4 Rekomendacje europejskie (EACS) Rekomendacje amerykańskie (DHHS) Rekomendacje polskie Kiedy zacząć ?
5 HAART and Survival Based on Initial CD4+ Cell Count Modeled data from ART Cohort Collaborative10,855 patients included934 progressed to AIDS or diedIDUs excluded from modelCumulative Probability of AIDS/Death According to CD4+ Cell Count at Initiation of HAARTcells/mm cells/mm cells/mm3123450.000.020.040.060.080.100.12Probability of AIDS or DeathProgression and Death According to CD4+ Cell Count (cells/mm3)< 200 vs< 350 vsHazard ratio for AIDS (95% CI)( )1.52( )Hazard ratio for AIDS or death (95% CI)( )1.26( )For more information, go to the Capsule Summary atYears Since Initiation of HAARTSterne J, et al. CROI Abstract 525.
6 CD4+ Cell Count Response Based on Baseline CD4+ Cell Count Johns HopkinsHIV Clinical Cohort10008006004002004896144192240288336ATHENA National CohortWeeks From Starting HAART2004006008001000Mean CD4+ Cell Count (cells/mm3)For more information, please see the Capsule Summary at12345Years on HAARTMagnitude of CD4+ cell count increase greatest if therapy started at low CD4+ cell counts, but greater likelihood of CD4+ cell count normalization with earlier therapyKeruly J, et al. CROI Abstract 529. Gras L, et al. CROI Abstract 530.
7 Związek pomiędzy śmiertelnością a supresją wiremii Prospektywne, Danish HIV Cohort StudyN = 3919 HIV(+)HAART ≥ 18 miesięcyPodzieleni na grupy w zależności od proporcji wykrywalnej wiremii w ciągu 18 miesięcy od włączenia leczeniaWiększe ryzyko śmierci u osób z niepełną lub brakiem supresjiProportion of Detectable Viral Loads Over 6-18 Months After Initiation of HAART100% (all values VL ≥ 400)1%-99% (of values VL ≥ 400)0% (all values VL < 400)0.250.200.150.100.050.0018365472HAART, highly active antiretroviral therapy; VL, viral load.For more information, please go online to:Cumulative MortalityMonths After Baseline (baseline = 18 months after HAART initiation)Lohse N, et al. ICAAC Abstract H-515.
8 Kiedy rozpoczynać HAART : HOPS Cohort Dane z kohorty >8000pts, obserwacja od 1993U pacjentów, którzy zaczynali HAART przy wyższym CD4+Mniejsza śmiertelność, mniej OILepsza odpowiedź CD4+ na HAARTRzadziej niewydolność nerek, neuropatia i lipoatrofiaLepszy efekt immunologiczny u osób stale leczonych HAART vs STIKorzyści z leczenia nawet u osób, którzy rozpoczynali leczenie z CD kom/mm³ i > 500 kom/mm³ARVs associated with increased incidence of lipoatrophy in Year 1: IDV, NVP (P < .05); ≥ 2 years: d4T 30 mg BID (P < .05).ARVs associated with increased incidence of neuropathy in Year 1: d4T 30 mg BID, ddI, IDV, RTV ≥ 800 mg/day, NFV, SQV, APV (P < .05)Lichtenstein KA, et al. CROI Abstract 769.
9 Rekomendacje europejskie (EACS) Rekomendacje amerykańskie (DHHS) Rekomendacje polskie Czym zacząć ?
10 Boosted vs Unboosted Atazanavir in Antiretroviral-Naive Patients Randomization 1:1ATV 400 mg QD (n = 105)ATV/r 300/100 mg (n = 95)Both with d4T-XR 100 mg QD + 3TC 300 mg QDTrend for more virologic failure in ATV arm*Patients with VFATV: n = 10ATV/r: n = 3Mean CD4+ count changeATV: +224ATV/r: +189Weeks< 400 c/mL< 50 c/mL20406080100BL248121624324886%75%85%70%Responders (%)HIV RNA < 400 c/mL and < 50 c/mL Through Week 48 (ITT)For more information, please see the Capsule Summary atNot powered to determine if ATV noninferior to ATV/rDifference estimate (95% CI): 1.5 (-8.2 to 11.1) Difference estimate (95% CI): 1.5 (-7.0 to 17.0)ATV 300/RTV (n = 95) ATV 400 (n = 105)*Not powered to determine if ATV noninferior to ATV/rMalan N, et al. CROI Abstract 107LB.
11 ACTG 5095: Założenia badania Porównanie 2- vs 3 lekowego NRTI backbones i zestawu 3-NRTI vs zawierające EFVRamię 3-NRTI przerwano po analizie danych pokazujących mniejsza efektywność w stosunku do ramion zawierających EFVMedian follow-up: 144 weeks3-NRTI armZidovudine/lamivudine/abacavirEFV, efavirenz; VL, viral load.For more information, please go online to:Antiretroviral-NaiveVL ≥ 400 copies/mL(N = 82)3 NRTIs + EFV armZidovudine/lamivudine/abacavir + efavirenz2 NRTIs + EFV armZidovudine/lamivudine + efavirenzGulick RM, et al. ICAAC Abstract H-416a.
12 ACTG 5095: EFV + ZDV/3TC vs EFV + ZDV/3TC/ABC jako terapia inicjująca Ni stwierdzono różnicy w:Czasie osiągnięcia supresjiLiczbie niepowodzeń terapeutycznychProporcji z VL < 200 or < 50 c/mLOdpowiedzi CD4+Profilu opornościPodobne rezultaty u osób z VL > 100,000Czynniki niepowodzenia wirusologicznegoHCV (HR: 1.57)Black race (HR: 1.67)Płeć, wiek, CD4+ nie ma wpływu1008060Virologic Failures* (%)402526203TC, lamivudine; ABC, abacavir; BL, baseline; EFV, efavirenz; HCV, hepatitis virus C; HR, hazard ratio; VL, viral load; ZDV, zidovudine.For more information, please go online to:ZDV/3TC/ABC + EFV(n = 383)ZDV/3TC + EFV(n = 382)* Virologic failure defined as 2 consecutive VL ≥ 200 copies/mL at ≥ Week 16.Gulick RM, et al. ICAAC Abstract H-416a.
13 NRTI-Sparing Initial Therapy: LPV/r + SQV Compared With LPV/r + NRTIs Otwarte, randomizowane, pilotażowe badanieN = 30 naive menLPV/r (400/100 BID) + SQV (800 BID) or ZDV/3TC (300/150 BID)Podobne wyniki w 48 tygodniuNie różnią się objawami ubocznymiMniejsza liczba tabletek nowych postaci LPV/r and SQVPotrzeba więcej badań nad efektywnością dual-PI10078%8077%60Patients With HIV-1 RNA < 50 copies/mL (Observed Data) (%)403TC, lamivudine; BID, twice daily; LPV/r, lopinavir/ritonavir; PI, protease inhibitor; SQV, saquinavir; ZDV, zidovudine.In this trial, saquinavir was administered at 200 mg in the hard-gel capsule formulation.For more information, please go online to:20LPV/r + SQV LPV/r + ZDV/3TC12243648Weekn =1313n =109Cameron DW, et al. ICAAC Abstract H-523.
14 Odpowiedź na NNRTIs vs PIs u pacjentów z zaawansowanym AIDS Poprzednie badania sugerowały różnice w efektywności pomiędzy NNRTIs a PIs u pacjentów z zaawansowaną chorobąJednak oparte na badaniach obserwacyjnych i porównaniu różnych badańRandomizowane badanie porównujące EFV vs IDV/r u nieleczonych z CD4+ < 100 kom/mm3Nie ma statystycznych różnic w odpowiedzi wirusologicznejNie ma statystycznych różnic w odpowiedzi CD4+ w 24 miesiącuEFV, efavirenz; IDV/r, ritonavir-boosted indinavir.One of the most important choices made by HIV-treating clinicians is the initial antiretroviral regimen; this is particularly true in patients with very advanced HIV disease. Observational and cross-study comparisons have suggested that there may be a difference between using an NNRTI and a PI in patients with advanced disease. Furthermore, it has been suggested that patients with very advanced disease may have better responses with PIs.Investigators from Spain conducted a randomized controlled trial comparing the use of efavirenz with ritonavir-boosted indinavir in treatment-naive patients with advanced HIV disease, which was defined as a CD4+ cell count < 100 cells/mm3. Overall, there was no significant difference in virologic response to PIs or NNRTIs, and after 2 years, there was no significant difference in CD4+ cell counts between groups. This suggests that the choice of effective antiretroviral therapy in patients with advanced HIV disease is reasonably broad and should not be limited to one class of antiretroviral drugs.For more information, please go online to:Miro JM, et al. EACS Abstract PS1/4.
15 DART: Use of TDF + ZDV + 3TC in Resource-Limited Settings Potential advantages of regimenNo refrigerationNo hypersensitivityNo pregnancy concernsNo rifampin interactionsRandomized trial: clinical + lab vs clinical monitoring alone in naive pts starting ZDV/3TC + TDF48-wk results presented on 300 pts in virology substudyBL median CD4+, 100 cells/mm3BL median VL, 279,910 copies/mL2040608010055%65%62%74%% of Subjects< 50 at Wk 48< 400 at Wk 48ITT M=FOT3003.722314.20Mean log drop:n =Kaleebu P, et al. IAS Abstract WeOaLB0203.
16 Rekomendacje europejskie (EACS) Rekomendacje amerykańskie (DHHS) Rekomendacje polskie Jak zmieniać? ?
17 Zmiana na prostszy schemat SWAN study: efektywność i bezpieczeństwo zmiany z reżimu PI BID i/lub ≥ 3 tabl/dizennie na ATV (n = 253) lub ATV/r, jeśli z TDF (n = 25)Kryteria wejścia: na stabilnym HAART z PI-, na 1st lub 2nd zestawie, VL < 50 przez ≥ 3 monthsRandomizowano na dwie grupy-zmiana lub pozostanie na dotychczasowym leczeniuPatiencji, którzy otrzymali ATV:Utrzymali supresję wirusologicznąMieli poprawę profilu liidówTotal cholesterol, -16% vs +1% with comparator PI (P < .0001)Triglycerides, -38% vs +1% with comparator PI (P < .0001)Gatell JM, et al. IAS Abstract WePe6.3C15.
18 Leczenie podtrzymujące monoterapią PI Monoterapia podtrzymująca stanowi atrakcyjną opcję dla u pacjentów z supresją wiremiiJednakże w poprzednich badaniach stwierdzono znaczne ryzyko niepowodzenia wirusologicznegoPI/r mogą być dobrą opcją: ↑ potencjał, ↓ ryzyko oporności20/24 miało wiremię nieoznaczalną 48 tygodniu po zmianie LPV/r + 2 NRTIs to LPV/r monoterapię Niepowodzenie wirusologiczne nie powodowało rozwoju mutacji , a dodaniem NRTIs uzyskano supresjęIn virtually all monotherapy studies, there have been unexplained failures (no resistance, good adherence, adequate drug levels), which is one reason why compartment issues are being raised.1. Arribas JR, et al. IAS Abstract WePe12.3C05.2. Vernazza P, et al. IAS Abstract WeOa0204.
19 Pharmakokinetyka of Double-Boosted zestawów z ATV Pharmacokinetics of double-boosted PI therapy assessed in observational Frankfurt HIV cohortCompared to each single-boosted PI + NRTIsATV also reduces RTV levels when combined with LPV/rSecondary boosting effect of ATV on LPVAUCss After 3 Days of Treatment (ng·hr/mL)Effect on Concomitant DrugEffect on ATVRecommendationLopinavir/ritonavir (400/100 BID)↓ 16% (P = .21)↓ 22% (P = .077)Use with TDMSaquinavir/ritonavir (1000 BID/100 QD)↑ 40% (P = .001)↑ 16% (P = .11)Use with low-dose ritonavir (100 mg QD)Fosamprenavir/ritonavir (700/100 BID)neutral↓ 31% (P = .003)Further investigation requiredATV, atazanavir; AUCss, area under the curve at steady state; BID, twice daily; LPV, lopinavir; LPV/r, ritonavir-boosted lopinavir; QD, once daily; RTV, ritonavir; TDM, therapeutic drug monitoring.The use of double-boosted PI regimens is practiced widely without substantial clinical evidence to suggest its effectiveness. Nevertheless, one of the challenges of using such regimens is the complicated drug interactions that occur between PIs. An analysis of patients in the Frankfurt HIV cohort examined the pharmacokinetic effects of using atazanavir in double-boosted PI regimens.In patients given atazanavir with ritonavir-boosted lopinavir, a modest 16% decrease in the area under the curve at steady state for lopinavir and a modest 22% reduction in the area under the curve at steady state for atazanavir was observed. The recommendation from the investigators was that therapeutic drug monitoring would be useful when using a double-boosted PI regimen consisting of atazanavir and ritonavir-boosted lopinavir.When atazanavir was used with ritonavir-boosted saquinavir, atazanavir increased the area under the curve at steady state of saquinavir quite significantly, by 40%, whereas saquinavir did not have a significant effect on atazanavir. The investigators recommended that if this combination is used, a lower dose of ritonavir may be appropriate.Finally, the use of atazanavir in combination with ritonavir-boosted fosamprenavir had no effect on fosamprenavir; however, ritonavir-boosted fosamprenavir reduced the area under the curve at steady state of atazanavir by 31%, suggesting that additional investigation is required. These data only serve to demonstrate the complexity of drug interactions in double-boosted PI regimens. Additional investigation is required, in general, regarding the concept of double-boosted PI use.For more information, please go online to:P values for PI/r + ATV vs PI/r alone.1. von Hentig N, et al. EACS Abstract PS6/5.2. von Hentig N, et al. EACS Abstract PS6/6.
20 COMET: Switch From ZDV/3TC to TDF/FTC 189 suppressed patients switched from ZDV/3TC to TDF/FTCPrimary reason for switch: simplification (86%)All had BL VL < 400 copies/mLSmall, but significant improvement in lipidsTC ↓ 13 mg/dL at Week 12TG ↓ 12.5 mg/dL at Week 12Hb increased 0.6 g/dL by Week 24By Week 24 after switch26 (14%) had increases in VL114 (60%) maintained VL49 (26%) had decreases in VLWeek 24 copies/mL (n)BL VL copies/mL> 40050–400< 5050–400 (n = 78)< 50 (n = 111)3TC, lamivudine; BL, baseline; FTC, emtricitabine; Hb, hemoglobin; TC, total cholesterol; TDF, tenofovir disoproxil fumarate; TG, triglycerides; VL, viral load; ZDV, zidovudine.Note to viewer: please view slide in slideshow modeThere are several caveats that must be considered when interpreting these results. Caveats include that this was an uncontrolled nonrandomized study, that patients probably had reasons for wanting to switch, and that viral loads were not done centrally and may have been subject to false positives which are common with improper viral load specimen handling.For more information on this study, please go online to:9314209449Ruane P, et al. EACS Abstract PE7.3/5.
21 Rekomendacje europejskie (EACS) Rekomendacje amerykańskie (DHHS) Rekomendacje polskie Jak nie zmieniać?
22 COL40263: Once-Daily ZDV/3TC/ABC + Tenofovir Genotypes of Nonresponders*100All patients BL VL < 100,000 BL VL ≥ 100,000K65R/K (2 of 14 isolates)80≥ 1 TAMs only (3 of 14 isolates)M184V only (1 of 14 isolates)60≥ 1 TAMs + M184V (4 of 14 isolates)Wild type (4 of 14 isolates)< 50 copies/mL (ITT: M=F) (%)Patients With HIV-1 RNA4014%21%7%29%3TC, lamivudine; ABC, abacavir; BL, baseline; ITT: M=F, intent to treat: missing equals failure; TAMs, thymidine analogue mutations; VL, viral load; ZDV, zidovudine.COL40263 is an open-label study of a novel once-daily regimen: coformulated abacavir/lamivudine/zidovudine plus tenofovir DFIn an ITT (missing = failure) analysis, 51% of subjects achieved HIV-1 RNA < 400 copies/mL and 41% achieved < 50 copies/mL at Week 48Rates of response were lower among patients with baseline viral load ≥ 100,000 copies/mLGenotyping was performed on 14 subjects at the time of study discontinuation or failure. 2/14 (14%) had K65R/K, 4/14 (29%) had wild-type virus, 1/14 had M184V without TAMs (7%), 3/14 (21%) had ≥ 1 TAMs without M184V, and 4/14 (29%) had ≥ 1 TAMs with M184V. 3/14 subjects had mutations at baseline, which included V118I/V, K103N, Y188F/H/L/Y, T215A/I/S.TAMs: mutations at codons 41, 67, 70, 210, 215, and 219For more information, please go online to:204481624324048Study Week*≥ 400 copies/mL at ≥ 24 weeksCohen C, et al. ICAAC Abstract H-521. Elion R, et al. ICAAC Abstract H-1068.
23 Problemy z Didanosine + Tenofovir + Efavirenz Badanie TEDDI potwierdziło poprzednie doniesienia o większym odsetku pacjentów z niepowodzeniem wirusologicznym przyjmujących ddI + TDF + EFV VF: 25% po 12 tygodniach of TDF + ddI + EFVBadanie EFADITE pts ze stabilną supresją, którzy przestawieni zostali na TDF + ddI + EFV albo zostali na dotychczasowym leczeniu Utrzymano stłumienie wiremii u większości ptsJednak, CD4+ ↓ na TDF + ddI + EFVMedian change in CD4+ at Yr 1, -25 vs +46 in controls (P = .007)Significantly larger CD4+ declines in pts on high vs low ddI doses1. van Lunzen J, et al. IAS Abstract TuPp0306.2. Barrios A, et al. IAS Abstract WePe12.3C16.
24 Mean CD4+ Decrease (ITT) Mean Change in CD4+ Cell Count (cells/mm3) 3TC Alone vs Treatment Interruption in Patients Failing 3TC-Based HAARTMean VL Increase (ITT)Mean CD4+ Decrease (ITT)2.03TCTIWeeksP = .00154122436481.5Mean Change in HIV-1RNA (log10 copies/mL)-501.0-100Mean Change in CD4+ Cell Count (cells/mm3)-1500.5-200-250P = NS3TCTIThe aim of this study was to verify whether maintaining the M184V mutation in failing patients by continuing lamivudine alone reduces immunologic and clinical failure in comparison with complete treatment interruptionThese were relatively healthy patients with CD4 > 450 on entry, had 3TC resistance, requested treatment interruption412243648-300WeeksIn contrast to treatment interruption arm, 3TC alone resulted in:Smaller recovery in replication capacityNo further selection of resistance mutationsCastagna A, et al. IAS Abstract WeFo0204.
25 Lower Incidence of M184V/I Following Virologic Failure With FTC vs 3TC 1363 treatment-naive patients experiencing virologic failure in 1 of 3 phase III studiesFTC-301A: FTC QD + ddI + EFV vs d4T + ddI + EFVGS-903: 3TC BID + TDF + EFV vs 3TC BID + d4T + EFVGS-934: FTC QD + TDF + EFV vs 3TC BID + ZDV + EFVSignificantly ↓ rate of M184V/I emergence with FTC QD vs 3TC BID (both in combination with another NRTI and EFV)3.0P = .022.214.171.124Incidence of M184V/I in 3 Pooled Phase III Trials (%)1.53TC, lamivudine; BID, twice daily; d4T, stavudine; ddI, didanosine; EFV, efavirenz; FTC, emtricitabine; NFV, nelfinavir; TDF, tenofovir; ZDV, zidovudine.An analysis of 1363 patients who failed treatment including emtricitabine or lamivudine in 3 large phase III studies suggested that virologic failure was less likely to be associated with the M184V/I mutation in patients who received emtricitabine vs lamivudine. The reasons for this result are not clear, but may be related to the better pharmacology of emtricitabine when used in combination regimens.For more information, please go online to:1.00.60.5FTC(n = 522)3TC(n = 841)McColl D, et al. EACS Abstract PE7.3/17.
26 TOPS: Reducing Emergence of Resistance After Single-Dose NVP Arm 3Arm 2Arm 1sdNVPZDV/3TC x 4dZDV/3TC x 7dIntrapartumPostpartumMotherBabyMcIntyre JA, et al. IAS Abstract TuFo0204.
27 TOPS Update on NVP Resistance Coadministration of 4-7 days of ZDV/3TC with single-dose NVP reduced incidence of NVP resistance41/68 (60%) vs 15/135 (11%); P = .0001Study ArmNMaternal NVP Resistance*, n (%)sdNVP6841 (60%)sdNVP + ZDV/3TC x 4d678 (12%)sdNVP + ZD/3TC x 7d7 (10%)* Incidence determined by standard genotyping, which is not sensitive to minority variantsMcIntyre JA, et al. IAS Abstract TuFo0204.
28 RESIST-1 i -2: wyniki 48 tygodni 100100TPV/rCPI/rTPV/rCPI/r808052.06060Patients With HIV-1 RNA< 50 copies/mL (%)Patients With HIV-1 RNA< 400 copies/mL (%)35.8404030.422.819.614.413.82010.220ALT, alanine aminotransferase; AST, aspartate aminotransferase; CPI/r, ritonavir-boosted comparator protease inhibitor; ENF, enfuvirtide; TC, total cholesterol; TGs, triglycerides; TPV/r, ritonavir-boosted tipranavir.Tipranavir has recently been approved for the treatment of patients with multidrug-resistant HIV, particularly for patients with multiple PI resistance mutations. This approval was based on 24-week data from the RESIST trials; the 48-week results were presented at the European AIDS Clinical Society Conference. Overall, the 48-week results confirmed what was seen at 24 weeks, that ritonavir-boosted tipranavir was superior to comparator ritonavir-boosted PIs in terms of HIV-1 RNA suppression to < 50 copies/mL (left-hand figure) and < 400 copies/mL (right-hand figure).Also confirmed by the 48-week results was that the addition of a second, potent antiretroviral agent was associated with a better overall treatment response. Higher response rates were observed in patients who received enfuvirtide for the first time during the study, with 52% of patients given both ritonavir-boosted tipranavir and enfuvirtide for the first time achieving viral suppression to < 400 copies/mL. The superiority of ritonavir-boosted tipranavir over the comparator PIs was also seen in the subgroup of patients receiving enfuvirtide for the first time.No new toxicity data emerged from the 48-week analysis. The incidence of adverse events with ritonavir-boosted tipranavir was similar to that seen with the comparator PIs in all safety parameters, with 2 exceptions: more patients given ritonavir-boosted tipranavir showed elevated transaminases, and significantly elevated triglycerides and total cholesterol than in the comparator PI group. These parameters require monitoring in patients receiving ritonavir-boosted tipranavir.For more information, please go online to:n =746n = 737n = 123n = 97n =746n = 737n = 123n = 97All PatientsFirst-Time ENF UseAll PatientsFirst-Time ENF UseTPV/r similar toxicity profile to CPI/r, with 2 exceptionsElevated ALT (9.7% vs 4.2%), AST (6.1% vs 1.8%)Elevated TGs (24.9% vs 13.0%), TC (2.1% vs 0.4%)Cahn P, et al. EACS Abstract LBPS3/8.
29 Niewystępowanie oporności na PI po niepowodzeniu leczenia PI/r No primary PI resistance mutations in pts with failure of SQV/r regimenStaccato trial: Of 10 patients failing SQV/r 1600/100 mg QD + d4T/ddI (or TDF/3TC), none had primary PI mutations at failure Consistent with previous reports on FPV/r, LPV/rSOLO trial: Of 32 pts failing FPV/r + ABC + 3TC, none developed primary or secondary PI mutations at failure M trial: Of 51 pts failing LPV/r + d4T + 3TC, none had primary PI mutations at failure 1. Ananworanich J, et al. IAS Abstract WePe4.4C12.2. MacManus S, et al. AIDS. 2004;18:3. Kempf DJ, et al. J Infect Dis. 2004;189:51-60.
30 Pharmacokinetics of Dual-boosted PI Regimens Substantial reductions in APV and LPV levels previously shown when FPV and LPV/r coadministered However, new study showed no apparent adverse PK effect with ATV (300 or 400 QD) + LPV/r (400/100 BID) 20 treatment-experienced pts; 3 PI naive; 14 LPV/r naiveMedian ATV and LPV Cmin in target range69% < 400 copies/mL at Week 24Further formal drug interaction studies and clinical trials are warranted1. Kashuba A, et al. AIDS. 2005;19:2. Duvivier C, et al. IAS Abstract WePe3.2C10.
31 Nowe leki NRTIs/NtRTIs NNRTIs Entry inhibitors Protease inhibitors SPD 754 (DOTC)Amdoxovir (DAPD)D-d4FCRacivir (± FTC)SN1212Compound XNNRTIsTMC125GW (prodrug = GW695634)TMC278BILR 355 BSCSICDAPY/DATAUC781TMC120 (as microbicide)Entry inhibitorsAplavirocMaravirocVicrivirocBMSTNX-355NB-2, NB-64A total of 20 antiretroviral agents have been approved by the FDA, in 4 therapeutic classesImportant new data were presented at this meeting on a number of novel NRTIs and fusion/entry inhibitorsThese novel agents are highlighted in orange in this slide, and several will be considered in the following slidesProtease inhibitorsTMC114GW0385
32 Antiretrovirals Potentially Active in Treatment-Experienced Patients EnfuvirtideCCR5 inhibitorsTipranavirTMC114D-d4FC (NRTI)TMC125 (NNRTI)PA-457MK-0518GS-9137
33 Virologic Response to D-d4FC Randomized, dose-ranging trial of D-d4FC vs placebo in 199 experienced pts with VL > 2000 copies/mLD-d4FC active against NRTI-resistant virusesResponse to D-d4FC (200 mg QD) during initial 2-wk add-on phase0-3TAMs4-6M41L+L210WM184ValoneM184V+L74V/IK65R-0.00-0.75-0.50-0.25-1.00Change in HIV-1 RNA at Wk 2 (log10 copies/mL)Cohen C, et al. IAS Abstract WeOaLB0103.
34 Change in Plasma HIV-1 RNA (log10 copies/mL) Activity of Novel NNRTI GW695634Multicenter, double blind, randomized 7-day add-on studyN = 44 NNRTI-exp pts27 ≥ 1 NNRTI mutation at BLRemaining 17 had history of NNRTI mutationsMost common NNRTI mut: K103N, V108I, Y181CBL VL, logBL CD4+,-0.40.00.40.8-2.0-1.6-1.2-0.812345678Placebo100 mg200 mg300 mg400 mgChange in Plasma HIV-1 RNA (log10 copies/mL)Study DayBecker S, et al. IAS Abstract WePe6.2C03.
35 TMC125-C223: Virologic Response in Pts With NNRTI and PI Resistance Control (n = 40)400 mg BID (n = 80)800 mg BID (n = 79)0.4214812162024–0.19-0.4Mean (± SE) Change in HIV-1 RNA (log10 copies/mL)-0.8BID, twice daily.Results from the phase II trial of TMC125 in patients with ≥ 3 primary PI mutations showed that both doses of TMC125 were associated with a sustained 1 log10 reduction in viral load out to 24 weeks, a significantly greater reduction than the 0.2 log10 reduction seen with optimized background therapy alone. Furthermore, in patients who had no other active drugs in their regimen, the 800-mg twice-daily dose of TMC125 was associated with a 0.6 log10 reduction in HIV-1 RNA. This suggests that even in patients with NNRTI resistance mutations, this new investigational NNRTI has activity.For more information, please go online to:-1.2–1.04*–1.18*-1.6*P < .05TMC125 active in patients with no other active drugs-0.59 log10 reduction in HIV-1 RNA with 800 mg BID doseNadler JP, et al. EACS Abstract LBPS3/7a
36 POWER-2: Darunavir/r (TMC114/r) in PI-Experienced Patients Ongoing 96-week randomized trials of 3-class experienced patients 1 primary PI mutationBL HIV-1 RNA: log10 c/mLBL CD4+: cells/mm324-week data previously reported from POWER-1 cohortCurrent analysis presented 24-week data from POWER-2 cohortSame arms and entry criteria in POWER-1 and POWER-2POWER-2 Treatment ArmsDarunavir 400 mg QD +Ritonavir 100 mg QD + OBR(n = 57)Darunavir 800 mg QD +Ritonavir 100 mg QD + OBR(n = 56)Darunavir 400 mg BID +Ritonavir 100 mg BID + OBR(n = 55)BID, twice daily; BL, baseline; c/mL, copies/mL; OBR, optimized background regimen; PI, protease inhibitor; QD, once daily.For more information on the POWER-1 study, please go online to:For more information on the POWER-2 study, please go online to:Darunavir 600 mg BID +Ritonavir 100 mg BID + OBR(n = 57)Investigator-selected PI + OBR(n = 53)1. Katlama C, et al. IAS Abstract WeOaLB0102.2. Wilkin T, et al. ICAAC Abstract H-413.
37 Brecanavir (GW640385): PI Susceptibility vs Other PIs Brecanavir retains in vitro susceptibility against virus resistant to commonly used PIsIn vitro study of 55 isolates from PI-experienced patientsDrugMean IC50 (nM)Range (nM)Brecanavir1.30.1 to 14.9Amprenavir40461 to > 1500Indinavir51527 to > 1500Lopinavir44810 to 1455Nelfinavir36869 to 1309Viruses selected based on presence of protease mutations at codons 10, 32, 46, 47, 50, 54, 84, and/or 90 (mean: 8; range: 4-14)Reddy S, et al. ICAAC Abstract A-1800.
38 Brecanavir (GW640385) Novel PI Active in HIV-Infected Patients Open-label, single-arm study in HIV-infected subjectsN = 31 naive and experiencedBL VL: 4.7 log10 copies/mLBL CD4+: 311 cells/mm3Brecanavir/r 300/100 BID + 2 NRTIs77% achieved VL < 50 copies/mL at Week 24 (ITT: missing = failure)81% < 400 copies/mL at Week 246PI sensitive at BL (n = 23)PI resistant at BL (n = 6)54Median Plasma HIV-1 RNA (log10 copies/mL)3BID, twice daily; BL, baseline; c/mL, copies/mL; ITT, intent to treat; PI, protease inhibitor; VL, viral load.For more information, please go online to:2Median change at Week 24PI sensitive: -3.3 log10 c/mLPI resistant: -2.2 log10 c/mL14812162024Study WeekWard D, et al. ICAAC Abstract H-412.
39 Virologic Response to Novel Integrase Inhibitor Monotherapy MK-0518, novel integrase inhibitorActive against HIV resistant to current antiretroviralsRandomized, placebo-controlled 10-day monotherapy trial in treatment-naive patientsBL VL: log10 c/mLBL CD4: cells/mm3Good response seen with 10-day monotherapyNo dose responseAll doses generally well toleratedMK mg (n = 7)MK mg (n = 7)MK mg (n = 6)MK mg (n = 8)-3-2-11Placebo (n = 7)Change From Baseline in HIV-1 RNA (log10 copies/mL)An equally promising investigational agent that is at an earlier phase of development is the novel integrase inhibitor, MK In a randomized placebo-controlled trial of 10 days of MK-0518 monotherapy in treatment-naive patients, 4 different doses of the integrase inhibitor were studied and compared with placebo. All 4 doses of MK-0518 were associated with a significant reduction in viral load, ranging from log10 copies/mL. No significant adverse effects emerged from this phase I study, supporting its movement into phase II studies for further evaluation.For more information, please go online to:12345810Day on TherapyMorales-Ramirez JO, et al. EACS Abstract LBPS1/6.
40 MK-0518: Adverse Events Adverse events similar to placebo Serious drug-related adverse eventsAcute pancreatitis, considered secondary to OBT, n = 1Lipoatrophy, n = 1Anemia, metabolic acidosis, renal insufficiency, death, n=1Hepatomegaly, tenderness, fever (600 mg arm), n = 12 discontinuationsLack of efficacy (1); death (1)Most AEs mild to moderateGrinsztejn B, et al. CROI Abstract 159LB.
41 Integrase Inhibitor: GS-9137 10-day monotherapy studyN = 40, HIV positive, HCV/HBV negativeARV naive or experienced off treatmentRandomized 1:1 vs placeboDosing200 mg BID400 mg BID800 mg QD800 mg BID50 mg/RTV 100 mg QDPK studiesDays 1 and 10Trough sampling through Day 210.0-0.5-1.0Log10 Change HIV-1 RNAPlacebo800 QD-1.5200 BID400 BID-2.0800 BID50 + RTV QDDosing-2.5BL1234710111421DayNo serious adverse eventsOnce-daily dosing with RTV to be investigated in phase II trial with experienced patientsDeJesus E, et al. CROI Abstract 160LB.
42 Next-Generation Fusion Inhibitors Animal dataEnhanced pharmacokinetic propertiesPotential with once-weekly dosingIn vitro dataHigh genetic barrierActive against ENF-resistant virus100Cynomolgus monkey IV, 1 mg/Kg1000Clearance (mL/kg/hr) ENF TRI TRIENF10100Plasma Concentration (mm3/mL)For more information, see the Capsule Summary atFold Decrease in ActivityTRI-999TRI-999110TRI-1144TRI-1144ENF10203040123> 4Time (Hours)(n)(6)(7)(8)(9)Number of MutationsDelmedico M, et al. CROI Abstract 48.
43 Novel Maturation Inhibitor, PA-457 Podawany doustnie; 70 godzin okres półtrwania u HIV (+)Efekt leczenia koreluje z poziomem w surowicy i trough concentrationLiniowa farmakokinetyka prz różnych dawkachBadania In vitro oporności potwierdzają efekt działania studies confirm mode of actionWe wstępnych badaniach nie stwierdzono opornościFor more information, see the Capsule Summary atSmith P, et al. CROI Abstract 52.
44 TNX-355: Novel CD4+ Attachment Inhibitor Anti-CD4 monoclonal antibody blocks gp120 attachment to CD4+ receptorDelivered by IV infusionPhase II randomized trial in 82 3-class–experienced patientsTNX OBR or OBR aloneTNX-355 doses:15 mg/kg IV every 2 weeks10 mg/kg IV every week x 8 weeks, then 10 mg/kg every 2 weeksActive against R5- and X4-tropic HIVTNX OBROBR Alone15 mg/kg10 mg/kg-0.20-0.4Mean Change in HIV-1 RNA at Week 24 (log10 copies/mL)gp120, glycoprotein 120; IV, intravenous; OBR, optimized background regimen.Mean baseline viral load was slightly higher in the 15-mg/kg TNX-355 group than in the 10-mg/kg group or the placebo group (5.00 vs 4.78 and 4.83 log10 copies/mL, respectively). While 57% of patients randomized to 15 mg/kg of TNX-355 had a viral load > 100,000 copies/mL, 33% in the placebo group and 26% in the 10-mg/kg group had a viral load that high.For more information, please go online to:-0.8-0.95 (P = .003)-1.2-1.16 (P < .001)1. Norris D, et al. ICAAC Abstract LB2-26.2. Godofsky E, et al. ICAAC Abstract LB26.
45 PA-457: Virologic Response to Novel Maturation Inhibitor Monotherapy PA-457 first in new class called maturation inhibitorsTargets late step in HIV life cycleReduces viral load by disrupting production of HIV capsid protein, necessary for infecting other cellsRandomized, phase IIa study of PA day monotherapy in 32 HIV-infected patientsMedian 1 log10 VL reduction with PA mg/dayGenerally well toleratedPA-457 Dose (mg/day)PL (n = 8)25 (n = 6)50 (n = 6)100 (n = 6)200 (n = 6)+0.03+0.05-0.17 (P = .02)-0.4Median Change in HIV-1 RNA at Day 10 (log10 copies/mL)VL, viral load.For more information, please go online to:-0.48 (P = .004)-0.8(P < .0001)-1.2Beatty G, et al. ICAAC Abstract H-416d.
47 Prevalence of Metabolic Syndrome in MACS Cohort HIV-positive men more likely to have metabolic syndrome than HIV-negative menLow HDL, elevated TGs, elevated glucose more likely in HIV+Increased waist circumference less likely in HIV+Estimated Odds Ratio for HIV+ vs HIV- Pts (95% CI)P ValueMetabolic syndrome1.50 ( ).004Elevated fasting triglycerides2.81 ( )< .001Elevated fasting glucose1.81 ( )Increased waist circumference0.38 ( )Low HDL cholesterol3.15 ( )High blood pressure1.04 ( ).715Study evaluated 646 HIV-positive men and 397 HIV-negative men in the MACS cohort.Differences in components of metabolic syndrome are differences between all HIV-positive and HIV-negative patients in the MACS cohortPalella F, et al. IAS Abstract TuPe2.2B18.
48 Lipid Effects of First-line Regimens Swiss HIV Cohort Study (N = 1065; FU mos)↑ cholesterol with either PIs or NNRTIs↑ triglycerides with PIs, particularly with RTV regimensPatients primarily on LPV/r, IDV/r, or NFV↑ HDL-C with NNRTIsYoung J, et al. IAS Abstract TuPe2.2B16.
49 Dyslipidemia: Lipid-Lowering Therapy vs PI to NNRTI Switch EFVNVPPravastatinBezafibrate300250-10%-27%200Mean Total Cholesterol (mg/dL)-46%150In this Italian study published this summer, they compared the impact of substitution of a PI with the addition of lipid lowering therapy for managing dyslipidemia. The improvements in total cholesterol were statistically greater for the arms that added lipid lowering therapy compared with the switch to NNRTIs.-38%1005036912MonthsCalza L, et al. AIDS. 2005;19: TuFo0105
50 RAVE: Switch Thymidine Analogue to ABC or TDF Suppressed patients with self-defined lipoatrophy on thymidine analogue NRTI105 patients randomized to replace TA withTenofovir, orAbacavirTotal limb fat increased to similar extent in both arms over 48 weeksTDF12001061ABC10461000791800Change in Fat Mass by DEXA at Week 48 (g)600522393400316ABC, abacavir; DEXA, dual energy x-ray absorptiometry; TA, thymidine analogue; TDF, tenofovir.The Randomized Abacavir Viread Evaluation (RAVE) study examined replacing a thymidine analogue with an alternative nucleoside or nucleotide analogue. In this study, patients with self-defined lipoatrophy were randomized to replace their thymidine analogue (stavudine or zidovudine) with either abacavir or tenofovir. Both strategies were associated with similar increases in total limb fat, with no significant differences between the treatment arms, suggesting that both abacavir and tenofovir are reasonable alternatives in patients with thymidine analogue–associated fat loss.For more information, go online to:200LimbTrunkTotal FatWithin-group change in limb fat from baseline: TDF (P = .01), ABC (P = .001)Moyle G, et al. CROI Abstract 44LB.
51 No. of Patients With Events Risk of Disease Progression or Death SMART: HIV Progression by Sex and Race; Severe ComplicationsSubgroupsNo. of Patients With EventsRelative Risk (95% CI)2.5All Patients164Sex2.3Male1183.4Risk of Disease Progression or DeathFemale46Race3.6Black712.0Nonblack931.5For more information, please see the Capsule Summary atSevere Complications1141.4CVD, liver, or renal deaths311.5Risk of ComplicationsNonfatal CVD events631.4Nonfatal hepatic events142.5Nonfatal renal events70.1Favors TI1.0Favors CT10.0El-Sadr W, et al. CROI Abstract 106 LB.
52 CD4+ Cell Count–Guided TIs: Summary TI may be safe if patient has CD4+ cell count > 350 cells/mm³ and remains above that levelIn these trials, TI has led to some risk of progression and/or resistance and may potentially lead to increased risk of transmissionIn the US, if therapy is indicated, the best results are seen in patients who are on continuous therapyIn developing countries, further investigation of TI is warranted due to limited ART availabilityIn SMART, increased risk of poor outcome noted unexpectedly early in the interruption periodIn SMART, presence of viremia at baseline associated with poorer outcomes regardless of armIn viremic patients, no increased risk with CD4+-guided TI (RR 1.1)In aviremic patients, ↑ risk of progression or death with TI (RR 3.8)
53 KoinfekcjeThis section of slides is about hepatitis coinfection and opportunistic infections.
54 170-200 million carriers worldwide 10 million HIV coinfected* Hepatitis C: A Global Health Problemmillion carriers worldwide 10 million HIV coinfected*W. Europe 5 M 30-50% HIV+*E. Europe 10 MFar East 60 MUSA 3-4 M 30% HIV+*South East Asia MAfrica MAmericas MHIV40 MAustralia 0.2 MHCVMHBV350 M*HCV/HIV coinfection linked to IDUWHO
55 Increase in Sexual Transmission of HCV Great Britain; 3 cities; 111 HIV-positive MSM with acute HCVPhylogenetic analysis of 91 E1/E2 sequences indicated common source transmission of HCVRisk factors for HCV infection by case-control analysisMeeting sexual partners in bathhouses or over the InternetBody piercing or tattooingSexual partners and unsafe sex practices, including group sexRecreational drug use and drug use during sexSTDsAmsterdam Cohort Study10-fold increase in HCV since 200029 cases of HIV-positive MSM with acute HCVPhylogenetic analysis (n = 24) identified 2 clusters, which are not related to other Dutch risk groups18 reported unsafe sex practices or mucosal-damaging STDsOut of 20 surveyed, all denied IDUFor more information see the Capsule Summary at1. Danta M, et al. CROI Abstract Coutinho R, et al. CROI Abstract 87.
56 Increase in HCV RNA Detection After HAART Initiation Analysis of HCV/HIV-coinfected pts in the HOMER cohort20% of patients who were HCV-Ab (+)/HCV RNA (-) pre-HAART became HCV RNA (+) after HAARTPossible explanationsBlipsLaboratory variation, errorImmune restorationBaseline samples tested with unambiguous results(n = 1186)PCR (+): 70%(n = 425)PCR (-): 30%(n = 179)HCV Ab (+) and PCR (+) after mos of HAART: 20%(n = 24 of 118 evaluable samples)HCV-Ab (+): 51%(n = 606)HCV-Ab (-): 49%(n = 580)Braitstein P, et al. IAS Abstract TuPe1.1C30.
57 Complications in HCV/HIV-Coinfected vs HCV-Monoinfected Patients Encepha- lopathyVariceal bleedingHCV/HIV coinfectedHCV monoinfectedFrequency as First Hepatic Decompensation (%)1020304050607014%8%4%27%66%38%11%2%3%17%1%AscitesJaundiceSBPHCCHepatorenal syndromeP = .01P < .001P = NSP = .02SBP, spontaneous bacterial peritonitis; HCC, hepatocellular carcinomaMiro J. IAS Abstract TuFo0303; Pineda JA et al, Hepatology. 2005, 41:779-89
58 HCV-3 Coinfection Associated With Greater Risk of Hepatotoxicity N = 388 HIV/HCV-coinfected patients in Italian cohort132 had HCV genotype 3Factors associated with ↑ risk of grade ≥ 3 hepatotoxicityMale sexHBsAg positivityBaseline ALTHCV genotype 31.0Cumulative Proportion of Patients Free of ≥ Grade 3 HepatotoxicityHCV ≠ 126.96.36.199P < .001ALT, alanine aminotransferase; HBsAg, hepatitis B surface antigen; HCV-3, hepatitis C virus genotype 3; HCV≠3, non-hepatitis C virus genotype 3.Grade ≥ 3 hepatotoxicity defined as any increase by ≥ 5 x ULN in ALT or ASTData from other studies suggest HCV-3 associated with higher incidence of NASHFor more information, please go online to:0.6HCV-30.50.40.00.51.01.52.02.53.0Time Since Entry (Years)Torti C, et al. ICAAC Abstract H-1484.
59 Rapid Fibrosis Progression in HCV/HIV-Coinfected Patients 10091First biopsySecond biopsyMean time between biopsies: 50 months8060*All patients were F1 at second biopsy.Patients (%)40*33401820HCV, hepatitis C virus.A study by Bonnard and colleagues showed that liver fibrosis in HIV/HCV–coinfected patients can rapidly progress to cirrhosis and that coinfected patients may require more frequent liver biopsy than patients with HCV monoinfection. The investigators evaluated fibrosis stage at first and second biopsy in a cohort of HIV/HCV-coinfected patients. As shown in this slide, a significant proportion of patients with modest fibrosis (stage F2 or less) at first biopsy progressed to stage 3 or 4 fibrosis within a mean interval of only 50 months.Overall, 28% of patients progressed by 2 or more fibrosis points between biopsies. This is a greater rate of progression than one would anticipate in patients with HCV monoinfection, and suggests that specific guidelines should be developed for HIV/HCV-coinfected patients. Clearly, the clinical importance of this finding is that the morbidity of HCV infection is related to the development of fibrosis, with consequent cirrhosis of the liver and an increased risk for hepatocellular carcinoma. This will be an important consideration in future survival analyses and in regard to long-term management of HIV/hepatitis-coinfected patients.For more information, please go online to:99F0/1F2F3F4Fibrosis Stage9/32 (28%) of HCV/HIV-coinfected patients progressed ≥ 2 fibrosis points between biopsiesBonnard P, et al. EACS Abstract PE13.2/2.
60 HAART and Liver Enzyme Elevations Meta-analysis of 20 publications of HIV-infected patients ± HCV coinfectionGrade 2 or higher liver elevations noted% LEE in HCV-Coinfected Patients by Drug ClassP = .02540P = .00432.00P = .00930For more information see the Capsule Summary atPatients With LEE,%18.442015.9614.6713.62105.26NNRTIPIMixedBPINRTIOverallDrug ClassBenhamou Y, et al. CROI Abstract 88.
61 Response to Treatment During Acute HCV in HIV-Coinfected Patients 59% SVR among pts with acute HCV treated with 24 wks Peg-IFN alfa 2b + RBVSimilar to overall rate in treatment of chronic HCV in coinfected ptsBetter for genotype 1 coinfected pts vs treatment during chronic infectionLower than that with treatment of acute HCV in monoinfected ptsHigh rate of spontaneous clearance w/o therapy (24%)20406080100All Patients (n = 27)Genotype 1 (n = 20)Genotype non-1 (n = 4)67%65%100%59%55%SVRETRVirologic Response (%)Peg-IFN (1.5 g/kg/wk) + RBV ( mg/day) for 24 weeksNelson M, et al. IAS Abstract TuPe1.1C10.
62 Low Numbers of HCV/HIV Patients Achieve SVR in an Urban HIV Clinic Retrospective analysis of Johns Hopkins HIV Clinicn = 845 with HCVn = 277 referred (33%)n = 125 enteredevaluation for treatmentn = 29 initiated treatmentFor more information see the Capsule Summary atn = 6 (21%) of these attained SVRThis represents 2.1% of those referred, or 0.7% of those with HCVMehta S, et al. CROI Abstract 884.
63 Use of QuantiFERON-TB Gold in HIV-Infected Patients QuantiFERON-TB Gold, new blood-based diagnostic test for TB infectionUses peptides absent from BCG and common non-tuberculous mycobacteriaCDC recommends that QFT-G be used in all circumstances in which the TB skin test is currently usedSensitivity unknown in HIV populationEvaluated in 590 HIV-infected pts27 QFT-G positiveLimitationsNo comparison with skin testingNo means of assessing true TB infection rate100QTF-G(-) (n = 543)89QTF-G(+) (n = 27)818060Patients (%)40BCG, Bacille Calmette-Guérin; CDC, Centers for Disease Control and Prevention; QFT-G, Quantiferon-Gold; TB, tuberculosis.For more information, please go online to:QFT-G results can be available < 24 hours after testing without the need for a second visit, whereas a tuberculin skin test (TST) requires a second visit to read the result 48–72 hours after administration of the test.QFT-G, unlike TST, requires drawing blood and errors in collecting or transporting blood specimens or in running and interpreting the assay can decrease the accuracy of QFT-G.201067420-99> 300Mean CD4+ Cell Count (cells/mm3)1. Mazurek GH, et al. MMWR Morb Mortal Wkly Rep. 2005;54(RR- 15): Brock I, et al. ICAAC Abstract H-1494.
64 Hepatotoxicity with Rifampin + SQV/r 2/05 FDA letter warning of ↑ risk of hepatotoxicity when hard-gel SQV/r taken with rifampin in healthy volunteersConfirmed by data in TB/HIV-coinfected patientsProspective study of 20 coinfected patients who began SQV/RTV (400/400 BID) 30 days into TB treatment 14 pts discontinued during TB-HIV therapy phase due to ARV intolerance (mostly hepatic and gastrointestinal events)Chart review of 12 coinfected pts on rifampin who began SQV/r (1000/100 BID) + 2 NRTIs during induction phase 6 experienced hepatotoxicity3 cases moderate to severe; all had HCV1 pt permanently discontinued antiretroviral treatmentSQV and RTV AUC slightly decreased, but concentrations still in normal range1. Rolla V, et al. IAS Abstract WePe3.3C03.2. Duran A, et al. IAS Abstract TuPe7.1C22.
65 EuroSIDA: Liver-Related Deaths in HIV-Infected Patients Death rates from liver-related disease appear to have decreased in Europe ( /5)After adjusting for CD4+ cell count, small ↑ in liver disease–related deaths noted↑ HAART exposure associated with ↑ liver disease–related death after adjusting for CD4+ cell countMay be due to ARV-induced liver toxicity, progression of liver disease in HBV- or HCV-coinfected patients as patients survive longer, or other factorsARV, antiretroviral; HBV, hepatitis B virus; HCV, hepatitis C virus.An interesting analysis from the EuroSIDA cohort evaluated liver-related deaths in patients with HIV disease. Although overall death rates from liver disease decreased in Europe over the last 10 years, after adjusting for CD4+ cell count, there was a small increase in liver-related deaths. This increased risk of liver-related deaths also appeared to be associated with increased exposure to antiretroviral therapy. The reasons for this are not yet understood. The cause may be increased toxicity from antiretroviral therapy; however, it could also be due to an increase in hepatitis B and C coinfection, which is now becoming more evident as patients are living longer due to the increasing effectiveness of antiretroviral therapy. Clearly, this is an observation that requires further analysis and awareness of liver-related deaths, and highlights the importance of monitoring HIV-infected patients for liver disease.For more information, please go online to:Lundgren J, et al. EACS Abstract PS7/2.
66 Predictors of Anal Dysplasia in HIV-Positive and HIV-Negative MSM UCSD anal dysplasia screening clinicPap screening not associated with decreased prevalence of invasive anal cancer, although earlier stage at detection suggestedPap correlated with biopsy (increasingly so with increased operator experience)Anal dysplasia referral population study36% of HIV-positive men and 30% of HIV-negative men had high-grade anal dysplasiaPap results did not correlate with biopsyARV use and duration not predictive of high-grade anal dysplasiaFor more information see the Capsule Summary atResults conflict with those of Palefsky et al who suggested that receipt of HAART was associated with higher rate of anal dysplasia (Palefsky JM, et al. JAIDS. 1997;14: )1. Press N, et al. CROI Abstract Montaner J, et al. CROI Abstract 807.