Our Current ARVS
The Nucleoside/
Nucleotide Reverse Transcriptase Inhibitors (NRTIs/ NtRTIs)
The Non-Nucleoside Reverse Transcriptase
Inhibitors (NNRTIs)
The Protease Inhibitors
(PIs)
AbacavirEmtricitabineLamivudineStavudineTenofovir
Zidovudine
EfavirenzNevirapine
AtazanavirDarunavirLopinavirRitonavir
Fixed-drug combinations
Combivir, Kivexa, Truvada
Triomune, Atripla, Triplavar
ARVS REGISTSERED IN SOUTH AFRICA
The Nucleoside/
Nucleotide Reverse Transcriptase Inhibitors (NRTIs/ NtRTIs)
The Non-Nucleoside Reverse Transcriptase
Inhibitors (NNRTIs)
The Protease Inhibitors
(PIs)
AbacavirDidanosine
EmtricitabineLamivudineStavudineTenofovir
Zidovudine
EfavirenzNevirapineEtravirineRilpivirine Amprenavir
AtazanavirDarunavirIndinavirLopinavirRitonavir
Saquinavir
The Integrase Inhibitors (ISTIs)
Raltegravir Fixed-drug combinations
Combivir, Kivexa, Truvada
Triomune, Atripla, Tripalvar, Complera
THE ANTIRETROVIRAL DRUGS
The Nucleoside/
Nucleotide Reverse Transcriptase Inhibitors (NRTIs/ NtRTIs)
The Non-Nucleoside Reverse Transcriptase
Inhibitors (NNRTIs)
The Protease Inhibitors
(PIs)
AbacavirDidanosine
EmtricitabineLamivudineStavudineTenofovir
Zidovudine
EfavirenzNevirapineEtravirineRilpivirine
AmprenavirAtazanavirDarunavirIndinavirLopinavirRitonavir
Saquinavir Tipranavir
The Integrase Inhibitors (ISTIs)
Raltegravir ElvitegravirDolutegravir
Fixed-drug combinations
Combivir, Kivexa, Truvada
Triomune, Atripla, Complera
The QUAD
Drugs to be covered
• Etravirine• Rilpivirine• Raltegravir• Elvitegravir• Dolutegravir• Darunavir/r• Maraviroc
Etravirine
• Etravirine (ETV) is a second generation NNRTI that • ETV works like other NNRTIs by binding to the
catalytic site of the RT enzyme
• Active against HIV with K103N and Y181C
• This potency appears to be related to etravirine's flexibility as a molecule
• Dosage 200mg bd
Etravirine (2)
• Pivotal study DUET 1 and 2• OBR +darunavir/r +etravirine/placebo• After 24 weeks, pooled analysis - etravirine study arm
achieved an undetectable viral load (58.9% vs 41.1%; p<0.0001).
• There was also a significantly greater increase in CD4 cell count from baseline in the etravirine arm (86 vs 67 cells/mm3; p<0.006).
HIV-infected patients with virologic failure on current
HAART regimen, history of ≥ 1 NNRTI RAM,
≥ 3 primary PI mutations, and HIV-1 RNA > 5000 copies/mL
(DUET-1: N = 612;DUET-2: N = 591)
Placebo +Darunavir/Ritonavir-containing OBR*
(DUET-1: n = 308;DUET-2: n = 296)
Etravirine 200 mg BID +Darunavir/Ritonavir-containing OBR*
(DUET-1: n = 304;DUET-2: n = 295)
Week 48
*Investigator-selected OBR included darunavir/ritonavir 600/100 mg twice daily + ≥ 2 NRTIs ± enfuvirtide.
Week 24
Summary of Study DesignDUET 1 and 2
1. Madruga JV, et al. Lancet. 2007;370:29-38. 2. Lazzarin A, et al. Lancet. 2007;370:39-48.
Main Findings
• Significantly more patients achieved HIV-1 RNA < 50 copies/mL with etravirine vs placebo
• HIV-1 RNA reduction from baseline greater in etravirine arms than placebo arms
• Etravirine treatment resulted in greater CD4+ cell count increases from baseline compared with placebo (statistical significance reached in DUET-1 only)
Madruga JV, et al. Lancet. 2007;370:29-38. Lazzarin A, et al. Lancet. 2007;370:39-48.
• 13 RT mutations at eight positions were found to reduce ETV activity – V90I, A98G, L100I, K101E/P, V106I, V179D/F,
Y181C/I/V and G190A/S
Etravirine
FDC NOSingle day dosage NOLow side effect profile
YES High barrier to resistance
?TB friendly NOPregnancy friendly UNK
Rilpivirine 25 mg QD+ TDF/FTC 300/200 mg QD
(n = 346)
EFV 600 mg QD+ TDF/FTC 300/200 mg QD
(n = 344)
*THRIVE only. †Selected by investigator from ABC/3TC, TDF/FTC, ZDV/3TC.
Stratification by BL HIV-1 RNA < 100,000
vs ≥ 100,000 copies/mL, NRTI use*
Wk 96final analysis
Wk 48primary analysis
Rilpivirine 25 mg QD+ 2 NRTIs†
(n = 340)
EFV 600 mg QD+ 2 NRTIs†
(n = 338)
ECHO, THRIVE: Rilpivirine vs EFV in Treatment-Naive Patients
• Randomized, double-blind phase III trials
Cohen C, et al. AIDS 2010. Abstract THLBB206.
ECHO(N = 690)
THRIVE(N = 678)
Treatment-naive, HIV-1 RNA ≥ 5000 copies/mL
no NNRTI RAMs,susceptible to NRTIs
ECHO, THRIVE: Rilpivirine vs EFV in Treatment-Naive Patients
HIV-1 RNA < 50 copies/mL (ITT-TLOVR) at Wk 48
*P < .0001 for noninferiority at -12% margin.
Rilpivirine EFV
Cohen C, et al. AIDS 2010. Abstract THLBB206. Graphics used with permission.
HIV-1 RNA < 50 copies/mL at Wk 48 by BL VL
40
0
100
20
8082.384.3
60
682686n =
ECHO THRIVEPooled
Pa
tie
nts
(%
)
82.882.9 81.785.6
338340344346
-3.6 (-9.8 to +2.5)
6.6 (1.6-11.5)
> 100,000 copies/mL
125/165
121/153
246/318
149/181
136/171
285/352
7781 79 8076 82
Pa
tie
nts
(%
)
40
0
100
20
80
60
Pooled THRIVEECHO
≤100,000 copies/mL
162/181
170/187
332/368
136/163
140/167
276/330
9083
9184
9084
Pa
tie
nts
(%
)
40
0
100
20
80
60
ECHO THRIVEPooled
ECHO, THRIVE: Treatment Failure, Resistance, and Adverse Events
Wk 48 Outcome Rilpivirine(n = 686)
Efavirenz(n = 682)
VF with resistance data, n 62 28
No NNRTI or NRTI RAMs,% 29 43
1 Emergent NNRTI RAM,% 63 54
Most frequent NNRTI RAM E138K K103N
1 Emergent NRTI RAMs, % 68 32
Most frequent NRTI RAM M184I M184V
Cohen C, et al. AIDS 2010. Abstract THLBB206. Table used with permission.
Treatment Failure in ECHO and THRIVE
Adverse Events and Discontinuation
Resistance at Virologic Failure
6
0
15
3
12
94.8
346n =
VF
9.0
682686
6.7
AE
2.0
682686
Pat
ien
ts (
%)
Wk 48 Outcome, %
Rilpivirine(n = 686)
Efavirenz(n = 682)
P Value
DC for AE 3 8 .0005
Most Common AEs of Interest, %
Any neurologic AE 17 38 < .0001
Any psychiatric AE 15 23 .0002
Any rash 3 14 < .0001
Rilpivirine
EFV
Rilpivirine
FDC YESSingle day dosage YESLow side effect profile
YES High barrier to resistance
NOTB friendly NOPregnancy friendly UNK
Pommier Y, et al. Nat Rev Drug Discov. 2005;4:236-248.
HIV Replication Cycle and Drug Targets
a. Entry inhibitorsb. Reverse transcriptase inhibitorsc. Protease inhibitorsd. 3 -processing inhibitors′e. Strand transfer inhibitors
BENCHMRK-1 & -2: Patients With
HIV-1 RNA < 50 c/mL at Week 48
0 2
Pa
tie
nts
(%
)
60
40
0
Weeks
100
80
20
8 12 16 24 32 40 484
118 118 118 118 117 118 118232 231 231230 229 232 229
118230
118231
33%
62%*
31%
65%*
n =n =
0
36%
62%*
34%
60%*
119 119 118 119 119 119 119230 228 227 230 229 229 224
119228
119228
Pa
tie
nts
(%
)
60
40
100
80
20
0 2Weeks
8 12 16 24 32 40 484
*P < .001 for RAL vs placebo, derived from a logistic regression model adjusted for baseline HIV-1 RNA level (log10), first ENF use in OBR, first DRV use in OBR, active PI in OBR.
Placebo + OBR
RAL + OBRBENCHMRK-1[1] BENCHMRK-2[2]
1. Cooper DA, et al. CROI 2008. Abstract 788. 2. Steigbigel R, et al. CROI 2008. Abstract 789. Adapted with permission of Merck & Co., Inc., Whitehouse Station, New Jersey, USA, Copyright © 2008 Merck & Co., Inc. All Rights Reserved.
281279
• Phase III trial of EFV vs RAL, both with TDF/FTC in tx-naive patients
• At Wk 156, RAL noninferior to EFV (ITT, NC = F analysis)
STARTMRK: Efavirenz vs Raltegravir at 156 Wks in Antiretroviral-Naive Patients
CD4+ count : +332 (RAL) vs +295 (EFV)
Lazzarin A, et al. ICAAC 2011. Abstract H2-790.
HIV-1 RNA < 50 c/mL by Prespecified BL Characteristic*
Subgroup, n/N (%) RAL EFV
Male Female
172/194 (89)40/43 (93)
159/188 (85)33/39 (85)
BlackWhiteLatino
18/23 (78)83/94 (88)50/54 (93)
17/22 (77)82/90 (91)42/55 (76)
VL ≤ 100K VL > 100K
99/105 (94)113/132 (86)
93/111 (84)99/116 (85)
CD4 ≤ 50CD4 > 50 - ≤ 200CD4 > 200
16/23 (70)80/89 (90)
116/125 (93)
24/28 (86)68/84 (81)
100/115 (87)
HBV ± HCVNo coinfection
11/12 (92)201/225 (89)
11/13 (85)181/214 (85)
Age ≤ medianAge > median
109/124 (88)103/113 (91)
108/131 (82)84/96 (88)
*Study not powered for statistical significance for these comparisons.
100
80
60
40
20
0
HIV
-1 R
NA
< 5
0 c
/mL
(%
)
0 16 32 48 60 72 84 96 108120 132144 156
Wks
RALEFV
Patients at Risk, n
281282
278280
281282
280281
279281
281282
86
82
81
79
75
68
∆ (95% CI) = +7.3 (-0.2 to +14.7)Noninferiority P < .001
RALEFV
REALMRK: 48-Wk Efficacy of Raltegravir BID in Women, Blacks
• Multicenter, multinational, open-label, single-arm study to determine efficacy of RAL 400 mg BID (+ investigator-selected ARVs) in women, blacks—populations underrepresented in clinical trials
• Enrollment goals: 25% women (actual 47%), 50% black (actual 74%)• No difference in PK parameters by race or sex; no new RAL safety signals noted• Retention 84% throughout study; bolstered by strict selection criteria and retention initiatives
Male Female
Squires K, et al. ICAAC 2011. Abstract H2-789.
Black Nonblack
IntolerantFailure
0
20
40
60
80
100
HIV
-1 R
NA
< 50
cop
ies/
mL
at W
k 48
(%)
71.4
85.7
78.6 71.4 66.0 61.4 63.8 64.0
80.5
71.8 69.4
100Naive Previously Treated
10/14 6/7 11/14 5/7 27/44
33/50
44/69
16/25
33/41
28/39
43/62
18/18
• Multicenter, randomized, open-label phase II trial– Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 24
Antiretroviral-naive pts initiating rifampin-
containing therapy* for TB coinfection
(N = 154)
Raltegravir 400 mg BID +Tenofovir + Lamivudine
(n = 51)
Raltegravir 800 mg BID +Tenofovir + Lamivudine
(n = 51)
Efavirenz +Tenofovir + Lamivudine
(n = 52)
Wk 24Primary endpoint Wk 48
Raltegravir 400 mg BID +Tenofovir + Lamivudine
*Rifampin-containing therapy initiated before ART and consisted of rifampin, isoniazid, pyrazinamide, and ethambutol for 2 mos, followed by rifampin and isoniazid for 4 mos.
ANRS REFLATE: EFV- vs RAL-Based ART in HIV/TB-Coinfected Pts
Grinsztejn B, et al. AIDS 2012. Abstract THLBB01.
Virologic Failure at Wk 24
RAL 400 (n = 51)
RAL 800(n = 51)
EFV(n = 51)
VL > 50 c/mL, n (%) 12 (24) 4 (8) 15 (29)
REFLATE: Virologic Suppression at Wk 24 by ART Regimen
Grinsztejn B, et al. AIDS 2012. Abstract THLBB01. Graphic reproduced with permission.
RAL 400 mgRAL 800 mgEFV
100
80
60
40
20
0
Pts
wit
h V
L <
50
c/m
L (
%)
240 2 4 8 12 16 20
Wks
ITT; M = F, D/C = F
7876
67
Raltegravir
FDC NOSingle day dosage NOLow side effect profile
YES High barrier to resistance
NOTB friendly MAYBEPregnancy friendly UNK
Elvitegravir
• Intergrase inhibitors.• Requires boosting
– ritonavir – Cobicistat
• Co-formulated with a booster, TDF and FTC • QUAD-Stribild
Cobicistat: A New Boosting Agent• Small molecule with no HIV activity
– No concern of drug resistance in pts with suboptimal virologic response
• Similar from BL in fasting TC and TGs compared with RTV when boosting same agent[1]
• Inhibitor of CYP3A4; many drug–drug interactions[2,3]
• Modest, rapid increase in serum Cr due to inhibition of tubular secretion[3]
– Not associated with any change in actual GFR
– Other drugs (including ARVs) have similar effect[4,5]
• Availability of cobicistat has allowed for development of new coformulated agents and regimens
1. Gallant JE, et al. J Infect Dis. 2013;208:32-39. 2. DHHS Guidelines February 2013. 3. TDF/FTC/EVG/COBI [package insert]. 4. RPV [package insert]. 5. DTG [package insert].
Renal Monitoring With Cobicistat
9. TDF/FTC/EVG/COBI [package insert]. 10. DHHS Guidelines February 2013.
Wk 4—new baseline against which further changes should be measured
Ch
ang
e F
rom
BL
in
S
eru
m C
r(m
g/d
L;
IQR
)
0-0.05
-0.10
0.150.10
0.05
0.20
2 4 8 12 16 24 32 40 48Wks
BL
*Serum phosphorus should be measured in patients at risk for renal impairment
At BL,* Estimated CrCl Urine glucose Urine protein
Renal Monitoring With Cobicistat
• Coformulated drugs containing COBI should not be initiated in pts with estimated CrCl < 70 mL/min – Studies ongoing in pts with CrCl < 70
• Interpretation of changes in renal function may be problematic when using coformulations of COBI and TDF• TDF/FTC/EVG/COBI should not be used with other nephrotoxic drugs
12. TDF/FTC/EVG/COBI [package insert]. 13. DHHS Guidelines February 2013.
Serum Cr* Serum Cr*Serum Cr* Serum Cr*
UA UA
Ch
ang
e F
rom
BL
in
S
eru
m C
r(m
g/d
L;
IQR
)
0-0.05
-0.10
0.150.10
0.05
0.20
At BL,* Estimated CrCl Urine glucose Urine protein
Wk 4—new baseline against which further changes should be measured
2 4 8 12 16 24 32 40 48Wks
BL
*Serum phosphorus should be measured in patients at risk for renal impairment
Key Drug–Drug Interactions With COBI
• Antacids• Benzodiazepines• Beta-blockers• Calcium channel blockers• Erectile dysfunction drugs• Inhaled/injectable corticosteroids• MVC• OCPs (norgestimate)• Rifampin• Statins
14. DHHS Adult Guidelines. February 2013
Cobicistat—Status in EU and US
• In July 2013, EMEA approved cobicistat as a PK enhancer of atazanavir 300 mg once daily or darunavir 800 mg once daily as part of a complete ART regimen in adults
• In US, currently approved only as part of coformulated single-tablet regimen TDF/FTC/EVG/COBI– Approval as single agent pending
15. EMA.europa.eu. Assessment report on cobicistat. 16. FDA.gov. Approval of TDF/FTC/EVG/COBI.
Elvitegravir/Cobicistat vs EFV or ATV/RTV + TDF/FTC in Treatment-Naive Patients
• Randomized, double-blind, active-controlled phase III studies• Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48
17. Sax P, et al. Lancet. 2012;379:2439-2448. 18. DeJesus E, et al. Lancet. 2012;379:2429-2438.
Treatment naive HIV-1 RNA ≥ 5000 copies/mL
Any CD4+ cell countSusceptible to TDF, FTC, and EFV, or ATV
eGFR ≥ 70 mL/min
Study 102[17]
(N = 700)
Study 103[18]
(N = 708)
EVG/COBI/TDF/FTC QD(n = 348)
EFV/FTC/TDF QD(n = 352)
EVG/COBI/TDF/FTC QD(n = 353)
ATV/RTV + TDF/FTC QD(n = 355)
EVG/COBI/TDF/FTC Noninferior to EFV/TDF/FTC Through Wk 144
19. Sax PE, et al. Lancet. 2012;379:2439-2448. 20. Zolopa A, et al. J Acquir Immune Defic Syndr. 2013;63:96-100. 21. Wohl D, et al. ICAAC 2013. Abstract H-672a.
Wk 48
Wk 144
EVG/COBI/TDF/FTC (n = 348)
EFV/TDF/FTC (n = 352)
8075
0
20
40
60
80
100
Subj
ects
(%)
8884 84 82
Wk 96
7 7 6 8 7 104 5 5
7 6 7
Wk 48
Wk 144
Wk 96
Wk 48
Wk 144
Wk 96
Virologic Success* Virologic Failure D/c due to AEs
95% CI for Difference
Wk 48[1]
Wk 96[2]
Wk 144[3]
-12% 12%0
Favors EFV
Favors EVG/COBI
-1.3% 11.1%
4.9%
3.6%
8.8%
2.7%
-1.6%
-2.9%
*HIV-1 RNA < 50 copies/mL as defined by FDA Snapshot algorithm.
EVG/COBI/TDF/FTC Noninferior to ATV/RTV + TDF/FTC Through Wk 144
22. De Jesus E, et al. Lancet. 2012;379:2429-2438. 23. Rockstroh J, et al. J Acquir Immune Defic Syndr. 2013;62:483-486. 24. Clumeck N, et al. EACS 2013. Abstract LBPS7/2.
ATV/RTV + TDF/FTC (n = 355)
78 75
90 87
Wk 48
Wk 144
0
20
40
60
80
100
Wk 96
Wk 48
Wk 144
Wk 96
Wk 48
Wk 144
Wk 96
Virologic Success* Virologic Failure
83 82
5 5 47 7 78 5 4 6 6 8
-12% 12%0
Favors ATV/RTV
Favors EVG/COBI
*HIV-1 RNA < 50 copies/mL as defined by FDA Snapshot algorithm.
-3.2% 9.4%
3.1%
2.7%
7.5%1.1%
6.7%
-2.1%
-4.5%
Wk 48[22]
Wk 96[23]
Wk 144[24]
D/c due to AEs
95% CI for Difference
EVG/COBI/TDF/FTC (n = 353)
Subj
ects
(%)
QUAD
FDC YESSingle day dosage YESLow side effect profile
YES High barrier to resistance
YESTB friendly NOPregnancy friendly UNK
Dolutegravir
• Dolutegravir (DTG) is a newer, potent INSI with low nanomolar activity that is suitable for once-daily, unboosted dosing
• Furthermore, in vitro, DTG retains activity against most isolates carrying major integrase resistance mutations to RAL and/or EVG
Dolutegravir Phase III Trials in Treatment-Naive Patients
• Randomized, noninferiority phase III studies
• Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48
ART-naive ptsVL ≥ 1000 c/mL
(N = 822)
DTG 50 mg QD + 2 NRTIs*(n = 411)
RAL 400 mg BID + 2 NRTIs*(n = 411)
*Investigator-selected NRTI backbone: either TDF/FTC or ABC/3TC.
ART-naive ptsVL ≥ 1000 c/mL
HLA-B*5701 negCrCl > 50 mL/min
(N = 833)
DTG 50 mg QD + ABC/3TC QD(n = 414)
EFV/TDF/FTC QD (n = 419)
SPRING-2[30]
(active controlled, double blind)
SINGLE[31]
(active controlled, double blind)
DTG 50 mg QD + 2 NRTIs*(n = 242)
DRV/RTV 800/100 mg QD + 2 NRTIs*(n = 242)
ART-naive ptsVL ≥ 1000 c/mL
(N = 484)
FLAMINGO[32]
(open label)
30. Raffi F, et al. Lancet. 2013;381:735-743. 31. Walmsley S, et al. N Engl J Med. 2013;369:1807-1818.32. Feinberg J, et al. ICAAC 2013. Abstract H1464a. .
88 86
85
88 88
81
90 90
83
VL
< 5
0 at
Wk
48
VL
< 5
0:
DT
G/A
BC
/3T
C
• Samples from participants meeting Protocol defined Virological failure criteria were sent for resistance testing.
• No participants on DTG have had emergence of a virus with an INI resistance mutation.
• One participant receiving DTG 10mg developed virus with the mutation M184M/V in reverse transcriptase.
Resistance on SPRING 1
• No treatment-emergent genotypic resistance that resulted in reduced susceptibility to either DLG or the background regimen was seen in the DLG arm in SINGLE.
SINGLE
• Increase the dose of DLG- poor evidence• Category B drug.
OF course the ever present TB and pregnancy question
DLV/ABC and TDF
• In treatment-naive HIV-infected patients starting initial ART, dolutegravir (DTG) plus abacavir (ABV)/lamivudine (3TC) maintained superiority over efavirenz (EFV)/tenofovir DF (TDF)/emtricitabine (FTC) at Week 96 – DTG arm associated with higher virologic response rate, primarily
due to lower rate of discontinuations related to tolerability – DTG arm associated with more favorable safety profile vs control
arm, with lower rates of central nervous system (CNS) events, rash, and liver function test elevations
• No major treatment-emergent mutations conferring INSTI or NRTI resistance detected through 96 weeks in DTG-treated patients
Dolutegravir
FDC YESSingle day dosage YESLow side effect profile
YES High barrier to resistance
YEsTB friendly NOPregnancy friendly UNK
Darunavir dosing summary
Darunavir/r dosing is determined by treatment experience and presence or absence of darunavir mutations on genotypic lab analysis.
Treatment-experienced patients
• POWER 1 compared the efficacy and safety of four doses of DRV (TMC114) plus 100 mg RTV with investigator-selected control protease inhibitors (CPIs)
• 63% of the patients were resistant to all commercially available PI.
• Virologic and immunologic outcomes were significantly better in the DRV/r arms compared to the CPI arm. In the 600 mg DRV twice daily arm, mean CD4 gains were as high as 124 cells at 24 weeks and 53 percent attained an HIV RNA level <50 copies/mL;
Treatment-experienced patients
• POWER 3 DRV/r plus optimized background therapy. No comparator arm was used.
• Of 324 patients who were treated for 48 weeks, 45 percent achieved HIV RNA reductions to <50 copies/ml.
Treatment-experienced patients
• Treatment-experienced patients with recent genotypic testing demonstrating the absence of darunavir-associated mutations: darunavir (800 mg) once daily plus ritonavir (100 mg) once daily. The relevant darunavir mutations include: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V.
Treatment-experienced patients
• POWER 1 and POWER 2 were randomized, multinational, phase IIB trials, which compared DRV co-administered with low-dose RTV to other PIs in a population of highly treatment-experienced patients
Treatment-experienced patients
• Darunavir-associated mutations on genotype: darunavir (600 mg; given as one tablet) twice daily plus ritonavir (100 mg) twice daily.
• The relevant darunavir mutations include: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V.
Treatment-naïve patients
• Darunavir (800 mg) once daily plus ritonavir (100 mg) once daily
• ARTEMIS: randomized, open-label, phase 3 non-inferiority trial compared the safety and efficacy of DRV/r (800/100 mg once daily) with LPV/r in 689 treatment-naive patients
Treatment-naïve patients
• At week 48, DRV/r was found to be non-inferior to LPV/r; viral suppression was achieved in 84 versus 78 percent, respectively.
• At 96 weeks, significantly more patients in the DRV/r arm achieved viral suppression than in the LPV/r arm (79 versus 71 percent)
• Both treatments were well tolerated.
Darunavir
FDC NOSingle day dosage MAYBELow side effect profile
YES High barrier to resistance
YESTB friendly NOPregnancy friendly UNK
Third line Peer Revivew committee
• Third line drugs now on tender• Centrally procured
– Receive motivation– Screen– Add to database– Send to Virtual Committee – Committee recommendation to motivator and
CPU– Update database