ART: The New, The Old and The Ugly. Our Current ARVS The Nucleoside/ Nucleotide Reverse Transcriptase Inhibitors (NRTIs/ NtRTIs) The Non-Nucleoside Reverse

ART: The New, The Old and The Ugly

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/



Inhibitors (NNRTIs)


(PIs)

AbacavirDidanosine

EmtricitabineLamivudineStavudineTenofovir

Zidovudine

EfavirenzNevirapineEtravirineRilpivirine Amprenavir

AtazanavirDarunavirIndinavirLopinavirRitonavir

Saquinavir

The Integrase Inhibitors (ISTIs)

Raltegravir Fixed-drug combinations


Triomune, Atripla, Tripalvar, Complera

THE ANTIRETROVIRAL DRUGS

The Nucleoside/



Inhibitors (NNRTIs)


(PIs)

AbacavirDidanosine

EmtricitabineLamivudineStavudineTenofovir

Zidovudine

EfavirenzNevirapineEtravirineRilpivirine

AmprenavirAtazanavirDarunavirIndinavirLopinavirRitonavir

Saquinavir Tipranavir

The Integrase Inhibitors (ISTIs)

Raltegravir ElvitegravirDolutegravir

Fixed-drug combinations


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

Etravirine

FDC NOSingle day dosage NOLow side effect profile

YES High barrier to resistance

?TB friendly NOPregnancy friendly UNK

Rilpivirine

Rilpivirine

• Novel NNRTI• Single day dosage • Co-formulated with TDF and FTC as Complera

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


NOTB friendly NOPregnancy friendly UNK

Raltegravir

• Novel mode of action• Acts on intergrase as an inhibitor • 400mg bd

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)


(n = 51)

Efavirenz +Tenofovir + Lamivudine

(n = 52)

Wk 24Primary endpoint Wk 48


*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


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



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.


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)


(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



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;


• 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 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.


• 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


• 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


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

Third line committee

• 130 patients on the database.• 115 have already been reviewed.• (5 motivations no GT results)• Number of motivations declined 12 • Number of patients on third line treatment 98

Documents

ART: The New, The Old and The Ugly. Our Current ARVS The Nucleoside/ Nucleotide Reverse Transcriptase Inhibitors (NRTIs/ NtRTIs) The Non-Nucleoside Reverse