Riflessioni su STR
nella prospettiva
dei farmaci
generici in HIV
Massimo Andreoni
Azienda Ospedaliera Universitaria
Policlinico Tor Vergata, Roma
Registrational Treatment-Naive Clinical Trials:
Cross-Study Comparison*
HIV RNA <50 c/mL at Week 48
GS-103 QUAD (n=353)12
GS-102 QUAD (n=348)11
GS-103 ATV+RTV (n=355)12
STARTMRK RAL (n=281)8
GS-102 Atripla (n=352)11
ARTEMIS DRV+RTV (n=343)7
ECHO/THRIVE RPV (n=550)10
ECHO/THRIVE EFV (n=546)10
STARTMRK EFV (n=282)8
GS 934 EFV (n=244)4
ARTEMIS LPV/r (n=346)7
CASTLE ATV+RTV (n=440)6
ABT 730 LPV/r qd (n=333)5
CASTLE LPV/r (n=443)6
ABT 730 LPV/r bid (n=331)5
GS-903 EFV (n=299)9
KLEAN FPV/r (n=434)14
KLEAN LPV/r (n=444)14
GS 934 EFV (n=243)4
CNA 30024 EFV (n=324)13
CNA 30024 EFV (n=325)13
SOLO FPV/r (n=322)2
MERIT ES MVC (n=311)3
MERIT ES EFV (n=303)3
SOLO NFV (n=327)2
CNA 30021 EFV (n=386)1
CNA 30021 EFV (n=384)1
0
73
71
70
70
69
69
68
68
68
68
66
10
20
30
40
50
60
70
90
88
87
86
84
84
83
82
82
80
78
78
77
76
NRTI backbone
76
FTC/TDF
76
3TC/ABC qd
3TC+ABC bid
3TC/ZDV
3TC+TDF
80
90
% 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
100
STR: Strategie per ogni fase della terapia
Naive
Switch per tossicità
NNRTI
NNRTI Eviplera
PI DRV/cob/FTC/7340
NI QUAD - DLT/ABC/3TC
Atripla
PI
DRV/cob/FTC/7340
NI
QUAD
NNRTI Atripla
NNRTI Eviplera
NI QUAD
NNRTI Atripla
NNRTI Eviplera
PI DRV/cob/FTC/7340
NI DLT/ABC/3TC
STR: Strategie per ogni fase della terapia
Naive
Switch per fallimento
NNRTI
PI DRV/cob/FTC/7340
NI QUAD – DLT/ABC/3TC
Atripla
PI
DRV/cob/FTC/7340
NI
QUAD
NNRTI Atripla
NNRTI Eviplera
NI QUAD – DLT/ABC/3TC
NNRTI Atripla
NNRTI Eviplera
PI DRV/cob/FTC/7340
NI DLT/ABC/3TC ?
EU Patent Expiry Dates
HIV
Typical core 5 EU Patent
Expiry Date
Albania
Australia
Austria
Belgium
Bulgaria
Croatia
Cyprus
Czech Republic
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Israel
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Monaco
Netherlands
New Zealand
Norway
Poland
Portugal
Romania
Russia
Slovakia
Slovenia
Spain
Sweden
Switzerland
Turkey
United Kingdom
Epivir
Viramune
Sustiva
Lamivudine
Nevirapine
Efavirenz
08-Aug-11
23-Dec-12
20-Nov-13
Dec-13
13-Mar-11
28-Feb-11
28-Feb-11
None
07-May-12
05-Feb-13
05-Feb-13
06-Aug-13
20-Nov-13
20-Nov-13
30-Jan-15
07-Aug-13
16-Dec-13
16-Dec-13
13-Dec-15
None
14-Jul-13
27-Dec-11
08-Aug-11
None
07-Aug-11
08-Aug-11
08-Aug-11
08-Feb-10
None
27-Feb-11
08-Feb-10
08-Aug-11
28-Feb-11
23-Dec-12
02-Feb-15
20-Nov-13
23-Dec-12
23-Dec-12
23-Dec-12
23-Dec-12
04-Sep-11
20-Nov-13
20-Nov-13
20-Nov-13
19-Nov-13
07-Aug-13
04-Feb-13
19-Nov-13
07-Aug-13
20-Nov-13
Kaletra
Lopinavir /
ritonavir
None
None
29-Dec-13
None
15-Dec-13
17-Dec-13
15-Dec-15
21-Dec-13
None
None
14-Dec-15
None
Ziagen
Emtriva
Abacavir
Emtricitabine
28-Jun-14
31-Jan-16
28-Jun-14
28-Jun-14
31-Jan-16
31-Jan-16
31-Jan-16
24-Jul-17
09-Dec-19
21-Dec-10
28-Jun-14
20-Feb-17
31-Jan-16
27-Jun-14
28-Jun-14
28-Jun-14
29-Jun-14
21-Dec-10
20-Feb-17
31-Jan-16
31-Jan-16
01-Feb-16
31-Jan-16
27-Jun-14
22-Dec-10
09-Jul-14
26-Jun-14
31-Jan-16
HBV
Viread
Tenofovir
Disoproxil
Norvir
Isentress
Baraclude
Darunavir Atazanavir
Ritonavir
Raltegravir
Entecavir
25-Jul-17
23-Aug-18 02-Mar-19
Dec-13
20-Dec-22
16-Oct-16
None
25-Jul-17
25-Jul-17
25-Jul-17
None
24-Aug-13 12-Jan-19
Pending 03-Mar-19
24-Aug-18 03-Mar-19
02-Mar-19
16-Dec-13
16-Dec-13
28-Aug-06
28-Aug-06
28-Aug-06
28-Aug-06
28-Aug-06
29-Dec-13
28-Aug-06
28-Aug-06
28-Aug-06
17-Dec-13
15-Dec-15
21-Dec-13
None
15-Dec-13
21-Oct-22
21-Oct-22
02-Jan-23
20-Dec-22
04-Oct-16
16-Oct-16
16-Oct-16
None
21-Oct-22
20-Dec-22
20-Dec-22
20-Dec-22
21-Oct-22
20-Dec-22
22-Oct-22
21-Dec-22
21-Oct-22
19-Dec-22
19-Dec-22
None
None
16-Oct-16
None
18-Oct-16
15-Oct-16
17-Oct-11
17-Oct-16
17-Oct-16
None
30-Sep-16
20-Dec-22
20-Dec-22
21-Oct-22
21-Dec-22
02-Jan-23
16-Oct-16
None
16-Oct-11
None
16-Oct-16
19-Dec-22
21-Oct-22
21-Oct-22
16-Oct-11
01-Oct-11
17-Oct-16
18-Oct-11
14-Jan-19
18-Oct-15
20-Dec-22
20-Dec-22
20-Dec-22
19-Dec-22
27-Feb-23
21-Oct-22
None
None
25-Jul-17
None
25-Jul-17
25-Jul-17
25-Jul-17
25-Jul-17
None
None
25-Jul-17
25-Jul-17
None
Prezista
Reyataz
22-Apr-17
24-Aug-18 02-Mar-19
12-Feb-18
23-Aug-18
12-Feb-18
Pending
02-Mar-19
02-Mar-19
22-Apr-17
08-May-19
Pending
24-Aug-18 02-Mar-19
28-Aug-06
28-Aug-06
23-Dec-12
None
08-Aug-11
None
07-Aug-11
08-Feb-10
28-Feb-11
08-Feb-10
08-Feb-10
05-Feb-13
20-Nov-13
22-Dec-12
16-Nov-10
23-Dec-12
20-Nov-13
06-Aug-13
20-Nov-13
06-Aug-13
21-Nov-13
09-Jan-15
None
None
None
28-Jun-14
31-Jan-16
19-Mar-16
07-Jul-14
31-Jan-16
12-Dec-15
None
15-Dec-15
06-May-12
27-Dec-11
28-Feb-11
08-Feb-10
07-Aug-11
27-Feb-11
27-Feb-11
05-Feb-13
22-Dec-12
22-Dec-12
20-Mar-15
20-Nov-13
20-Nov-13
19-Nov-13
19-Nov-13
None
None
20-Mar-16
22-Dec-12
19-Nov-13
12-Dec-15
= molecule patent date
= SPC date granted
= SPC pending  molecule patent date
= SPC rejected/abandoned  molecule patent date
= Marketing / data exclusivity
None
25-Jul-17
None
25-Jul-17
25-Jul-17
25-Jul-17
02-Mar-19
31-Jan-16
20-Feb-17
31-Jan-16
01-Jan-17
None
25-Jul-17
01-Jan-17
22-Apr-17
22-Apr-17
25-Aug-18 03-Mar-19
Pending
28-Aug-06
None
None
28-Aug-06
16-Dec-13
28-Aug-06
08-Jul-14
07-Jul-14
27-Jun-14
25-Jul-17
02-Aug-15
31-Jan-11
31-Jan-16
31-Jan-16
None
None
25-Jul-17
25-Jul-17
25-Jul-17
22-Apr-17
02-Mar-19
24-Aug-18 02-Mar-19
24-Aug-18 01-Mar-19
23-Aug-18 05-May-19
28-Aug-06
28-Aug-06
20-Mar-16
28-Aug-06
25-Jul-06
27-Jun-14
31-Jan-16
25-Jul-17
23-Aug-18 01-Mar-19
28-Aug-06
Pending
10-Oct-16
28-Jun-14
04-Jun-12
10-Nov-15
Pending
01-Mar-19
28-Aug-06
28-Aug-06
28-Aug-06
03-Jul-18
21-Dec-22
21-Dec-22
None
None
16-Oct-16
16-Oct-16
15-Oct-16
15-Oct-16
Information provided by Foster City Intellectual Property 12th May 2010
Only molecule patent data given: formulation patents may provide further protection
SPC = Supplementary Protection Certificate, granted at discretion of individual countries to compensate for time taken to obtain marketing
authorisation
Combination products conservatively taken to be protected only for as long as the latest patent expiry of component molecules
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.
I Farmaci equivalenti in Italia
Definizione e normativa
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.
Legge n. 425 del 8 agosto 1996 Art. 1 comma 3
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
Non protetto da brevetto
Stesso principio attivo
del farmaco di riferimento
Stessa composizione
quali-quantitativa in
principio attivo
Stesse indicazioni
Stessa forma farmaceutica
Prezzo inferiore
rispetto al farmaco di
riferimento
Identificato
dalla DCI del principio attivo
seguita dal nome del titolare AIC
Bioequivalente
Bromazepam ratiopharm
rispetto al
farmaco di
riferimento
Physicochemical
Equivalence
Biochemical
Equivalence
GENERIC EQUIVALENCE
Pharmacologic
Equivalence
Clinical
Equivalence
Passato
HAART
Presente
Futuro??
Poor adherence and viral rebound in
suppressed patients
Antinori, Antivir Ther 2004
Yasuda JM, Antivir Ther 2004
Livelli di aderenza necessari per
mantenere il successo virologico
90
Percent VL<400
copies/ml
80
70
60
50
40
30
20
10
0
<70
70-80
80-90
90-95
>95
Adherence (%)
Paterson D. Ann Intern Med 2000
Cosa preferisce il
paziente?
Percent patients preferring
Impact of number of pills per day
on dose frequency preference
100
90
All at once
Divided and taken twice-a-day
80
N=504 across Europe
93
84
70
69
60
62
50
40
30
20
59
41
38
31
10
16
7
4 pills
3 pills
0
>8 pills
8 pills
6 pills
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
Adherence Is Inversely Related to the
Number of Doses Per Day
Dose-Taking Adherence Rates
P < .001
P = .008
Mean Dose-Taking
Adherence (%)
100
Dose-Timing Adherence Rates
P values not calculated
P = .001
80
60
71
79
69
74
65
51
40
59
58
46
40
TID
QID
20
0
Overall
QD
BID
TID
QID
Overall QD
BID
Studies of electronic monitoring of adherence

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)
Claxton AJ, et al. Clin Ther. 2001;23:1296-1310.
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
Week 48 Adherence by MEMS Caps
100
Patients Achieving
Compliance(%)
•
90
80
QD
BID+
P < .01
87
77
70
60
74
P < .01
49
50
40
30
20
10
0
% Taken
% Taken on
Time*
–
ACTG Adherence Questionnaire
–
MEMS caps
*Taken within 3 hours of prescribed interval.
–
Pill counts
Boyle BA, et al. HIV Clin Trials. 2008;9:164-176.
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)
QD
(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
Outcome
Time to rebound among patients with virologic suppression
Proportion Remaining
Suppressed

1.00
P = .028
QD group
0.75
0.50
BID group
0.25
0.00
0
5
10
Munsiff A, et al. IAS 2005. Abstract WePe12.2C14.
15
Months
20
25
30
Italian
Cohort
I CO
NA
Naive
Antiretroviral
14
12
Strategie di semplificazione e
aderenza: studi di coorte
•
•
•
N° di pazienti: 3974
Follow-up totale: 4998 PYFU
VR: 311
Incidenza globale di VR: 6.2 X 100
PYFU (IC95% 5.6-7.0)
11,1
10
Incidenza 8
cruda di VR
x 100 PYFU
(95%CI) 6
6,4
4,7
4
2
0
7,3
1,6
QD
BID 2-5
BID 6-8
BID 9-12
BID >12
Ammassari A et al. CROI 2007
ART Naïve Patients
Diff: -14.1; P<0.001
Single Tablet Per
Day Regimen
2+ Pills Per
Day Regimen
Number of Hospitalizations per 100 Patients
Number of Hospitalizations per 100 Patients
Association Between ARV Pill Burden
and Hospitalization
ART Experienced Patients
Diff: -14.3; P<0.001
Single Tablet Per
Day Regimen
2+ Pills Per
Day Regimen
Conclusion: Patients on a single tablet per day regimen had consistently lower hospitalization risk
than those on other regimens.
Cohen C, et al. 51st ICAAC; Chicago, IL; Sept 17-20, 2011. Abst. H2-791.
The relationship between patient persistence,
regimen persistence, and adherence
JW Bae, 2011
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
Switching to Atripla (EFV/FTC/TDF) from its components
leads to improved treatment satisfaction:
Results from the ONCE study
Participants reported less treatment
intrusiveness 48 weeks after switching to Atripla
1.5
P = 0.006*
IQR
1.10, 1.80
N=114
1.25
P < 0.0001*
100
IQR
1.00, 1.55
N=97
1.4
1.2
Baseline
Week 48
Percentage (%)
Median HIS score
1.75
The proportion of people who reported their HAART
regimen was “very easy” to follow increased after
switching to Atripla
80
60
40
20
0
1
*Wilcoxon signed rank test, n=97
70.2
91.8
Baseline
Week 48
*McNemar’s test, n=97
Participants expressed a preference for
Atripla over its components at 48 Wks (n=98)
Much
better
Slightly
better
About
the same
Slightly
worse
Much
worse
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%)
0
1
(1.0%)
24
Cooper V, et al. EACS 2011;Belgrade. Poster PE7.5/6
Adverse events after fixed-dose
combinations of antiretrovirals
disruption
EACS 2011 Belgrado
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
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 nonexposed 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
FDCAs that were disrupted in the exposed cohort
29%
11%
8%
49%
3%
Atripla
Truvada
Kivexa
Combivir
Trizivir
• 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.
Homar F, et al. EACS 2011;Belgrade. Poster
Results: patient disposition
Visit +1
(month 2)
Visit +2
(month 4)
Exposed cohort
(FDCAs
disruption
cohort)
75 patients
• Remain FDCAs disruption,
n=21
• FDCAs resumed, n=47
• Treatment change, n=6
• Treatment
discontinuation, n=1
21 patients
• Remain FDCAs disruption,
n=9
• FDCAs resumed, n=10
• Treatment change, n=0
Treatment
discontinuation, n=0
• Missing n=2
Non-exposed
cohort
(FDCAs cohort)
150 patients
• Remain FDCAs, n=146
• Treatment change, n=4
• Treatment
discontinuation, n=0
146 patients
• Remain FDCAs, n=132
• Treatment change, n=2
• Treatment
discontinuation, n=0
• Missing, n=12
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 events
Description 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 related
to 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 events
Patients with probably HAART-related AEs by study visit
Exposed
No exposed
OR
Visit -1
4 / 75
(5.3%)
1 / 150
(0.7%)
n.s.
Baseline
2 / 75
(2.7%)
1 / 150
(0.7%)
n.s.
Visit +1
14 / 75
(18.7%)
2 / 150
(1.3%)
OR 16.8; 95% CI 3.7–76.9)
(p = 0.0000)
Visit +2
2 / 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
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 HAARTrelated 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)
34
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
35
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
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 requiring
dose adjustments, the preferential use of
FDACs should be recommended for the
treatment of HIV-1 infection in those
situations when the agents included in the
coformulation are drugs of choice.
AIDS 2011, 25:1683–169
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]