Massimo Andreoni Azienda Ospedaliera Universitaria Policlinico Tor Vergata, Roma
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Transcript of Massimo Andreoni Azienda Ospedaliera Universitaria Policlinico Tor Vergata, Roma
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]