20 – 29 — 76% mortality 10–19 — 27% mortality 76% mortality 10–19 — 27% mortality <10 — 4% mortality <10 — 4% mortality

Case StudyCase Study

This patient was on ddI, D4T and This patient was on ddI, D4T and EpivirEpivir

He was intolerant to Lopinavir due to He was intolerant to Lopinavir due to his hemophilia as it caused joint his hemophilia as it caused joint bleeds.bleeds.

The HIV phenotype was pan sensitive The HIV phenotype was pan sensitive to the PI class, and few mutations on to the PI class, and few mutations on NRTIs and NNRTIs. NRTIs and NNRTIs.

Patients medications were changedPatients medications were changed


Based on the phenotype this patient Based on the phenotype this patient would be best treated with the would be best treated with the following (this is 2005)following (this is 2005)

1. Lopinavir/r, abacavir, epivir1. Lopinavir/r, abacavir, epivir 2. fosamprenavir/ ritonavir / abacavir, 2. fosamprenavir/ ritonavir / abacavir,

epivirepivir 3. Atazavir, combivir3. Atazavir, combivir 4. Efavirenz, truvada4. Efavirenz, truvada Any Boosted PI with truvadaAny Boosted PI with truvada


Based on the phenotype this patient Based on the phenotype this patient would be best treated with the would be best treated with the following (this is 2005)following (this is 2005)

1. Lopinavir/r, abacavir, epivir1. Lopinavir/r, abacavir, epivir 2. fosamprenavir/ ritonavir / abacavir, 2. fosamprenavir/ ritonavir / abacavir,

epivirepivir 3. Atazavir, combivir3. Atazavir, combivir 4. Efavirenz, truvada4. Efavirenz, truvada Any Boosted PI with truvadaAny Boosted PI with truvada

Critical decisionsCritical decisions

What HAART regimen would you What HAART regimen would you start?start?

Will you consider a liver transplant in Will you consider a liver transplant in this patient?this patient?

What complications do you anticipate What complications do you anticipate if he gets a liver transplant?if he gets a liver transplant?

How will hemophilia affect the How will hemophilia affect the transplant and transplant affect the transplant and transplant affect the hemophilia?hemophilia?

Is HBsAg present?Is HBsAg present?

Is IgM anti-HBc present?Is IgM anti-HBc present?

Is HBeAg or HBV DNA present?Is HBeAg or HBV DNA present?Is anti-HBs present?Is anti-HBs present?

Chronic Chronic HepatitisHepatitis

Acute Acute HepatitisHepatitis

Replicative HBV Replicative HBV infectioninfection

Non-replicative Non-replicative HBV infectionHBV infection

Recovered or Recovered or vaccinated vaccinated

+/- anti-HBc+/- anti-HBc

No HBV No HBV infectioninfection

NoNo

YesYes

YesYes

YesYes

YesYes

NoNo

NoNoNoNo

Anti-HBc Anti-HBc +/-+/-

nonoyesyes

Clinical Liver Disease Clinical Liver Disease and HBV Genotypeand HBV Genotype

Duong TN, et al. Journal of Medical Virology. 2004;72:551–557.

Diagnosis, n (%)

Genotypes N Asymptomatic carrier

Chronic hepatitis

Liver cirrhosis

HCC

Genotype A 11 8 (72.7) 3 (27.3) 0 0

Genotype B 14 10 (71.4) 3 (21.4) 0 1 (7.2)

Genotype C 350 129 (36.8) 126 (36.0) 50 (14.3) 45 (12.9)

Genotype D 38 32 (84.2)b 6 (15.8)a 0 0a

a P<0.05 vs genotype C.b P<0.001 vs genotype C.

Treatment of HBV in HIVTreatment of HBV in HIV

Always start with emtricitabine/tenofovir Always start with emtricitabine/tenofovir If the patient has been on lamivudine add If the patient has been on lamivudine add

tenofovirtenofovir If the patient is on Epzicom change to If the patient is on Epzicom change to

emtricitabine/tenofoviremtricitabine/tenofovir If the patient has renal failure or low GFR If the patient has renal failure or low GFR

<60 it is safer to use lamivudine or <60 it is safer to use lamivudine or emtricitabine with entecavir than using emtricitabine with entecavir than using dose adjusted emtricitabine/tenofovir dose adjusted emtricitabine/tenofovir

To reduce the risk for transmission, To reduce the risk for transmission, HBsAg-positive persons should:HBsAg-positive persons should:

Use condoms to protect nonimmune sex partners. Use condoms to protect nonimmune sex partners. Refrain from donating blood, plasma, tissue, or semen. Refrain from donating blood, plasma, tissue, or semen. HBsAg-positive pregnant women should be advised their HBsAg-positive pregnant women should be advised their

newborns to receive hepatitis B vaccine and hepatitis B newborns to receive hepatitis B vaccine and hepatitis B immune globulinimmune globulin

To protect the liver HBsAg-positive persons should be advised To protect the liver HBsAg-positive persons should be advised to avoid or limit alcohol consumption, vaccination against to avoid or limit alcohol consumption, vaccination against hepatitis A. hepatitis A.

15%--25% of persons with chronic HBV 15%--25% of persons with chronic HBV infection are at risk for premature infection are at risk for premature death from cirrhosis and liver cancer, death from cirrhosis and liver cancer,

Add another drug

without cross resistance

Monitor every 3 months

Addanother drug

orContinue

Monitor every 3 months

Continue Monitor every 6 months

Management Roadmap Management Roadmap According to 24 Week According to 24 Week

Virologic ResponseVirologic Response

Inadequate response>104 copies/mL

Complete response <300 copies/mL

Partial response 300-104 copies/mL

Week 24: Early predictors of efficacy

Keeffe et al. Clin Gastroenterol Hepatol, 2007

Monitoring for Drug Monitoring for Drug ResistanceResistanceAll patients All patients

HBV DNA and ALT at baseline and at 3 months HBV DNA and ALT at baseline and at 3 months after starting therapy (assess antiviral efficacy)after starting therapy (assess antiviral efficacy)

Mild liver diseaseMild liver disease HBV DNA and ALT q 6 mo for first 2 years; HBV DNA and ALT q 6 mo for first 2 years;

thereafter q 3 mo and at any change in therapythereafter q 3 mo and at any change in therapy

Advanced liver disease/cirrhosisAdvanced liver disease/cirrhosis HBV DNA and ALT q 3 mo with clinical evaluationHBV DNA and ALT q 3 mo with clinical evaluation

Locarnini S, et al. Antiviral Ther. 2004;9:679-693.

Hepatitis B VirusHepatitis B VirusWild Type and MutantsWild Type and Mutants

Wild typeWild type Usual HBeAg (+) hepatitisUsual HBeAg (+) hepatitis

Precore mutation (27% U.S. patients)Precore mutation (27% U.S. patients)11

Abolishes HBeAg productionAbolishes HBeAg production Core promoter mutation (44% U.S. patients)Core promoter mutation (44% U.S. patients)11

Down-regulates HBeAg productionDown-regulates HBeAg production Treatment-induced mutationsTreatment-induced mutations22

Lamivudine: L180M +/- M204V/I (YMDD)Lamivudine: L180M +/- M204V/I (YMDD) Adefovir: N236T and A181VAdefovir: N236T and A181V Entecavir: I169, T184, S202 and M250 (LAMEntecavir: I169, T184, S202 and M250 (LAMRR

patients)patients) Telbivudine: M204I Telbivudine: M204I

1Chu CJ, et al. Gastroenterology. 2003;125:444-451.2Keeffe EB, et al. Clin Gastroenterol Hepatol. 2006;4:936-962.


This patient was started on fosamprenavir/ This patient was started on fosamprenavir/ ritonavir / truvada and after 2 days due to ritonavir / truvada and after 2 days due to excessive vomiting this was changed to excessive vomiting this was changed to atazanavir/ ritonavir/truvada/fusion inhibitor.atazanavir/ ritonavir/truvada/fusion inhibitor.

After 4 weeks the VL came down to 3940 and After 4 weeks the VL came down to 3940 and the CD4 cell count went up to 97cells/mm3the CD4 cell count went up to 97cells/mm3

Insurance refused to pay for surgery and Insurance refused to pay for surgery and after many appeals agreed and the after many appeals agreed and the transplant was performed within 6 weeks of transplant was performed within 6 weeks of the first encounter the first encounter


Post transplant, patient was started on Post transplant, patient was started on steroids, PPI and prografsteroids, PPI and prograf

Prograf ( for immunosuppression) is Prograf ( for immunosuppression) is metabolized via CYP P450 3A4 systemmetabolized via CYP P450 3A4 system

Post operative GFR decreased to < 40Post operative GFR decreased to < 40 Patient made an unremarkable recovery.Patient made an unremarkable recovery.


Following are true:Following are true: 1. Atazanavir can not be used with PPI 1. Atazanavir can not be used with PPI

and hence need to be changedand hence need to be changed 2. Truvada should be given to treat 2. Truvada should be given to treat

HBVHBV 3. Hemophilia will be cured by liver 3. Hemophilia will be cured by liver

transplanttransplant 4. 1 and 2 are correct4. 1 and 2 are correct 5. All are correct5. All are correct


Following are true:Following are true: 1. Atazanavir can not be used with PPI 1. Atazanavir can not be used with PPI

and hence need to be changedand hence need to be changed 2. Truvada should be given to treat 2. Truvada should be given to treat

HBVHBV 3. Hemophilia will be cured by liver 3. Hemophilia will be cured by liver

transplanttransplant 4. 1 and 2 are correct4. 1 and 2 are correct 5. 5. All are correctAll are correct


The patient had an uneventful post op The patient had an uneventful post op period and at the end of one year the CD4 period and at the end of one year the CD4 cell count had increased up to 149 cells cell count had increased up to 149 cells and the HIV VL was 3900 /mm3and the HIV VL was 3900 /mm3

Patient managed to get Darunavir on Patient managed to get Darunavir on compassionate access program and with compassionate access program and with that the VL came down to<50 copiesthat the VL came down to<50 copies

It was noted that HBV VL, with e ag It was noted that HBV VL, with e ag positive at the beginning had the HBV VL positive at the beginning had the HBV VL undetectable at one year.undetectable at one year.

ARTEMIS: Darunavir + ARTEMIS: Darunavir + Ritonavir Versus Ritonavir Versus

Lopinavir/RitonavirLopinavir/Ritonavir

Mills A, et al. 48th ICAAC. Washington, DC, 2008. Abstract H-1250c.

Darunavir + RTV (n=343)

Lopinavir/r(n=346)

Virologic failure (%) 12* 17

HIV RNA<50 copies/mL (%)

79† 71

By baseline HIV RNA

<100K copies/mL >100K copies/mL

81 (n=226)76‡ (n=117)

75 (n=226)63 (n=120)

All patients received emtricitabine/tenofovir DF.Virologic failure: >50 copies/mL.

*P=0.0437 versus lopinavir/r.†P<0.001 for non-inferiority to lopinavir/r.

‡P=0.023 versus lopinavir/ritonavir.

Week 96 Outcomes

ARTEMIS:ARTEMIS:96-Week Tolerability 96-Week Tolerability

ResultsResults

All patients received emtricitabine/tenofovir DF.*P<0.001 versus lopinavir/r.†P=0.0016 versus lopinavir/r.

‡P<0.0001 versus lopinavir/ritonavir.

Darunavir + RTV(n=343)

Lopinavir/r(n=346)

Grade 2-4 adverse events Diarrhea Nausea Rash (all types)

4*23

1131

Grade 2-4 lipid abnormalities Total cholesterol LDL-C Triglycerides

18†184‡

281513

Mills A, et al. 48th ICAAC. Washington, DC, 2008. Abstract H-1250c.


Two years ago when raltegravir was Two years ago when raltegravir was made available the fusion inhibitor made available the fusion inhibitor was discontinued and he was given was discontinued and he was given raltegravir 400mg twice a dayraltegravir 400mg twice a day

Patient tolerated this very well.Patient tolerated this very well. Now it is 5 years since his liver Now it is 5 years since his liver

transplanttransplant


We have cured him of his We have cured him of his HEMOPHILIAHEMOPHILIA

We have completely suppressed HIV We have completely suppressed HIV with the VL being continuously with the VL being continuously undetectable for the last 4 years.undetectable for the last 4 years.

We have completely suppressed HBV We have completely suppressed HBV and he has HBV surface AB Positiveand he has HBV surface AB Positive

His HCV is still active and we are His HCV is still active and we are awaiting new treatment for HCV.awaiting new treatment for HCV.

Problems Associated Problems Associated with Liver with Liver

Transplantation in HIVTransplantation in HIV Immune suppression and T cell Immune suppression and T cell

activationactivation Drug Interactions - PK interactionsDrug Interactions - PK interactions Prescribing errorsPrescribing errors Co infection with HCV and HBVCo infection with HCV and HBV Use of antacidsUse of antacids Renal problemsRenal problems

Case Study - 2Case Study - 2

Case StudyCase Study 37Y old AAF was 137Y old AAF was 1stst seen in Jan 97 with HIV. seen in Jan 97 with HIV.

She had tested + in 1996. Risk – Hetero sexual She had tested + in 1996. Risk – Hetero sexual and crack use. She had a P/H psoriasis and and crack use. She had a P/H psoriasis and HSVHSV

Quit Crack and ethanol abuse in 1996 . Patient Quit Crack and ethanol abuse in 1996 . Patient started on AZT/3TC/Crixivan , Zithromax and started on AZT/3TC/Crixivan , Zithromax and pentamadine (prophylaxis)pentamadine (prophylaxis)

Allergy to bactrimAllergy to bactrim Psoriasis treated with steroid creams.Psoriasis treated with steroid creams. She was never really compliant. Had an She was never really compliant. Had an

abusive partnerabusive partner

Case StudyCase Study VL was 5000-200,000/ml CD4 36 -52/mlVL was 5000-200,000/ml CD4 36 -52/ml Changed to Efavirenz, ddI and Ziagen in Changed to Efavirenz, ddI and Ziagen in

7/997/99 Admitted to Hospital with PCP in 4/2000Admitted to Hospital with PCP in 4/2000 Changed to Efavirenz, ddI, D4T and Ziagen Changed to Efavirenz, ddI, D4T and Ziagen

5/005/00 1/01 changed to kaletra 3 bid/amprenavir 4 1/01 changed to kaletra 3 bid/amprenavir 4

bid/Zerit/epivir 1/01 and 6/01 CD4 13/ml bid/Zerit/epivir 1/01 and 6/01 CD4 13/ml HIV VL >760k HIV VL >760k

Depression – started EffexorDepression – started Effexor

Case StudyCase Study 2/02 Kaletra/abacavir/videx EC/viread 2/02 Kaletra/abacavir/videx EC/viread

CD4 21 VL >750KCD4 21 VL >750K 2/03 Viramune/videxEC/viread/ziagen 2/03 Viramune/videxEC/viread/ziagen

CD4 59/ml, VL 148911/mlCD4 59/ml, VL 148911/ml 5/03 admitted to JMH with headache 5/03 admitted to JMH with headache

and right sided hemi paresis CT brain and right sided hemi paresis CT brain and brain biopsy were done later and brain biopsy were done later

Developed sudden onset of left eye Developed sudden onset of left eye blindness blindness


Based on these findings most likely Based on these findings most likely diagnoses will includediagnoses will include

1.1. CNS toxoplasmosisCNS toxoplasmosis

2.2. CNS lymphomaCNS lymphoma

3.3. CMV retinitisCMV retinitis

4.4. Retinal detachmentRetinal detachment

5.5. 2 and 3 only2 and 3 only

6.6. All of the above except 5.All of the above except 5.


Based on these findings most likely Based on these findings most likely diagnoses will includediagnoses will include

1.1. CNS toxoplasmosisCNS toxoplasmosis

2.2. CNS lymphomaCNS lymphoma

3.3. CMV retinitisCMV retinitis

4.4. Retinal detachmentRetinal detachment

5.5. 2 and 3 only2 and 3 only

6.6. All of the above except 5.All of the above except 5.


CT scan of the brain showed multiple ring CT scan of the brain showed multiple ring enhancing lesions.enhancing lesions.

Patient was diagnosed with CNS Patient was diagnosed with CNS toxoplasmosis and started on toxoplasmosis and started on sulfadiazine/pyrimethamine and folinic sulfadiazine/pyrimethamine and folinic acid. acid.

After treating for 2-3 weeks the CNS After treating for 2-3 weeks the CNS lesions improved except for one lesion.lesions improved except for one lesion.

Brain biopsy was done and it showed CNS Brain biopsy was done and it showed CNS lymphoma. lymphoma.


The patient was seen by the ophthalmologist The patient was seen by the ophthalmologist and diagnosed CMV retinitis and was and diagnosed CMV retinitis and was started on gancyclovir. Few days later she started on gancyclovir. Few days later she developed right eye blindness which was developed right eye blindness which was diagnosed as retinal detachment but treated diagnosed as retinal detachment but treated was unsuccessful.was unsuccessful.

This patient had been non complaint with This patient had been non complaint with HAART medications and having CNS toxo, HAART medications and having CNS toxo, lymphoma and CMV retinitis and hence, it lymphoma and CMV retinitis and hence, it was decided top send the patient to hospice.was decided top send the patient to hospice.


Patient RTC from hospice and requested “ Patient RTC from hospice and requested “ not to give up on her”not to give up on her”

Started treatment for CNS Lymphoma with Started treatment for CNS Lymphoma with IL2, Radiation to th ebrain, GCV/ HAART IL2, Radiation to th ebrain, GCV/ HAART with high dose AZT, RTX to the brainwith high dose AZT, RTX to the brain

Responded to this regimen. 1/04 Kaletra/ Responded to this regimen. 1/04 Kaletra/ invirase/Fuzeon/combivir and later invirase/Fuzeon/combivir and later changed to high dose Kaletrachanged to high dose Kaletra

CD 4 then increased to 116(9%) and VL CD 4 then increased to 116(9%) and VL decreased to 4620 /mldecreased to 4620 /ml


Patient later enrolled in a study and Patient later enrolled in a study and received Darunavir/ritonavir/truvada / received Darunavir/ritonavir/truvada / fuzeon and the HIV VL became undetectable fuzeon and the HIV VL became undetectable and the CD4 slowly went up to 761/ml (29% and the CD4 slowly went up to 761/ml (29% ))

This patient was always obese. Her height This patient was always obese. Her height was 5 feet 6 inches and the weight 180 lbs. was 5 feet 6 inches and the weight 180 lbs. During this time this patient became obese During this time this patient became obese and the obesity continued to get worse to and the obesity continued to get worse to 380lbs with hyperlipidemia, hypertension 380lbs with hyperlipidemia, hypertension and diabetes.and diabetes.

What is the cause of What is the cause of increased lipids in HIV increased lipids in HIV

patients?patients?HIV?HIV? Untreated HIV is Untreated HIV is

associated with high TG associated with high TG and low HDL and LDL, and low HDL and LDL, similar to other chronic similar to other chronic inflammatory diseasesinflammatory diseases

Treatment?Treatment? LDL-C tends to go up with LDL-C tends to go up with

virtually all regimensvirtually all regimens PIs:PIs: boosted PI regimens boosted PI regimens

increase TG increase TG and nonand non––HDL-C, HDL-C, but HDL-C typically increases but HDL-C typically increases as wellas well

NNRTIs:NNRTIs: Increase HDL-C Increase HDL-C EFV greater LDL-C and EFV greater LDL-C and TG TG

increases increases than NVPthan NVP

NRTIs:NRTIs: d4T d4T increases TG increases TG more TDF (and ABC)more TDF (and ABC)

New classes:New classes: MVC and RAL MVC and RAL do not appear to adversely do not appear to adversely affect lipidsaffect lipids

Newer drugs are more lipid Newer drugs are more lipid friendlyfriendly

STARTMRK Metabolic Study: RAL STARTMRK Metabolic Study: RAL vs EFVvs EFV Randomized, double-blind Randomized, double-blind

study comparing RAL vs study comparing RAL vs EFV, both with TDF/FTCEFV, both with TDF/FTC

Week 96 lipids (all pts, Week 96 lipids (all pts, n=563)n=563) EFV increased TC, HDL-C, EFV increased TC, HDL-C,

LDL-C, TG, and glucose sig LDL-C, TG, and glucose sig

more than EFVmore than EFV No sig difference in No sig difference in

total/HDL chol ratiototal/HDL chol ratio Dexa substudy (n=111)Dexa substudy (n=111)

Overall, limb fat increased Overall, limb fat increased over timeover time

By week 96, 3/37 pts on By week 96, 3/37 pts on RAL, 2/38 on EFV had RAL, 2/38 on EFV had >20% loss of limb fat>20% loss of limb fat

DeJesus E, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 720.

‡ p <0.001* P =0.025

‡‡

‡

‡

*

18.2

17.0

18.1

17.7

Raltegravir Group 55 4037

Efavirenz Group 56 4638

Number of Contributing Patients

Mean Percent (%) Change (SE) in Appendicular Fat Over Time

Q1. After starting antiretroviral Q1. After starting antiretroviral therapy, which one of the following therapy, which one of the following

increases more your total cholesterol?increases more your total cholesterol?

1.1. TFV/FTC/EFVTFV/FTC/EFV

2.2. TFV/FTC/ATZ/rTFV/FTC/ATZ/r

3.3. ABC/3TC/EFVABC/3TC/EFV

4.4. ABC/3TC/ATZ/rABC/3TC/ATZ/r

Q1. After starting antiretroviral Q1. After starting antiretroviral therapy, which one of the following therapy, which one of the following

increases more your total cholesterol?increases more your total cholesterol?

1.1. TFV/FTC/EFVTFV/FTC/EFV

2.2. TFV/FTC/ATZ/rTFV/FTC/ATZ/r

3.3. ABC/3TC/EFVABC/3TC/EFV

4.4. ABC/3TC/ATZ/rABC/3TC/ATZ/r

A5224s design: Metabolic A5224s design: Metabolic substudy of A5202 substudy of A5202

A5224s

LIPIDSLIPIDSA5202: ATV/r vs. EFVA5202: ATV/r vs. EFV

MedianMedian Changes in Fasting Lipids (mg/dL) Changes in Fasting Lipids (mg/dL)

In low HIV RNA stratum, in comparison between ABC/3TC vs. TDF/FTC: significantly greater increase in TC, LDL, HDL with both EFV and ATV/r; greater increase in TG with ATV/r

Median Change in Fasting Lipids (Week 48, mg/dL)

Daar E, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 59LB.

TC LDL HDL TGABC/3TCATV/r 29 13 8 24EFV 40 21 12 15

P-value <0.001 0.002 <0.0

01 0.26

TDF/FTCATV/r 10 2 5 14EFV 22 10 8 13

P-value <0.001 0.002 <0.0

01 0.26


Later changed to Later changed to Darunavir/isentress/truvada and the last Darunavir/isentress/truvada and the last CD4 cell count is 741 (32%) and VL <50 CD4 cell count is 741 (32%) and VL <50 copies.copies.

Patients was also started on a diet, Patients was also started on a diet, exercise, lipitor for hyperlipidemia and exercise, lipitor for hyperlipidemia and metformin for type 2 diabetes mellitus. metformin for type 2 diabetes mellitus. Hypertension was treated with lisinoprilHypertension was treated with lisinopril

Diabetes, hypertension, an lipids are under Diabetes, hypertension, an lipids are under control but the weight has not come down.control but the weight has not come down.

Case SummaryCase Summary

PROBLEMS 5-10PROBLEMS 5-10

years agoyears ago End stage AIDSEnd stage AIDS CNS toxo plasmosisCNS toxo plasmosis CNS lymphomaCNS lymphoma CMV retinitisCMV retinitis Non compliance Non compliance

with medicationswith medications Drug abuse (crack Drug abuse (crack

cocaine)cocaine)

PROBLEMS now PROBLEMS now

Morbid obesity is Morbid obesity is 63.63.

HypertensionHypertension Diabetes type 2Diabetes type 2 HIVHIV

D.T Jayaweera M.D.Professor of MedicineInfectious Diseases

Thank

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C5 Case Study Session of Three Long-Term Survivors with HIV Disease Jayaweera