improving adherence with simplified haart regimens improving clinical outcomes in hiv patients

Improving Adherence With Simplified HAART Regimens

Improving Clinical Outcomes in HIV Patients

Adherence to HAART Is Essential

“Adherence to the [HAART] regimen is essential for successful treatment and has been reported to increase sustained virologic control, which is critical in reducing HIV-related morbidity and mortality.”1

“Conversely, suboptimal adherence has been reported to decrease virologic control and has been associated with increased morbidity and mortality. Suboptimal adherence also leads to drug resistance, limiting effectiveness of therapy.”1

1. DHHS. Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents . Mar 23, 2004:9.

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Relationship Between Adherence and HIV Suppression

*Series of 886 treatment-naive HIV patients;CD4 cell count <500 x 106 cells/L or plasma viral load >5000 copies/mL.

†Prospective, observational study of 81 HIV patients.‡MEMS, Medication Events MonitoringSystem.

1. Low-Beer S et al. JAIDS. 2000;23:360-361. Letter. 2. Paterson DL et al. Ann Intern Med. 2000;133:21-30.

2

Relationship Between Adherence and CD4 Cell Count

*Observational and research study of 1522 ART-naive patients initiated on HAART; adherence was measured as prescriptions refilled.

1. Wood et al. JAIDS. 2004;35:261-268.

Homer Study*1

3

Virological Response by Daily Pill Burden*1

1. Bartlett JA et al. AIDS. 2001;15:1369-1377.4

* Symbol size is directly proportional to weight of the data point in analysis.

Adherence Impacts HIV-Related Mortality and AIDS Progression*1

*Prospective, observational study of 950 ART-naive patients treated with triple- combination therapy; adherence was estimated by prescriptions dispensed.

1. Hogg et al. 7th CROI 2000. Abstract 73.

For every 10% decrease in adherence

1.17 times higher likelihood of progression

to AIDS and/or death

5

16% increase in HIV-related mortality

Regimen-Related Drivers of Adherence1


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HAART Patients Commonly Miss Doses Due to Side Effects*1

1. Munk. CPS Info Pack (suppl). POZ. 1998.

*Community Prescription Service (CPS) phone survey of 400 people with HIV, most of whom were on triple combination therapy.

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ART-Related Toxicities Are the Largest Cause of Discontinuation

Major Reasons for HAART Discontinuation

1. O’Brien et al. JAIDS. 2003;34:407-414. 2. Monforte et al. AIDS. 2000;14:499-507.

*Retrospective study of 345 ART-naive patients initiated on HAART and followed fora median of 8.1 months; 211 patients (61%)discontinued therapy.

†Population-based cohort of 862 ART-naive patients initiated on HAART and followed fora median of 45 weeks; 312 patients (36%)discontinued therapy.

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Nausea Often Results in HAART Discontinuation*1

*Retrospective study of 345 ART-naive patients initiated on HAART and followed for amedian of 8.1 months. Of 211 patients who discontinued therapy, 40% did so due to AEs.

1. O’Brien et al. JAIDS. 2003;34:407-414.9

Patients Prefer QD HAART Regimens*1

*Survey of 536 HIV+ patients conducted via telephone, Internet, and mailduring 2001 to 2002.

1. Bass, Smith. XIV Intl AIDS Conf (IAC) 2002. Abstract MoPeB3290.10

Once-Daily Regimens May Improve Adherence*1

*Percentage of patients reporting they have forgotten doses among 504 patients who underwent standardized interviews; APPT-1 pan-European survey.

1. Moyle et al. 6th Intl Congress on Drug Ther in HIV Inf 2002. Poster 99.11

ART Agents FDA-Approved for QD Dosing1

1. Adapted from: DHHS. Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents . Mar 23, 2004:21.

Non-Nucleoside Reverse Transcriptase

Inhibitor (NNRTI)

Nucleoside Reverse Transcriptase Inhibitor

(NRTI)Protease Inhibitor (PI)

Efavirenz (EFV) Didanosine (ddI) EC Atazanavir (ATV)

Tenofovir disoproxil fumarate (TDF)

Amprenavir (APV)/ ritonavir (RTV)

Lamivudine (3TC)Fosamprenavir (FPV)/

ritonavir (RTV)

Stavudine (d4T) XR

Emtricitabine (FTC)

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NRTIs and Food Restrictions1

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1. DHHS. Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents. Mar 23, 2004:59.

Generic Name/Trade Name Food Effect

Abacavir (ABC) Ziagen® Take without regard to meals; Alcohol increases abacavir levels 41%; has no effect on alcohol

Didanosine (ddI) Videx®, Videx EC® Levels decrease 55%; Take 1/2 hour before or 2 hours after meal

Emtricitabine (FTC) Emtriva™ Take without regard to meals

Lamivudine (3TC) Epivir® Take without regard to meals

Stavudine (d4T) Zerit® Take without regard to meals

Tenofovir Disoproxil Fumarate Viread® Take without regard to meals

Zalcitabine (ddC) Hivid® Take without regard to meals

Zidovudine (AZT, ZDV) Retrovir® Take without regard to meals

NNRTIs and Food Restrictions1



Delavirdine/Rescriptor®

Take without regard to meals

Efavirenz/Sustiva®

High-fat/high-caloric meals increase peak plasma concentrations of capsules by 39% and tablets by 79%; take on an empty stomach

Nevirapine/Viramune® Take without regard to meals

PIs and Food Restrictions1


Amprenavir/Agenerase®

High-fat meal decreases blood concentration curve 21%; can be taken with or without food, but high fat meal should be avoided.

Atazanavir/Reyataz™Administration with food increases bioavailability. Take with food

Fosamprenavir (f-APV)/Lexiva™No significant change in amprenavir pharmacokinetics in fed or fasting state

Indinavir/Crixivan®

Levels decrease 77%. Take 1 hour before or 2 hours after meals; may take with skim milk or low-fat meal


PIs and Food Restrictions1 (continued)


Lopinavir +Ritonavir/Kaletra®

Moderate fat meal Increases AUC of capsules and solution by 48% and 80%, respectively.Take with food.

Nelfinavir/Viracept® Levels increase 2-3 fold. Take with meal or snack

Ritonavir/Norvir®Levels increase 15%. Take with food if possible;

this may improve tolerability

Saquinavir hard gel capsule/Invirase® No food effect when taken with ritonavir

Saquinavir soft gel capsule/Fortovase® Levels increase 6-fold. Take with large meal


Recommendations for Once-Daily Therapy

“The Panel recommends once-daily dosing with antiretroviral agents that have pharmacokinetic profiles that justify once-daily use (didanosine, lamivudine, tenofovir, efavirenz and atazanavir)....Once-daily therapy is desired for patient convenience and adherence.”*1


15

Half-lives of NRTIs1

14

1. DHHS. Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents . Mar 23, 2004:59-60, Table 15.

* XR, extended release.

Half-lives of Once-Daily NRTIs1

1. DHHS. Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents . Mar 23, 2004:59-60, Table 15.

14

* XR, extended release.

NRTI Product Loyalty in 2003

1. NDC Retail Pharmacy Patient Database, Update Feb. 2004.

Patient Persistency in December 2003January 2003 New to Product Patients1

Conclusions

HAART adherence in HIV+ patients may improve with simplified regimens1

Once-daily regimens may improve patient adherence1 and virologic suppression2-4

ART agents with pharmacokinetic profiles that support once-daily use are recommended5

ART-related toxicities are the leading cause of compromised adherence/discontinuation6-7 and should be considered in the selection of HIV treatment

1. Moyle G et al. 6th Intl Congress on Drug Ther in HIV Inf 2002. Poster 99. 2. Low-Beer S et al. JAIDS. 2000; 23:360-361. Letter. 3. Paterson DL et al. Ann Intern Med. 2000;133:21-30. 4. Bartlett J et al. 7th CROI 2000. Abstract 519. 5. DHHS. Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents . Mar 23, 2004:20. 6. O’Brien ME et al. JAIDS. 2003;34:407-414. 7. Monforte A et al. AIDS. 2000;14:499-507.

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improving adherence with simplified haart regimens improving clinical outcomes in hiv patients

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