Massimo AndreoniAzienda Ospedaliera Universitaria Policlinico Tor Vergata, Roma

Riflessioni su STR nella prospettiva dei farmaci generici in HIV

Registrational Treatment-Naive Clinical Trials: Cross-Study Comparison*

HIV RNA <50 c/mL at Week 48

66686868686969707071

73767676777878

808282838484

868788

90

0 10 20 30 40 50 60 70 80 90 100

NRTI backboneFTC/TDF3TC/ABC qd3TC+ABC bid3TC/ZDV3TC+TDF

% of Patients with HIV-1 RNA <50 copies/mL at Week 48

*This slide depicts data from multiple studies published from 2004-2012. Not all regimens have been compared head-to-head in a clinical trial

STARTMRK RAL (n=281)8

CASTLE ATV+RTV (n=440)6

ABT 730 LPV/r qd (n=333)5

CASTLE LPV/r (n=443)6

GS 934 EFV (n=243)4

MERIT ES EFV (n=303)3

KLEAN LPV/r (n=444)14

ECHO/THRIVE EFV (n=546)10

ABT 730 LPV/r bid (n=331)5

GS-102 QUAD (n=348)11GS-103 QUAD (n=353)12

GS-103 ATV+RTV (n=355)12

GS-102 Atripla (n=352)11

MERIT ES MVC (n=311)3

ARTEMIS DRV+RTV (n=343)7

ECHO/THRIVE RPV (n=550)10

GS-903 EFV (n=299)9

STARTMRK EFV (n=282)8

GS 934 EFV (n=244)4

ARTEMIS LPV/r (n=346)7

KLEAN FPV/r (n=434)14

CNA 30024 EFV (n=324)13

CNA 30024 EFV (n=325)13

SOLO FPV/r (n=322)2

SOLO NFV (n=327)2 CNA 30021 EFV (n=386)1

CNA 30021 EFV (n=384)1

Naive

NNRTIAtripla

PIDRV/cob/FTC/7340

NIQUAD

STR: Strategie per ogni fase della terapia

Switch per tossicità

NNRTI Eviplera

PI DRV/cob/FTC/7340

NI QUAD - DLT/ABC/3TC

NNRTI Atripla

NI QUAD

NNRTI Eviplera

NNRTI Atripla

NNRTI Eviplera

PI DRV/cob/FTC/7340

NI DLT/ABC/3TC

Naive

NNRTIAtripla

PIDRV/cob/FTC/7340

NIQUAD

STR: Strategie per ogni fase della terapia

Switch per fallimento

PI DRV/cob/FTC/7340

NI QUAD – DLT/ABC/3TC

NNRTI Atripla

NI QUAD – DLT/ABC/3TC

NNRTI Eviplera

NNRTI Atripla

NNRTI Eviplera

PI DRV/cob/FTC/7340

NI DLT/ABC/3TC ?

EU Patent Expiry DatesHBV

Epivir Viramune Sustiva Kaletra Ziagen Emtriva Viread Prezista Reyataz Norvir Isentress Baraclude

Lamivudine Nevirapine EfavirenzLopinavir / ritonavir

Abacavir EmtricitabineTenofovir Disoproxil

Darunavir Atazanavir Ritonavir Raltegravir Entecavir

Typical core 5 EU Patent Expiry Date

08-Aug-11 23-Dec-12 20-Nov-13 Dec-13 28-Jun-14 31-Jan-16 25-Jul-17 23-Aug-18 02-Mar-19 Dec-13 20-Dec-22 16-Oct-16

Albania NoneAustralia 13-Mar-11 07-May-12 06-Aug-13 16-Dec-13 31-Jan-16 25-Jul-17 24-Aug-13 12-Jan-19 16-Dec-13 21-Oct-22 04-Oct-16Austria 28-Feb-11 05-Feb-13 20-Nov-13 16-Dec-13 28-Jun-14 31-Jan-16 25-Jul-17 Pending 03-Mar-19 16-Dec-13 21-Oct-22 16-Oct-16Belgium 28-Feb-11 05-Feb-13 20-Nov-13 13-Dec-15 28-Jun-14 31-Jan-16 25-Jul-17 24-Aug-18 03-Mar-19 28-Aug-06 02-Jan-23 16-Oct-16Bulgaria None 30-Jan-15 None 24-Jul-17 None 02-Mar-19 28-Aug-06 20-Dec-22 NoneCroatia 07-Aug-13 28-Aug-06Cyprus 14-Jul-13 None 09-Dec-19 None 28-Aug-06 21-Oct-22 NoneCzech Republic 27-Dec-11 02-Feb-15 None 21-Dec-10 20-Feb-17 None 22-Apr-17 28-Aug-06 20-Dec-22 NoneDenmark 08-Aug-11 23-Dec-12 20-Nov-13 29-Dec-13 28-Jun-14 31-Jan-16 25-Jul-17 24-Aug-18 02-Mar-19 29-Dec-13 20-Dec-22 16-Oct-16Estonia None None None 28-Aug-06 20-Dec-22 NoneFinland 07-Aug-11 23-Dec-12 20-Nov-13 27-Jun-14 20-Feb-17 25-Jul-17 12-Feb-18 02-Mar-19 28-Aug-06 21-Oct-22 18-Oct-16France 08-Aug-11 23-Dec-12 20-Nov-13 15-Dec-13 28-Jun-14 31-Jan-16 25-Jul-17 23-Aug-18 02-Mar-19 28-Aug-06 20-Dec-22 15-Oct-16Germany 08-Aug-11 23-Dec-12 20-Nov-13 17-Dec-13 28-Jun-14 31-Jan-16 25-Jul-17 12-Feb-18 22-Apr-17 17-Dec-13 22-Oct-22 17-Oct-11Greece 08-Feb-10 23-Dec-12 19-Nov-13 15-Dec-15 29-Jun-14 01-Feb-16 25-Jul-17 Pending 08-May-19 15-Dec-15 21-Dec-22 17-Oct-16Hungary 04-Sep-11 07-Aug-13 21-Dec-13 21-Dec-10 31-Jan-16 None 21-Dec-13 21-Oct-22 17-Oct-16Iceland None None None None 19-Dec-22 NoneIreland 27-Feb-11 19-Nov-13 None 27-Jun-14 25-Jul-17 Pending 15-Dec-13 19-Dec-22 30-Sep-16Israel 08-Feb-10 07-Aug-13 22-Dec-10Italy 08-Aug-11 04-Feb-13 20-Nov-13 14-Dec-15 09-Jul-14 31-Jan-16 25-Jul-17 24-Aug-18 02-Mar-19 28-Aug-06 20-Dec-22 16-Oct-16Latvia 28-Feb-11 None 26-Jun-14 None 28-Aug-06 20-Dec-22 NoneLiechtenstein 23-Dec-12 21-Oct-22 16-Oct-11Lithuania None None None 28-Aug-06 21-Dec-22 NoneLuxembourg 08-Aug-11 05-Feb-13 20-Nov-13 None 28-Jun-14 31-Jan-16 25-Jul-17 02-Mar-19 28-Aug-06 02-Jan-23 16-Oct-16Malta None None None 28-Aug-06Monaco 25-Jul-17Netherlands 07-Aug-11 22-Dec-12 20-Nov-13 19-Mar-16 07-Jul-14 31-Jan-16 25-Jul-17 Pending 01-Mar-19 28-Aug-06 19-Dec-22 16-Oct-11New Zealand 08-Feb-10 16-Nov-10 06-Aug-13 25-Jul-17 None 21-Oct-22 01-Oct-11Norway 28-Feb-11 23-Dec-12 20-Nov-13 12-Dec-15 31-Jan-16 03-Jul-18 22-Apr-17 None 21-Oct-22 17-Oct-16Poland 08-Feb-10 06-Aug-13 None Pending 20-Feb-17 None 22-Apr-17 28-Aug-06 18-Oct-11Portugal 08-Feb-10 09-Jan-15 21-Nov-13 15-Dec-15 10-Oct-16 31-Jan-16 25-Jul-17 25-Aug-18 03-Mar-19 16-Dec-13 21-Dec-22 14-Jan-19Romania 28-Jun-14 01-Jan-17 01-Jan-17 Pending 28-Aug-06 21-Dec-22 18-Oct-15Russia 06-May-12 04-Jun-12Slovakia 27-Dec-11 20-Mar-15 None 10-Nov-15 25-Jul-17 None 22-Apr-17 28-Aug-06 20-Dec-22 NoneSlovenia 28-Feb-11 20-Nov-13 None 02-Aug-15 None 02-Mar-19 28-Aug-06 20-Dec-22 NoneSpain 08-Feb-10 05-Feb-13 20-Nov-13 20-Mar-16 08-Jul-14 31-Jan-11 25-Jul-17 24-Aug-18 02-Mar-19 20-Mar-16 20-Dec-22 16-Oct-16Sweden 07-Aug-11 22-Dec-12 19-Nov-13 07-Jul-14 31-Jan-16 25-Jul-17 24-Aug-18 01-Mar-19 28-Aug-06 19-Dec-22 16-Oct-16Switzerland 27-Feb-11 22-Dec-12 19-Nov-13 27-Jun-14 31-Jan-16 25-Jul-17 23-Aug-18 05-May-19 25-Jul-06 27-Feb-23 15-Oct-16Turkey 21-Oct-22United Kingdom 27-Feb-11 22-Dec-12 19-Nov-13 12-Dec-15 27-Jun-14 31-Jan-16 25-Jul-17 23-Aug-18 01-Mar-19 28-Aug-06 15-Oct-16

= molecule patent date Information provided by Foster City Intellectual Property 12th May 2010

= SPC date granted Only molecule patent data given: formulation patents may provide further protection

= SPC pending molecule patent date= SPC rejected/abandoned molecule patent date= Marketing / data exclusivity Combination products conservatively taken to be protected only for as long as the latest patent expiry of component molecules

HIV

SPC = Supplementary Protection Certificate, granted at discretion of individual countries to compensate for time taken to obtain marketing authorisation

DEFINIZIONE DI MEDICINALE GENERICO

Un medicinale che ha la stessa composizione

qualitativa e quantitativa di sostanze attive e la

stessa forma farmaceutica del medicinale di

riferimento nonché una bioequivalenza con il

medicinale di riferimento dimostrata da studi

appropriati di biodisponibilità

art. 10, comma 5 DLvo n. 219/06;art. 10, comma 2 Direttiva europea 2001/83/CE

e successive modificazioni.

Legge n. 425 del 8 agosto 1996 Art. 1 comma 3

II medicinale generico è un medicinale a base di uno o più principi attivi, prodotto industrialmente, non protetto da brevetto, identificato dalla denominazione comune internazionale (DCI) del principio attivo o, in mancanza di questa, dalla denominazione scientifica del medicinale, seguita dal nome del titolare dell'AIC, che sia bioequivalente rispetto ad una specialità medicinale già autorizzata con la stessa composizione quali-quantitativa in principi attivi, la stessa forma farmaceutica e le stesse indicazioni terapeutiche.

I Farmaci equivalenti in ItaliaDefinizione e normativa

Bioequivalenza

Due medicinali si definiscono bioequivalenti se contengono lo stesso principio attivo e, se dopo la somministrazione della stessa dose in identiche condizioni, i loro profili di concentrazione/tempo (biodisponibilità) sono così simili (da -20% a +25%) da non comportare differenze significative in termini di efficacia e sicurezza. Possono variare gli eccipienti e/o la dissoluzione e l’assorbimento.

Equivalenza terapeutica

Un medicinale è terapeuticamente equivalente di un altro, se contiene lo stesso principio attivo e clinicamente dimostra la stessa efficacia e sicurezza del prodotto di riferimento la cui efficacia e sicurezza sono già state documentate con studi appropriati.

In pratica, si accetta che uno studio di bioequivalenza sulla base dei profili plasmatici possa costituire la dimostrazione indiretta dell’equivalenza terapeutica di due farmaci che sono farmaceuticamente equivalenti o alternative farmaceutiche.

Farmaci Equivalenti

Stesso principio attivo del farmaco di riferimento

Stesso principio attivo del farmaco di riferimento

Non protetto da brevettoNon protetto da brevetto

Stessa composizione quali-quantitativa in

principio attivo

Stessa composizione quali-quantitativa in

principio attivo

rispetto al farmaco di riferimento

Bioequivalente rispetto al farmaco di riferimento

Bioequivalente

Stessa forma farmaceuticaStessa forma farmaceutica

Identificato dalla DCI del principio attivo

seguita dal nome del titolare AIC

Bromazepamratiopharm

Identificato dalla DCI del principio attivo

seguita dal nome del titolare AIC

Bromazepamratiopharm

Stesse indicazioniStesse indicazioni

Prezzo inferiore rispetto al farmaco di

riferimento

Prezzo inferiore rispetto al farmaco di

riferimento

GENERIC EQUIVALENCE

PhysicochemicalEquivalence

BiochemicalEquivalence

ClinicalEquivalence

PharmacologicEquivalence

Passato

Presente

Futuro??

HAART

Poor adherence and viral Poor adherence and viral rebound in suppressed patientsrebound in suppressed patients

Antinori, Antivir Ther 2004

Yasuda JM, Antivir Ther 2004

Paterson D. Ann Intern Med 2000

0

10

20

30

40

50

60

70

80

90

<70 70-80 80-90 90-95 >95

Adherence (% )

Perc

en

t V

L<4

00

co

pie

s/m

lLivelli di aderenza necessari per mantenere il successo virologico

Cosa preferisce il paziente?

Impact of number of pills per day on dose frequency preference

Patients were asked if they had to take a certain number of pills each day how would they prefer them to be administered

Moyle G et al. 6th ICDTHI, Glasgow, UK, 17-22 November 2002. Poster 99

N=504 across Europe

00

1010

2020

3030

4040

5050

6060

7070

8080

9090

100100 All at onceAll at once

Divided and taken twice-a-dayDivided and taken twice-a-day

Per

cen

t p

atie

nts

pre

ferr

ing

Per

cen

t p

atie

nts

pre

ferr

ing

>8 pills>8 pills 8 pills8 pills 6 pills6 pills 4 pills4 pills 3 pills3 pills

3131

6969

3838

6262 5959

4141

8484

1616

9393

77

Claxton AJ, et al. Clin Ther. 2001;23:1296-1310.

Mea

n D

os

e-T

aki

ng

A

dh

eren

ce

(%)

Studies of electronic monitoring of adherence

71

0

20

40

80

100

Overall

79

QD

69

BID

65

TID

51

QID

59

Overall

74

QD

58

BID

46

TID

40

QID

Dose-Timing Adherence RatesDose-Taking Adherence Rates

P values not calculated

60

P = .008

P < .001

P = .001

Adherence Is Inversely Related to the Number of Doses Per Day

Dose-taking adherence: appropriate number of doses taken during the day (optimal adherence variously defined as 70%, 80%, 90%)

Dose-timing adherence: doses taken at appropriate time intervals, within 25% of the dosing interval (eg, BID should be taken 12 3 hours apart)

87

7477

49

0

10

20

30

40

50

60

70

80

90

100

AI455135: Patient Adherence to QD vs More Frequent Therapy

• AI455135: 320 patients with HIV-1 RNA < 50 copies/mL for ≥ 90 days on BID (or more frequent) HAART (BID+)

• Randomized to switch to QD (d4T XR + 3TC + EFV) or continue BID+

• Week 48 virologic suppression noninferior with QD regimen

– QD: 80.0%

– BID+: 75.8%

• Adherence monitored

– ACTG Adherence Questionnaire

– MEMS caps

– Pill counts Boyle BA, et al. HIV Clin Trials. 2008;9:164-176.

% Taken % Taken on Time*

QDBID+

*Taken within 3 hours of prescribed interval.

Week 48 Adherence by MEMS Caps

Pati

en

ts A

ch

ievin

gC

om

plian

ce(%

)

P < .01

P < .01

Once-Daily vs Twice-Daily HAART in a Clinical Setting

Retrospective study of 218 patients on QD or BID antiretroviral therapy in an urban clinic (USA)

Munsiff A, et al. IAS 2005. Abstract WePe12.2C14.

OutcomeQD

(n = 78)BID

(n = 140)P Value

Median in HIV-1 RNA (c/mL) 1.9 0.7 .002

HIV-1 RNA < 400 c/mL, % 74 59 .027

HIV-1 RNA < 50 c/mL, % 68 45 .001

Virologic rebound, % 19 49 .014

Adherence (≥ 95%), % 83 63 .002

Months

Time to rebound among patients with virologic suppression

Pro

po

rtio

n R

emai

nin

gS

up

pre

ssed

QD group

BID group

P = .028

1.00

0.75

0.50

0.25

0.00

0 5 10 15 20 25 30

Incidenza cruda di VR x 100 PYFU

(95%CI)

1,6

4,7

6,47,3

11,1

0

2

4

6

8

10

12

14

QD BID 2-5 BID 6-8 BID 9-12 BID >12

Incidenza globale di VR: 6.2 X 100 PYFU (IC95% 5.6-7.0)

Ammassari A et al. CROI 2007

I C ONA

ItalianCohort

NaiveAntiretroviral

Strategie di semplificazione e aderenza: studi di coorte

• N° di pazienti: 3974• Follow-up totale: 4998 PYFU• VR: 311

Association Between ARV Pill Burden and Hospitalization

Nu

mb

er o

f H

osp

ital

izat

ion

s p

er 1

00 P

atie

nts

Nu

mb

er o

f H

osp

ital

izat

ion

s p

er 1

00 P

atie

nts

ART Naïve Patients ART Experienced Patients

Diff: -14.1; P<0.001 Diff: -14.3; P<0.001

Conclusion: Patients on a single tablet per day regimen had consistently lower hospitalization risk than those on other regimens.

2+ Pills Per Day Regimen

Single Tablet Per Day Regimen

2+ Pills Per Day Regimen

Single Tablet Per Day Regimen

Cohen C, et al. 51st ICAAC; Chicago, IL; Sept 17-20, 2011. Abst. H2-791.

Adherence levels are shown as a solid line and HIV-1 RNA levels as a dashed line. The dotted line represents optimal HIV viral suppression. PNP, patient non persistence

The relationship between patient persistence, regimen persistence, and adherence

JW Bae, 2011

24

Switching to Atripla (EFV/FTC/TDF) from its components leads to improved treatment satisfaction:

Results from the ONCE study

Cooper V, et al. EACS 2011;Belgrade. Poster PE7.5/6

Participants expressed a preference for Atripla over its components at 48 Wks (n=98)

Muchbetter

Slightlybetter

Aboutthe same

Slightlyworse

Muchworse

How does your current regimen compare to the previous HAART regimen your doctor prescribed for your HIV infection?

67(68.4%)

8(8.2%)

22(22.4%)

01

(1.0%)

Participants reported less treatment intrusiveness 48 weeks after switching to Atripla

The proportion of people who reported their HAART regimen was “very easy” to follow increased after

switching to Atripla

IQR1.10, 1.80

N=114 IQR1.00, 1.55

N=97

1

1.25

1.5

1.75

Baseline Week 48

Med

ian

HIS

sco

re

0

20

40

60

80

100

Baseline Week 48

1.4 1.2 70.2 91.8

P = 0.006*P < 0.0001*

*Wilcoxon signed rank test, n=97 *McNemar’s test, n=97

Perc

enta

ge (%

)

Adverse events after fixed-dose combinations of antiretrovirals

disruption

Francesc Homar1, Juan Martínez-Gómez1, Antonio Pareja2, Joaquín Serrano3,

Carmen Carratalá1, Antoni Payeras1.

1. Departments of Internal Medicine, 2. Epidemiology 3. Pharmacy

Hospital Son Llàtzer. Palma de Mallorca, Spain

EACS 2011 Belgrado

Methods

The aim of this study was to describe adverse events in patients exposed to FDCAs disruption in a single center

• We retrospectively compared adverse events reported by 75 patients exposed to FDCAs disruption and 150 non-exposed patients, matched by gender and type of FDCA, who did not changed the treatment

• We collected adverse events at visit-1 (before FDCA disruption), baseline (at the time of FDCA disruption) and at the next two follow-up visits (visit+1 and visit+2)

Homar F, et al. EACS 2011;Belgrade. Poster

Results:FDCA distribution of the exposed cohort

• Median time (range) on treatment with FDCAs and EFV was 20 months (1–119) and 48.5 months (1–127) respectively, with no statistical differences between groups.

• Both cohorts were comparable at baseline in sex, age, HIV risk factors, HCV co-infection, previous history of AIDS, history of psychiatric conditions, use of methadone or psychotropic drugs, CD4 cell count and HIV-RNA levels.

• FDCAs were disrupted for a median time of 3 months.

Atripla

Truvada

Kivexa

Combivir

Trizivir

29%

49%

11%

8%

3%

FDCAs that were disrupted in the exposed cohort

Homar F, et al. EACS 2011;Belgrade. Poster

Results: patient disposition

Exposed cohort(FDCAs

disruptioncohort)

Non-exposedcohort

(FDCAs cohort)

75 patients• Remain FDCAs disruption,

n=21• FDCAs resumed, n=47• Treatment change, n=6• Treatment

discontinuation, n=1

150 patients• Remain FDCAs, n=146• Treatment change, n=4• Treatment

discontinuation, n=0

Visit +1(month 2)

21 patients• Remain FDCAs disruption,

n=9• FDCAs resumed, n=10• Treatment change, n=0

Treatment discontinuation, n=0

• Missing n=2

146 patients• Remain FDCAs, n=132• Treatment change, n=2• Treatment

discontinuation, n=0• Missing, n=12

Visit +2(month 4)

Homar F, et al. EACS 2011;Belgrade. Poster

Adverse events (AEs)

• At visit+1, 21 out of 75 exposed patients vs 7 out of 150 non-exposed patients experienced AEs (OR 8; 95%CI 3.3-20.1, p=0.0000).

• Neuropsychiatric disorders related to efavirenz was the main AE reported (9 patients out of 14).

• At visit+2, 2.7% of the exposed patients experienced probably HAART-related AE vs 1.3% of the non-exposed group, being this difference non statistically significant.

Adverse eventsDescription of probably HAART-related AEs in the exposed group at visit +1

AE severity

Patients(N)

AE(N)

Mild Moderate Severe

Neuropsychiatric events 9 24 4 12 8

Toxic hepatitis 2 2 0 0 2

Diarrhea 2 2 1 1 0

Vomiting 1 1 0 1 0

Homar F, et al. EACS 2011;Belgrade. Poster

Severe adverse events probably relatedto HAART

• Four patients experienced a total 10 severe AEs in the exposed group: – toxic hepatitis (n=2), – insomnia (n=2), – abnormal dreams (n=1), – anxiety (n=1), – nervousness (n=1) – concentration difficulties (n=2)– hallucinations (n=1).

• No cases of severe HAART-related AEs were found in the non-exposed cohort

Adverse eventsPatients with probably HAART-related AEs by study visit

Exposed No exposed OR

Visit -14 / 75(5.3%)

1 / 150(0.7%)

n.s.

Baseline2 / 75(2.7%)

1 / 150(0.7%)

n.s.

Visit +114 / 75(18.7%)

2 / 150(1.3%)

OR 16.8; 95% CI 3.7–76.9)(p = 0.0000)

Visit +22 / 75(2.7%)

2 / 150(1.3%)

n.s.

Homar F, et al. EACS 2011;Belgrade. Poster

HIV RNA and CD4 cell count changes

• There were no statistically significant differences in the rate of patients with HIV RNA>50 cop/mL at visit +1(7% of the exposed patient vs. 9% in the non-exposed group) and visit +2 (13% vs 8%)

• No significant differences were found in changes from baseline in CD4 cell count

34

Cost analysis

• A post-hoc analysis was performed to calculate the implication in health care expenditures with this measure during 120 days (median of time with disrupted FDCA treatment)

• When considering only the management of HAART-related AEs, an incremental cost of 148 €/patient (1.24 €/patient/day) was observed

• When the cost of anticipating the follow-up visits is included in the analysis, the final cost increment reaches 494 €/patient (4.13 €/patient/day)

35

Conclusions

• In comparison with maintaining FDCAs, their disruption to include g3TC in the regimens were associated with higher risk of adverse events

• Many of these adverse events were neuropsychiatric disorders probably related to efavirenz in stable patients previously tolerating this drug

• Some of these adverse events were severe in intensity

• Unlike the desired objective of cost-saving, FDCAs disruption led to an increase of health care expenditure

154 Patients taking Atripla for at least three months with an undetectable viral load were asked to complete an anonymous survey

The majority of patients expressed an unwillingness to switch from Atripla and an individualized approach to such a strategy would appear to be needed

AIDS 2011, 25:1683–169

The fixed-dose antiretroviral coformulations (FDACs) represent a significant advance in the simplification of antiretroviral therapy, facilitating adherence to complex and chronic treatments, and contributing to a quantifiable improvement in patient quality of life.

AIDS 2011, 25:1683–169

These drug coformulations reduce the risk of treatment error, are associated with a lower risk of hospitalization, and can lessen the possibility of covert monotherapy in situations of selective noncompliance.

AIDS 2011, 25:1683–169

With the exception of those cases requiringdose adjustments, the preferential use of FDACs should be recommended for thetreatment of HIV-1 infection in those situations when the agents included in thecoformulation are drugs of choice.

L’uso di STR di per sé può essere un elemento chiave per contribuire a migliorare la qualità di vita e l’aderenza dei pazienti[AII]