When to Start HIV Treatment? Which Treatments to Start?

When to Start HIV Treatment? Which Treatments to Start? Calvin Cohen MD Harvard Medical School Harvard Vanguard Medical Associates CRI New England Vice Chair, Science Steering Cmte, INSIGHT Boston USA

When to start HIV treatment Late clinical stages Early clinical stages < 200 > 500 High viral load 200 350 Any viral load CD4 Adapted from Schechter M, JID 2004;190:1043-1045

Four Questions for Deciding When to Start Is there damage done by waiting to start treatment for patients with high T4 counts e.g., >500/mm 3? If yes, is the damage done by delaying HIV treatment completely reversible? At what CD4 count does the damage become irreversible? Are HIV treatments sufficiently ideal to treat everyone who is willing even those at very low risk of HIV-related illness?

Years lived Current Life Expectancy of HIV-Positive Patients Comparison of life expectancy of Athena cohort patients (n=4,174) to general population Years of Life Remaining Age at time of death Remaining Life Years General Population Asymptomatic HIV+ Patients Age at 24 weeks (years) van Sighem A, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 526.

CIPRAHT001: Randomized Trial of When to Start ART: Haiti Randomized clinical endpoint study of when to start therapy Treatment-naive No hx AIDS-defining illness CD4 200-350 (n=816) Early Treatment (Immediate ZDV/3TC + EFV) Standard Treatment (Delay until CD4+ <200 or AIDS Primary endpoint: Survival Baseline Characteristics Early (n=408) Standard (n=408) Median age (years) 40 40 Male (%) 41% 44% Median CD4+ (cells/mm 3 ) 280 282 May 2009: DSMB review stopped study due to excess deaths in Standard Treatment arm Severe P, et al. 49 th ICAAC; San Francisco, CA; Sept. 12-15, 2009; Abst. H-1230c.

CIPRAHT001: Clinical Endpoints Clinical Endpoints Early Rx Standard Hazard Ratio (p value) Death 6 23 4.0 (.0011 ) Incident Tuberculosis 18 36 2.0 (.0125 ) Infectious causes of death Early: 1 (gastroenteritis) Standard: 17 (7 gastroenteritis, 5 TB, 4 pneumonia, 1 cholangitis/sepsis) Severe P, et al. 49 th ICAAC; San Francisco, CA; Sept. 12-15, 2009; Abst. H-1230c.

EACS Guidelines: When to Start ARV Therapy In serodiscordant couples early initiation of ART as one aspect of the overall strategy to reduce HIV transmission to the seronegative partner should be considered and actively discussed Condition C = CONSIDER. D = DEFER. R = RECOMMENDED Current CD4 + lymphocyte count 350-500 >500 Asymptomatic HIV infection C D Symptomatic HIV disease (CDC B or C conditions) incl. tuberculosis R R Primary HIV infection C C Conditions (likely or possibly) associated with HIV, other than CDC stage B or C disease: HIV-associated kidney disease R R HIV-associated neurocognitive impairment R R Hodgkin's lymphoma R R HPV-associated cancers R R Other non-aids-defining cancers requiring chemo- and/or radiotherapy C C Autoimmune disease otherwise unexplained C C High risk for CVD (>20% estimated 10 yr risk) or history of CVD C C www.eacs.eu (October, 2011)

2011 DHHS Guidelines: Recommendations for Initiation of ART in Naïve Patients Clinical Category CD4 Cell Count (cells/mm 3 ) 2009 DHHS Guidelines Strength-Quality AIDS-defining illness Any value Treat <350 Treat A-I Asymptomatic 350 to 500 Treat A/B-II: 55% A vs. 45% B >500 Treat/Optional B/C-III: 50% B vs. 50% C Pregnancy, HIVassociated nephropathy, HIV/HBV when HBV treatment indicated Any value Treat A-III Note: HIV RNA >100,000 c/ml and decline of CD4+ count > 100 cells/mm 3 per year favor starting ART Strength of Recommendation: A = Strong; B = Moderate; C = Optional Quality of Evidence for Recommendation: I = data from randomized controlled trials; II = data from well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = expert opinion Available at: http://www.aidsinfo.nih.gov/contentfiles/adultandadolescentgl.pdf. Revision December 1, 2009.

IAS-USA 2010: Guidelines for When to Start ARV Therapy Measure Specific conditions Symptomatic HIV disease Pregnancy High HIV-1 RNA Level (>100,000 copies/ml) Rapid CD4 count decline (>100 cells/mm 3 per year) Active hepatitis B or C* virus co-infection Active or high risk for cardiovascular disease* HIV-associated nephropathy Symptomatic primary HIV infection* Age > 60* Recommendation ART recommended regardless of CD4 cell count Risk for secondary HIV transmission is high* CD4 cell count 500 cells/mm 3 ART recommended CD4 cell count >500 cells/mm 3 ART should be considered * Differs from 2009 DHHS guidelines Unless patient is an elite controller (HIV-1 RNA <50 copies/ml) or has stable CD4 cell count and low-level viremia in the absence of ART Thompson MA, et al. JAMA 2010;304(3):321-333; US Department of Health and Human Services Guidelines; Revised December 1, 2009. Available at: http://aidsinfo.nih.gov/contentfiles/adultandadolescentgl.pdf.

Results of Three Large Observational Cohorts At what CD4 count does evidence of clinical harm (incr. risk of AIDS and/or death) begin when deferring starting Antiretroviral Therapy? ART-CC: < 350/mm 3 Cascade: < 500/mm 3 NA-ACCORD: Any delay, including > 500/mm 3 Sterne J, at al. 16th CROI; 2009; Montreal. Abstract 72LB., Funk MJ, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. THLBB201., Kitahata M, et al. New Engl J Med 2009;360:1815-26

Cum. Probability (X100) SMART Naïve/Off Treatment Sub-study: Clinical Outcomes of (re-)starting ARVs 25 20 15 Opportunistic disease and death Hazard Ratio = 4.38 (95%.CI: 1.45-13.2) p=0.009 Deferred ART Immediate ART 25 20 15 Composite endpoint Hazard Ratio = 5.08 (95% CI: 1.91-13.5) p=0.001 10 10 5 5 No. at Risk Deferred ART 228 Immediate ART 249 0 0 4 8 12 16 20 24 28 32 36 192 210 Continuous ART Intermittent ART 162 179 130 144 Months 95 124 73 104 58 80 37 58 26 44 21 35 0 0 4 8 12 16 20 24 28 32 36 No. at Risk Months 228 249 188 210 157 179 125 144 90 124 Last CD4+ cell count (cells/ml) < 250 250-349 350-499 > 500 Overall Event Rate * 10.4 6.7 1.8 0.0 1.3 Event Rate * 16.0 9.2 7.6 3.1 7.0 69 104 55 79 33 57 24 43 20 35 per 100 person years Emery S, et al. JID 2008; 197: 1133 1144.

SMART: Non-AIDS event rates with Continuous vs. Intermittent ART Endpoint Continuous (n=2752) Intermittent (n=2720) HR (95% CI) P Value Any cause death 30 55 1.8 (1.2-2.9).007 Major CV, renal, or hepatic disease Fatal/nonfatal CV disease Fatal/nonfatal renal disease Fatal/nonfatal liver disease 39 65 1.7 (1.1-2.5).009 1.1% 1.8% 1.6 (1.0-2.5).05 0.07% 0.3% 4.5 (1.0-20.9).05 0.25% 0.4% 1.4 (0.6-3.8).46 Adapted from El-Sadr WM, et al. N Engl J Med 2006;355:2283-96.

Immunodeficiency and Risk of Non-AIDS Defining Cancers Adjusted HR vs. non HIV* HIV Infected, CD4+ Cell Count, cells/mm 3 < 200 201-499 500 P Value Any infection related 12.8 5.9 3.2 <.001 Anal 164.2 83.1 34.2 <.001 Hodgkin s lymphoma 55.0 11.0 11.6 <.001 Oral/pharyngeal 3.1 1.9 0.8.030 Infection unrelated 1.8 1.2 1.1.002 Melanoma 1.3 1.9 1.9.71 Lung 2.1 1.0 1.2.083 Colorectal 2.2 1.0 0.9.050 HIV-1 RNA levels not significantly associated with non-aids defining cancers * Adjusted for age, sex, smoking, overweight, alcohol/drug abuse, viral hepatitis; reference = uninfected cohort. P <.001 relative to uninfected. P <.05 relative to uninfected. Silverberg M, et al. CROI 2010. Abstract 28 and AIDS 2009.

Percent Difference Inflammatory markers are increased in ART-treated HIV+ patients vs. HIV- 200 175 Participants aged 45-76 years 150 125 100 75 50 25 0 hs-crp IL-6 D-dimer Cystatin-C Unadjusted Adjusted for age, gender, race Fully adjusted Adapted from Neuhaus J, et al. J Infect Dis. 2010;201(12):1788-95. 14

Cumulative Probability of Event SMART: Hyaluronic Acid Levels in Hepatitis Coinfected Subjects Predict Non-AIDS Death Evaluation of impact of treatment interruption on liver fibrosis in SMART subjects with hepatitis coinfection (n=675) Baseline HA levels (>75 ng/ml) strong predictor of non- AIDS death in DC group Risk of Non-AIDS Death in HIV+, Hepatitis Coinfected According to Baseline HA and Treatment ARM 50 45 40 35 30 25 20 15 DC Group, HA >75 DC Group, HA 75 VS Group, HA >75 VS Group, HA 75 10 5 0 0 4 8 12 16 20 24 28 32 36 40 44 48 Months from Randomization DC =Drug Conservation; VS=Virologic Suppression Log rank test: P <.0001 (overall) P <.0001 (DC + HA >75 vs 3 other groups) P =0.35 (3 groups other than DC + HA >75) 15 Peters L et al.16th CROI; 2009; Montreal. Abstract 858.

HPTN 052: Treatment as Prevention Randomized, placebo-controlled efficacy and safety study 13 sites in Africa, Asia, Americas: N=1763 HIV-positive patients in relationship with HIVnegative partner 97% Heterosexual CD4 350-550 N= 886 immediate HAART N=877 Delayed HAART until CD4<250 (or AIDS) N=1 transmission 96% risk reduction N=27 transmissions All received ongoing safe sex education/condoms Study stopped four years early by DSMB (May 2011) All 28 transmissions genetically linked to the positive partner All on delayed arm now offered HAART Available at: http://www.hptn.org/web%20documents/pressreleases/hptn052pressreleasefinal5_12_118am.pdf Accessed May 12, 2011.

HPTN 052: Clinical Endpoints N=105 had primary clinical endpoint* Immediate: 40 Delayed: 65 HR: 0.6 (0.4,0.9) P=0.01 Extrapulmonary TB: largest difference favoring early treatment (P<0.002) Adverse events: Immediate: 24% Delayed: 5% Immediate Total (N=129) 53 76 Tuberculosis 17 33 Severe bacterial infection 16 11 Death 10 13 Chronic herpes simplex Bacterial pneumonia (recurrent) Esophageal candidiasis 3 7 2 2 2 2 Delayed Grinstein B, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. MOAX0105, 2011. *Some pts had >1 event

www.clinicaltrials.gov START Study: Design HIV-infected individuals who are ART-naïve with CD4+ count > 500 cells/mm 3 Early ART group Initiate ART immediately following randomization N=2,000 Deferred ART group Defer ART until the CD4+ count declines to < 350 cells/mm 3 or AIDS develops N=2,000 Rate of primary endpoint in deferred group: 2.8 per 100 PY Non-AIDS : AIDS events = 4:1 Early ART reduces rate of primary endpoint by 28.8% 43% for AIDS and 24% for non-aids

What to Start?

Which Antiretrovirals: 2012 Currently Available in the US NRTIs Abacavir Didanosine NNRTIs Delavirdine Efavirenz PIs Atazanavir Darunavir Fusion inhibitors Enfuvirtide Emtricitabine Etravirine Fos-Amprenavir Lamivudine Nevirapine Indinavir Stavudine Nevirapine XR Lopinavir Entry inhibitors Tenofovir Rilpivirine Nelfinavir Maraviroc Zidovudine Ritonavir Saquinavir Tipranavir Integrase inhibitors Raltegravir

EACS Guidelines: Ten Initial Combination Regimens 1 drug in column A 1 NRTI combination A B REMARKS Recommended EFV NVP NNRTI Ritonavirboosted PI ATV/r DRV/r LPV/r Integrase Inhibitor RAL C = CONSIDER. D = DEFER. R = RECOMMENDED www.eacs.eu. (October 2011) ABC/3TC or TDF/FTC TDF/FTC ABC/3TC or TDF/FTC TDF/FTC TDF/FTC co-formulated ABC/3TC co-formulated EFV/TDF/FTC co-formulated ATV/r: 300/100 mg qd DRV/r: 800/100 mg qd LPV/r: 400/100 mg bid or 800/200 mg qd RAL: 400 mg bid

EACS Guidelines: Initial Combination Regimen 1 drug in column A 1 NRTI combination A B REMARKS Alternative SQV/r FPV/r MVC ZDV/3TC ddl/3tc or FTC SQV/r: start with 500/100 mg then change to 1000/100 mg bid after one week FPV/r: 700/100 mg bid or 1400/200 mg qd ZDV/3TC co-formulated C = CONSIDER. D = DEFER. R = RECOMMENDED www.eacs.eu. (October 2011)

2011 DHHS Guidelines: What to Start: Preferred Preferred Regimens: Regimens with optimal and durable efficacy, favorable tolerability and toxicity profile, and ease of use NNRTI: EFV/TDF/FTC EFV caution for women given risk of birth defects when EFV used in first trimester PI: ATV/r + TDF/FTC DRV/r (once daily) + TDF/FTC Int: RAL + TDF/FTC ATV/r should not be used in patient who require >20mg omeprazole equivalent per day RAL dosing BID Preferred Regimen for Pregnant Women LPV/r (twice daily) +ZDV/3TC Once-daily LPV/r is not recommended in pregnant women Comments: TDF should be used with caution in patients with renal insufficiency US Department of Health and Human Services Guidelines; Revised October 14, 2011 Available at: http://aidsinfo.nih.gov/contentfiles/adultandadolescentgl.pdf

2011 DHHS Guidelines: What to Start: Alternative Alternative Regimens - that are effective and tolerable but have potential disadvantages compared with preferred regimens. An alternative regimen may be the preferred regimen for some patients. NNRTI Based Regimens: EFV + ABC/3TC (BI) RPV/TDF/FTC (BI) RPV + ABC/3TC (BIII) Use RPV with caution in patients with pretreatment HIV RNA >100,000 copies/ml Use of proton pump inhibitors is contraindicated with RPV PI Based Regimens (alphabetically) ATV/r + ABC/3TC (BI) DRV/r + ABC/3TC (BIII) FPV/r (QD or BID) + ABC/3TC or TDF/FTC (BI) LPV/r (QD or BID) + ABC/3TC or TDF/FTC (BI) INSTI Based Regimen RAL + ABC/3TC (BIII) RAL dosed twice daily Comments for abacavir: Should not be used in patients who test positive for HLA-B5701 Use with caution in patients with known high risk of cardiovascular disease or with pretreatment HIV RNA >100,000 copies/ml US Department of Health and Human Services Guidelines; Revised October 14, 2011 Available at: http://aidsinfo.nih.gov/contentfiles/adultandadolescentgl.pdf

Probability of remaining free of virologic failure A5202: Two NRTIs plus EFV or ATV/r: Impact of baseline viral load and CD4 count ABC/3TC TDF/FTC 1 HIV RNA 100,000 c/ml HIV RNA < 100,000 c/ml 0.8 0.6 0.4 n=98 35 VF n=78 23 VF n=80 19 VF n=153 10 VF n=39 6 VF n=273 28 VF n=23 5 VF n=184 29 VF 0.2 n=80 6 VF n=83 17 VF n=70 9 VF n=158 19 VF n=55 8 VF n=289 29 VF n=20 2 VF n=173 24 VF 0 CD4 (cells/mm 3 ) <50 50 to <200 200 to <350 350 Adapted from Grant P, et al. 18th CROI; Boston, MA; February 27-March 2, 2011. Abst. 535. 25

Relative risk (95% CI) D:A:D Study: NRTIs and risk of MI Recent Exposure*: yes/no 1.9 1.5 1.2 1 0.8 0.6 ZDV ddi d4t 3TC ABC TDF #PYFU: 138,109 74,407 95,320 152,009 53,300 39,157 #MI: 523 331 405 554 221 139 * Recent use=current or within the last 6 months. Adapted from Lundgren JD, et al. 16th CROI; Montreal, Canada; February 8-11, 2009. Abst. 42LB.

RR/year (95% CI) D:A:D Study: PIs/NNRTIs and Risk of MI Risk with Cumulative Exposure Effect of Adjustment for Latest Metabolic Factors 1.2 PI* NNRTI Lopinavir/r Indinavir 1.13 Primary model Dyslipidemia 1 Elevated blood pressure Diabetes mellitus Lipodystrophy 0.9 Glucose IDV NFV LPV/r SAQ NVP EFV #PYFU: 68,469 56,529 37,136 44,657 61,855 58,946 #MI: 298 197 150 221 228 221 All above + lipid-lowering and 0.9 1 1.1 1.3 1.4 antihypertensive RR of MI (95% CI) medication * Approximate test for heterogeneity: P=0.02 Lundgren JD, et al. 16th CROI; Montreal, Canada; February 8-11, 2009. Abst. 42LB.

The third drug : A review EFV never surpassed ATV/r, RAL: Noninferiority shown NVP: Fewer severe AEs, no CD4 restrictions PIs: ATV/r and DRV/r show advantages over LPV/r ATV/r: Less diarrhea (Castle) DRV/r: More forgiveness (Artemis) RAL Twice daily dosing

Absence of Primary Protease Mutations in First-Line Therapy With PI/r Study n NRTI backbone PI/r Week Genotypes Primary PI mutations 720 1 100 d4t + 3TC LPV 312 17 0 863 2 653 d4t + 3TC LPV 108 51 0 940 3 44 d4t + 3TC LPV 72 13 0 056 4 38 d4t + 3TC LPV 72 5 0 418 5 190 TDF + 3TC LPV 96 15 0 Solo 6 649 ABC + 3TC FPV 64 32 0 Staccato 7 258 ddi + d4t SQV 19 48 10 0 BMS 089 8 95 d4t-xr + 3TC ATV 48 2 0 ARTEMIS 9 689 TDF + FTC LPV or DRV 96 NA 0 CASTLE 10 881 TDF + FTC LPV or ATV 96 52 1* *in ATV/r arm 1. Gulick R, et al. 7th ICDTHI, 2004; Abstract P28. 2. Kempf D, et al. J Inf Dis 2004;189:51; 3. Cahn P, et al. 1st IAS, 2001; Abstract 779. 4. Feinberg J, et al. 14th IAC, 2002; Abstract TuPeB4445. 5. Molina JM, et al. 15th IAC, 2004; Abstract WePeB570. 6. MacManus S, et al. AIDS 2004;18:65; 7. Ananworanich J, et al. 3rd IAS, 2005; Abstract WePe4.4C12; 8. Malan N, et al. CROI 2006; Abstract 107LB. 9. Mills T, et al. 48th ICAAC/46th IDSA, 2008; Abstract H-1250c. 10. Molina J-M, et al. 48th ICAAC/46th IDSA, 2008; Abstract H-1250d.

Pooled ECHO/THRIVE: Week 48 Incidence of Treatment-emergent a RT mutationsby Baseline Viral Load Category 30 Incidence, n (%) RPV (N = 686) EFV (N = 682) All virologic failure with genotypic data b n = 62 n = 28 NNRTI RAM 39 (63) 15 (54) N(t)RTI RAM 42 (68) 9 (32) NNRTI and N(t)RTI RAM 37 (60) 8 (29) Baseline viral load 100K c/ml (RPV n=368), (EFV, n=330) n = 16 n =12 NNRTI RAM 61.6% (38) 51.5% (42) N(t)RTI RAM 7 (44) 2 (17) N(t)RTI RAM 1.9% 0.6% NNRTI and N(t)RTI RAM 5 (31) 1 (8) NNRTI and N(t)RTI RAM 1.4% 0.3% Baseline viral load >100K c/ml (RPV, n=318), (EFV, n=352) n = 46 n = 16 NNRTI RAM 33 10.4% (72) 10 2.8% (63) N(t)RTI RAM 3511% (76) 72% (44) NNRTI and N(t)RTI RAM 3210% (70) 72% (44) a Not present at screening or baseline and present at time of failure while on treatment. b At time of failure. Rimsky L, et al. IWHHC 2011; Los Cabos, Mexico. Abstract 9.

Cohen C, et al. 5th IAS; Cape Town, South Africa; July 19-22, 2009; Abst. MOPEB063. FOTO: 48 Week Results Five-days On, Two-days Off N=60 On TDF / FTC / EFV HIV RNA<50 X 6 months All drugs fully active Change to FOTO* N=30 TDF/FTC/EFV QD N=30 Continue FOTO* N=23 Rollover to FOTO* N=27 24 wk Extension/rollover 48 wk *FOTO=TDF/FTC/EFV five days on followed by 2 days off treatment per week

Patient Percent Cohen C, et al. 5th IAS; Cape Town, South Africa; July 19-22, 2009; Abst. MOPEB063. FOTO: Virologic Outcomes Percent < 50 copies/ml at each time point 97% 93% 100%* 86% 90% 90% No virologic failure all blips followed by subsequent suppression *Primary outcome Wk 24; p<0.001 to reject inferiority of FOTO vs. Daily strategy for maintaining suppression

VAT change from week 0 (%) A5224s: Change in Visceral Adipose Tissue CT Results: Mean percent change in VAT (ITT) NRTI Component Secondary Analysis NNRTI/PI Component Secondary Analysis P = 0.55 P = 0.018 ATV/r average gain 1.8 kg trunk fat; EFV average gain 0.7 kg trunk fat. McComsey, G, et al. 18th CROI; Boston, MA; February 27-March 2, 2011. Abst. 77.

A5224s: Mean % Change in Lumbar Spine BMD P=0.004 P=0.035 * linear regression No significant interaction of NRTI and NNRTI/PI components (P=0.63) McComsey G, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 106LB.

Change in Calculated Creatinine Clearance, (ml/min) ACTG 5202: Median Change in Creatinine Clearance (Week 96, AT) 3TC/ABC FTC/TDF P =.33 7.8 P <.001 6.1 4.9-2.6 ATV/r EFV ATV/r EFV n= 330 287 352 327 P values: ATV/r vs EFV Daar E et al. CROI 2010. Abstract 59LB.

Percentage of Patients Adherence: On time Pharmacy Refills by Number of Tablets per Day Single Tablet Regimen Multi-Tablet Regimen p<0.01 11% have better adherence to STR p<0.01 p<0.01 p<0.01 N = 122 690 427 1686 824 2454 465 1044 <60% >60-79% 80-94% 95-100% Adherence to Antiretroviral Therapy Cohen CJ et al. ESPACOMP Nov 2011, Utrecht. Oral 315

Pooled ECHO/THRIVE: Adverse Event Summary at Week 96 RPV N=686 EFV N=682 Median treatment duration, weeks 104 104 Incidence, n (%) All All p-value Discontinuations due to AEs 28 (4) 58 (9) 0.0008 Most common AEs of interest Any neurological AE 119 (17) 259 (38) <0.0001 Dizziness 55 (8) 182 (27) <0.0001 Any psychiatric AE 107 (16) 166 (24) <0.0001 Abnormal dreams/nightmares 57 (8) 90 (13) 0.0039 Rash (any) 29 (4) 103 (15) <0.0001 Cohen C, et al. IAS 2011, TULBPE032

Pooled ECHO and THRIVE: Week 48 Outcome by Adherence and Viral Load Adherent (>95%) Suboptimally Adherent BL VL <100K BL VL >100K BL VL <100K BL VL >100K RPV EFV RPV EFV RPV EFV RPV EFV Virologic Responder 95% 92% 87% 92% 47% 39% 31% 37% Virologic Failure 3% 4% 10% 4% 21% 11% 50% 17% Other D/C 2% 5% 2% 4% 31% 50% 19% 46% Rimsky L, et al. ICAAC 2010, H-1810.

Percent < 50 c/ml at Week 48 EVG/c/TDF/FTC vs. Two Preferred Regimens Virologic Responses (< 50c/mL) at Week 48 84% 88% 87% 90% 95% CI: (-1.6%, +8.8%) 95% CI: (-1.9, + 7.8%) Gilead press release, 8/15/2011 and 9/19/2011, accessed on www.gilead.com

The Future: More ARVs, More Fixed Single Tablet Regimens NNRTIs EFV/FTC/TDF RPV/FTC/TDF Integrase inhibitors EVG/cobi/FTC/TDF DOL/ABC/3TC Protease inhibitor DRV/cobi/FTC/pro-TDF ATV/cobi

Stalemate? Or a Cure? may HIV flow from our blood into our history books. - William Jefferson Clinton 10 th Retrovirus Conf. Boston 2003