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Published on January 4, 2008

Author: Carlton

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Highlights of the XIV International AIDS Conference July 7-12, 2002; Barcelona, Spain:  Highlights of the XIV International AIDS Conference July 7-12, 2002; Barcelona, Spain Selected and summarized by Joseph J. Eron, Jr, MD Associate Professor of Medicine University of North Carolina at Chapel Hill Kiat Ruxrungtham, M.D. Associate Professor of Medicine Chulalongkorn University and HIV-NAT, TRC AIDS Research Center Bangkok, Thailand Supported by an unrestricted educational grant from TRACK B Slide2:  HIV Eradication by HAART Is Impossible However, long-term suppression appears possible โอกาสหายขาดคงยังไม่มี แต่การควบคุมเชื้อระยะยวาเป็นไปได้ Viral Dynamics of HIV Infection:  Viral Dynamics of HIV Infection HIV-NAT Slide4:  Siliciano R. CROI Chicago 2001 Update: HIV Eradication by HAART Is Impossible:  Update: HIV Eradication by HAART Is Impossible Updated data from Siliciano (Johns Hopkins) One important reservoir = HIV-infected resting T cells Transcriptionally silent, so invisible to immune surveillance Unaffected by current drugs Replenished by cell division, not from viral replication Half-life is at least 6 months, so decay rate is measured in decades No decrease in decay rate in optimally treated, chronically infected patients with no “blips” of viremia Even if this reservoir could be flushed, others exist However, long-term suppression appears possible In patients with long-term suppression, virus released into circulation is wild-type No resistance even to drugs with low genetic barrier in many patients with long-term suppression Abstract: MoOr103 Impact of Evolving ARV Regimens on Virologic Responses:  Impact of Evolving ARV Regimens on Virologic Responses Time Is this the future? 1987–1991: Single nucleoside 1991–1995: Dual nucleoside 1996–today: HAART Log change in HIV RNA from baseline +Adherence Slide7:  First-line Regimens: What to Choose, What to Avoid จะเลือกสูตร HAARTอะไรดี ยังเป็นคำถามที่คำตอบมากขึ้น แต่คงเปลี่ยนแปลงไปตามเงื่อนไขเวลา ACTG 384:  ACTG 384 Head-to-Head Comparison of 6 Initial Regimens:  Head-to-Head Comparison of 6 Initial Regimens ACTG 384 Study Outline Factorial design: Zidovudine/lamivudine (ZDV/3TC) vs stavudine/didanosine (d4T/ddI) as NRTI backbones Efavirenz (EFV) vs nelfinavir (NFV) vs both as the additional agent(s) Comparison of sequential 3-drug vs single 4-drug therapy Abstracts: LbOr20A/B Head-to-Head Comparison of 6 Initial Regimens : ACTG 384 (2):  Head-to-Head Comparison of 6 Initial Regimens : ACTG 384 (2) Primary End point Time to failure after exposure to all 3 classes, ie: Time to failure of the 4-drug regimen Time to failure of the second 3-drug regimen Baseline Characteristics N = 980 72% male, 47% white Median baseline CD4+ cell count = 278 cells/mm3 Median baseline plasma HIV-1 RNA level = 4.9 log10 copies/mL Median follow-up = 28 months Head-to-Head Comparison of 6 Initial Regimens : ACTG 384 (3):  Results Factorial design thwarted by interactions between the regimen components: Activity of efavirenz differed with ZDV/3TC vs d4T/ddI Activity of ZDV/3TC differed with nelfinavir vs efavirenz In the arms receiving sequential 3-drug regimens: Time to first failure was substantially longer with ZDV/3TC/EFV Time to second failure appeared substantially longer if either the first or second 3-drug regimen was ZDV/3TC/EFV Comparing sequential 3-drug vs single 4-drug regimens: No additional benefit from receiving nelfinavir with ZDV/3TC/EFV Significantly more toxicity from d4T/ddI vs ZDV/3TC backbone No significant differences in CD4+ cell count responses Results strongly support use of ZDV/3TC/EFV as initial therapy and suggest that the ddI/d4T backbone may be suboptimal Head-to-Head Comparison of 6 Initial Regimens : ACTG 384 (3) CLASS STUDY:  CLASS STUDY CLASS Study of First-Line Regimens:  CLASS Study of First-Line Regimens Study Outline Study of antiretroviral sequencing; initial ITT analysis of 3 first-line regimens: Abacavir/lamivudine/efavirenz (ABC/3TC/EFV) Abacavir/lamivudine/amprenavir/ritonavir (ABC/3TC/APV/rtv) Abacavir/lamivudine/stavudine (ABC/3TC/d4T) Planned interim analysis at 48 weeks Baseline Characteristics N = 291 70% were black or Hispanic Mean baseline viral load = 4.19 log10 copies/mL; 42% > 100,000 copies/mL 35% had CD4+ cell counts < 200 cells/mm3 28% had CDC stage B or C disease Abstract: TuOrB1189 CLASS Study of First-Line Regimens (2):  CLASS Study of First-Line Regimens (2) Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center Plus ABC+3TC VL >100,000 Overall NNRTI bPIs NRTI NNRTI bPIs NRTI Plus ABC+3TC CLASS Study of First-Line Regimens (3):  CLASS Study of First-Line Regimens (3) Results Suppression to < 50 copies/mL highest in the efavirenz arm: 76% vs 52% (APV/RTV) and 62% (d4T); P = .047 Efavirenz also superior if baseline viral load > 100,000 copies/mL 77% < 50 copies/mL vs 53% and 55% Similar increases in CD4+ cell count 26 (9%) premature discontinuations; only 5 (2%) due to AEs 6% abacavir hypersensitivity Comments RT mutation pattern in failures with ABC/3TC backbone will be instructive Importance of regimen convenience cannot be underestimated Similar comparisons should be undertaken with more compact PIs, eg, fosamprenavir or atazanavir Patients With Advanced Disease การรักษาด้วย NNRTIs ในผู้ติดเชื้อที่มี ภูมิต่ำมากๆ จะได้ผลเพียงใด ? EFAVIP-2:  Patients With Advanced Disease การรักษาด้วย NNRTIs ในผู้ติดเชื้อที่มี ภูมิต่ำมากๆ จะได้ผลเพียงใด ? EFAVIP-2 Reassuring Data About First-line Efavirenz in Patients With Advanced Disease:  EFAVIP-2, all treatment-naive patients with baseline CD4+ cell counts < 100 cells/mm3 : 2 NRTIs + efavirenz (n = 92) vs 2 NRTIs +PI (n = 218). Median CD4+ cell count of 39 cells/mm3 at baseline, and median viral load > 250,000 copies/mL. The hazard ratios for time-to-failure were 2.92 (CI, 1.36-54.8) in an analysis adjusted for age, sex, risk group, NRTI backbone, baseline CD4+ cell count, and baseline viral load, suggesting an almost 3-fold advantage for the efavirenz group. CD4+ cell count increases in the efavirenz group was 100 cells/mm3 greater at month 24 Reassuring Data About First-line Efavirenz in Patients With Advanced Disease Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center A Thai Study: Asda Viphakul et al 2002:  50 patients with cryptococcosis treated for >4 weeks Median Baseline CD4=17, VL=5.1 log10/ml Triple ARV: d4T/3TC/EFV Results: At 24 week, 90 % showed VL <50 copies/ml, median increase in CD4 ~90 BKK Symposium 2002 and Poster Abs the XIV IAS, Barcelona 2002 A Thai Study: Asda Viphakul et al 2002 Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center Can we do better with other RTI, beside AZT or d4T as a main backbone ? จะมีตัวเลือกใดที่ดีกว่า AZT, d4T เป็นยาหลักในสูตร HAART ? Tenofovir DF: Gilead 903 study:  Can we do better with other RTI, beside AZT or d4T as a main backbone ? จะมีตัวเลือกใดที่ดีกว่า AZT, d4T เป็นยาหลักในสูตร HAART ? Tenofovir DF: Gilead 903 study Principles of ARV Combinations:  Principles of ARV Combinations + + Triple Antiretroviral Treatment 2 Nucleoside RT Inhibitors + NNRTI (EFV) /Boosted PIs Aim of Rx: Maximal HIV viral suppression for the longest duration a3TC/ddI as a back bone is also currently recommended bNVP, ABC may not effective in patients with VL>100,000/ml ddI+3TCa Tenofovir DF in Treatment-Naive Subjects:  Tenofovir DF in Treatment-Naive Subjects Study Outline Gilead 903 study: randomized, double-blind, placebo-controlled Treatment-naive subjects (N = 600) plasma HIV-1 RNA level > 5000 copies/mL (median = 81,300) any CD4+ cell count (median = 279) Randomized to initiate therapy with either: tenofovir DF (QD) and stavudine placebo (BID), or stavudine (BID) plus tenofovir DF (QD) each combined with open-label efavirenz (QD) + lamivudine (BID) Abstract: LbOr17 Tenofovir DF in Treatment-Naive Subjects:  Tenofovir DF in Treatment-Naive Subjects Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center % Patients with VL <50 copies/ml at Week 48 Slide23:  Results at Week 48 Equivalent virologic and immunologic outcomes: HIV-1 RNA < 50 copies/mL in 81% to 82% of both arms (ITT, M=F) CD4+ cell count increases of 167-169 cells/mm3 in both arms Similar rates of adverse effects: More peripheral neuropathy on stavudine Lactic acidosis: 3 on stavudine, none on tenofovir DF Triglycerides: +74 mg/dL on stavudine; no change on tenofovir DF Cholesterol: +53 mg/dL on stavudine; +25 mg/dL on tenofovir DF Question: Resistance pattern after TDF/3TC/EFV failure? Will K65R mutation appear more commonly in previously naive patients? Question: Long-term effects of regimens on metabolic parameters, eg, fat redistribution, bone density? The Gilead 903 study will remain a blinded comparative study for 3 years so many, if not all, of these questions will be answered Tenofovir DF in Treatment-Naive Subjects Protease Inhibitors (PIs) Associated With More Cardiac Events Than NNRTIs การรักษาด้วย Protease Inhibitors (PIs) มีโอกาสเสี่ยงต่อการเป็นโรคหลอดเลือดหัวใจสูง:  Protease Inhibitors (PIs) Associated With More Cardiac Events Than NNRTIs การรักษาด้วย Protease Inhibitors (PIs) มีโอกาสเสี่ยงต่อการเป็นโรคหลอดเลือดหัวใจสูง Protease Inhibitors (PIs) Associated With More Cardiac Events Than NNRTIs :  Protease Inhibitors (PIs) Associated With More Cardiac Events Than NNRTIs Study Outline Multicenter, randomized trial in Italy: 776 patients treated with a PI-containing regimen 775 patients treated with a non-PI regimen End points: new myocardial infarction or new-onset angina Baseline Characteristics Average age = 36 years Median CD4+ cell count at baseline = 325 cells/mm3 (range, 170-850) 87% smokers Follow-up After 3 years, 587 PI and 621 non-PI patients remained on original regimen Barbao et al. Abstract: WeOrB1307 PIs Associated With More Cardiac Events Than NNRTIs (2):  PIs Associated With More Cardiac Events Than NNRTIs (2) Results 23 episodes of new heart disease in PI group 6 transmural MI, 6 non-Q-wave MI, 11 new-onset or unstable angina 2 episodes of new heart disease in non-PI group 1 MI, 1 angina Highly statistically significant difference in heart disease-free survival between arms Incidence of heart disease in PI group: > 10-fold that of the non-PI group, and > 50-fold that of the general population Heart disease associated with lipodystrophy signs (OR = 26.9), elevated lipids (OR = 14.2), smoking (OR = 9.7), male sex, and HIV treatment. Non-blinded study, so the risk of an ascertainment bias (ie, cardiac events were sought more carefully in PI-treated patients) should be kept in mind Risk Factors for Progression in Naive Patients Starting HAART:  Risk Factors for Progression in Naive Patients Starting HAART Study Outline Pooled analysis of data from 12,574 patients in 13 cohort studies Intention-to-treat analysis of subjects starting 3-drug therapy, 80% with 2 NRTIs plus 1 PI Baseline characteristics: Median age = 38 years 21% CDC stage 3 disease Median CD4+ cell count = 250 cells/mm3 Mean plasma HIV-1 RNA = 4.9 log10 copies/mL Follow-up = 24,310 person-years: 870 patients experienced at least 1 AIDS event 344 died 1094 either developed AIDS or died Abstract: TuOrB1140; Lancet 2002;360:119-129. Risk Factors for Progression in Naive Patients Starting HAART (2):  Risk Factors for Progression in Naive Patients Starting HAART (2) Results Risk of progression/death at 1, 2, or 3 years estimated based on baseline CD4+ cell count, log HIV-1 RNA, age, transmission group, and CDC stage Baseline CD4+ cell count < 200 cells/mm3 associated with highest risk of progression Baseline viral load was significant only if > 5.0 log10 copies/mL Other risk factors: age > 50 years; injection-drug use; CDC stage 3 disease Viral load at month 6 of therapy was a significant factor at all levels. Comments Optimal CD4+ cell count (> 200) for therapy initiation remains unknown Factors such as age, IDU, and high viral load may weigh toward early therapy Interactive risk calculator available online: http://www.art-cohort-collaboration.org FRAM Study: Defining Lipodystrophy :  FRAM Study: Defining Lipodystrophy Study Outline Aim: Compare randomly selected HIV-infected subjects and healthy controls and identify statistically significant differences and any linkages between components of lipodystrophy Three types of evaluation: Self-report re: body habitus changes Clinical evaluation of presence/degree of visible lipoatrophy Body composition measures including whole-body MRI and DEXA scanning N = about 1200 HIV-infected subjects from 16 US clinics and 300 controls Subjects and controls were well matched for baseline characteristics, but subjects were lighter than controls This report focused on only a subset of enrolled men, not all subjects Abstract: TuOrB1140 FRAM Study: Defining Lipodystrophy (2):  FRAM Study: Defining Lipodystrophy (2) Initial Results Subjects were more likely to have lipoatrophy when compared with controls, by all 3 measures Nonuniform pattern of subcutaneous lipoatrophy: Loss from legs > arms > lower trunk > upper trunk Visceral adipose tissue non-significantly lower in subjects vs controls No linkage between changes in amounts of subcutaneous vs visceral fat No significant difference in prevalence of “buffalo hump” in subjects vs controls Rates of accumulation of visceral fat or “buffalo hump” fat could not be compared in this cross-sectional study Discontinuing HAART in Prematurely Treated Patients การหยุดยา HAART ในผู้ติดเชื้อ HIV ที่เริ่มการรักษาเร็วเกินไป จะปลอดภัยไหม ?:  Discontinuing HAART in Prematurely Treated Patients การหยุดยา HAART ในผู้ติดเชื้อ HIV ที่เริ่มการรักษาเร็วเกินไป จะปลอดภัยไหม ? Discontinuing HAART in Prematurely Treated Patients:  Discontinuing HAART in Prematurely Treated Patients Study Overview Views on initiating HAART have recently become more conservative: many patients now on treatment would not have met current criteria for starting Should such patients discontinue HAART? Johns Hopkins cohort of patients who interrupted HAART N = 101 44% “prematurely treated”; 30% toxicity/nonadherence; 8% virologic failure HAART resumed if CD4+ cell count < 200 cells/mm3 or by physician/patient decision Abstract: ThOrB1439 Discontinuing HAART in Prematurely Treated Patients (2):  Discontinuing HAART in Prematurely Treated Patients (2) Predictors of Successful Interruption 33/101 patients resumed HAART: 25% had rising HIV-1 RNA; 24% had falling CD4+ cell count; 24% had both Resumers had lower mean CD4+ cell count and less viral suppression at time of interruption Pre-HAART CD4+ cell count (but not viral load) was strongest predictor of duration of interruption: 7-fold greater likelihood of resumption if pre-HAART CD4+ cell count < 200 cells mm3 (P = .001), compared with pre-HAART baseline CD4+ cell count > 500 cells/mm3 4-fold greater likelihood if pre-HAART CD4+ cell count = 200-350 cells/mm3 (P = .015) Patients who met current guidelines for therapy at time of interruption were 3-fold more likely to resume therapy than those who did not (P = .004) Proportion Remaining off HAART:  Baseline CD4 >350 Baseline CD4 <350 Proportion Remaining off HAART ~ 40% ~ 80% 0 1 2 3 Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center Can we switch from protease inhibitor(PI)-based therapy to the others ? การเปลี่ยนสูตรจาก Protease inhibitor เป็นสูตรอื่น จะได้ผลดีแค่ไหน ? Switch Studies :  Can we switch from protease inhibitor(PI)-based therapy to the others ? การเปลี่ยนสูตรจาก Protease inhibitor เป็นสูตรอื่น จะได้ผลดีแค่ไหน ? Switch Studies Switch Studies:  Switch Studies In a large prospective, randomized trial Patients with plasma HIV-1 RNA levels < 200 copies/mL were switched from protease inhibitor(PI)-based therapy to either nevirapine, efavirenz, or abacavir.[4] N= 460 evaluable patients In an intent-to-treat (ITT) analysis at 12 months Martinez E 2002 Abstract WeOrB1262 Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center Switch Studies : ITT analysis:  Switch Studies : ITT analysis Characteristic Nevirapine Efavirenz Abacavir P value N 155 156 149 % VL < 200 78% 74% 77% ns CD4+ increase 41 51 51 ns Discontinuations 16% 17% 6% .009 due to AEs Cholesterol 24% 22% 9% .01 > 240 mg/dL Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center Martinez E 2002 Abstract WeOrB1262 HIV Drug Resistance ปัญหาเชื้อดื้อยา: ต้องป้องกันจริงจังและคอยเฝ้าระวัง:  HIV Drug Resistance ปัญหาเชื้อดื้อยา: ต้องป้องกันจริงจังและคอยเฝ้าระวัง Drug Resistance Testing:  Drug Resistance Testing Genotypic Assay -To detect specific mutations in HIV-1 RT and protease genes Phenotypic Assay -Measure the 50% or 90% inhibitory concentration (IC50 or IC90) for a drug by recombinant virus assay Modified from Hirsch M et al JAMA 2000 Transmission of Resistant HIV Prevalence in Primary HIV infection:  Transmission of Resistant HIV Prevalence in Primary HIV infection U.S. cohort 10 cities (1997-2000) = 7 % Spain cohort (1996-2001) = 9 % Prevalence of HIV Drug Resistance in Naive Patients Brazil Surveillance Brazil :Patients treated with HAART >120,000 Surveyed 224 treatment naive patients 1.9 % NRTI resistance 3.9 % NNRTI resistance 1.3 % PI resistance Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center NRTI Resistant Mutations:  NRTI Resistant Mutations MDR 41 67 70 210, 215, 219 AZT d4T 69S NAMs 151 IAS-USA update Dec 2001 151 complex 69 insertion 41 67 70 210, 215 , 219 AZT d4T 69S 151 Resistant HIV in ART failing Patients:  Resistant HIV in ART failing Patients Thailand, Sirivichakul et al : Dual NRTI failure 119 cases 92 % NAMs (codons 41, 67, 70, 210,215, 219 mutations) 70% 3TC-R (M184V) MDR: 4% Q151M, 2.5 % T69 insertion Canadian cohort (N=991): 80% 3TC and NNRTI-resistance, 60% PI-resistance Predictors of successful salvage therapy: 1). >3 New drugs chsnges, 2). Mutaions <5 codons 3). Viral load at the time of resistance detected Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center Patterns of NAMs Among Thais who failed NRTIs:  Patterns of NAMs Among Thais who failed NRTIs N=133 Kiat Ruxrungtham et al 2002 New Drugs: Old and New Targets ยาใหม่: มีความหวัง ยาน่าจะดีขึ้น แต่อย่าลืมทำปัจจุบันที่มีอยู่ให้ดีที่สุด:  New Drugs: Old and New Targets ยาใหม่: มีความหวัง ยาน่าจะดีขึ้น แต่อย่าลืมทำปัจจุบันที่มีอยู่ให้ดีที่สุด Slide45:  Major Targets of Antiretroviral Agents HIV RNA DNA ds DNA RT Integrase Transcription Proviral DNA Spliced mRNA mRNA Genomic RNA Polyprotein Protein Protease Protease Inhibitors SQV,RTV, IDV, NFV, AMV, LPV/rtv RT Inhibitors NRTI: AZT, ddI, ddC, d4T, 3TC, ABC NNRTI: NVP, DLV, EFV NTRTI: Tenofovir 1 2 3 4 5 6 Entry Inhibitors CXCR4: AMD3100, T22 CCR5: SCH-C, D; TAK779 Fusion gp41: T20 vpr New Drugs in the Pipelines:  New Drugs in the Pipelines New Drugs in old classes NRTIs =8 NNRTIs =8 PIs =5 New Drugs, New Targets Entry inhibitors: 4 cadidates T20 (fusion inhibitor), SCH-C (CCR5 inhibitor), PRO542 (CD4 binding ihibitor-MAb), AMD3100 (CXCR4 inhibitor) Integrase inhibitors: 3 cadidates, preclinical studies were done, phase I has been started Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center T-20: Phase 3 Studies in Highly Experienced Patients:  T-20: Phase 3 Studies in Highly Experienced Patients Study Outline Two studies: TORO 1 (Americas) and TORO 2 (Europe and Asia) Highly treatment-experienced subjects: Median 7.4 yrs prior therapy 75% prior AIDS-defining illness Median plasma HIV-1 RNA >100,000 copies/mL Median CD4+ cell count ~ 100 cells/mm3 Over 600 subjects, randomized to change therapy to either: New regimen optimized by genotype or phenotype, or Optimized regimen plus T-20 Primary end point: change in plasma HIV-1 RNA 24 weeks follow-up Abstracts: LbOr19A/B T-20: Phase 3 Studies in Highly Experienced Patients (2):  T-20: Phase 3 Studies in Highly Experienced Patients (2) Results at Week 24 Significantly greater CD4+ cell count increases in the T-20 arms Injection-site reactions were the most frequent AE on T-20, although overall discontinuation rates between treatment arms were similar Opportunistic Fungal Infections: Safety of Discontinuing Prophylaxis?:  Opportunistic Fungal Infections: Safety of Discontinuing Prophylaxis? Two studies addressed maintenance therapy for cryptococcal meningitis. The first study was a prospective study from Thailand (Vibhagool A et al) The second study was a retrospective cohort of 56 patients from European, US, and Latin American centers. (Mussini C et al) Conclusion: Patients with invasive fungal infections whose CD4+ cell counts recover to at least 100 cells/mm3 can discontinue maintenance therapy. Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center Same-Clade Superinfection: Research and Health Implications:  Same-Clade Superinfection: Research and Health Implications Case Report Anecdotal case described by Bruce Walker (Mass Gen) Subject enrolled in primary infection study: Early initiation of HAART followed by sequential STIs Detailed longitudinal virologic and immunologic evaluations Evidence of Superinfection Subject initially controlled replication off-therapy for several months after final STI Subject had HIV-1-specific cytotoxic T lymphocytes directed at multiple epitopes Viral load increased after 1 month Genotyping indicated acquisition of a clade B virus that appeared genetically distinct from original infecting virus Patient admitted episode of unprotected sex No immunologic control of new virus; patient declined clinically despite some shared CTL epitopes between the initial and probable superinfecting HIV-1 variants Abstract: WeOrA197 Same-Clade Superinfection: Research and Health Implications (2):  Same-Clade Superinfection: Research and Health Implications (2) Implications Immune responses that were able to control initial strain could not prevent acquisition or control replication of a closely related second strain Alarming implications for vaccine research, currently focused on generating HIV-specific immune responses Superinfection with different HIV strains appears possible Superinfected strain may be more pathogenic/drug-resistant Reinforces importance of prevention counselling of infected patients Low-Cost Technologies for Diagnosing and Monitoring HIV-Infected Patients in Resource-Poor Settings:  Low-Cost Technologies for Diagnosing and Monitoring HIV-Infected Patients in Resource-Poor Settings Rapid Antibody Tests Clinical Markers of HIV Disease Stage Alternatives to CD4+ Cell Count Less Expensive Techniques for Measuring CD4+ Cell Count Virologic Assays Evaluation of an Ultrasensitive p24 Antigen Assay: Diagnosis, monitoring ? Charles Van der Horst, MD Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center The chase of affordable and portable assays for all the necessary laboratory measures:  The chase of affordable and portable assays for all the necessary laboratory measures Rodriguez et al Using microchip technology in which agarose microbeads covalently coated with molecules to detect HIV antibodies, HIV RNA, CD4, and p24 antigen are placed in the wells of stamp-sized microchips, they presented data on the detection of the antibodies and the antigen. Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center Access to Care: Reality ?:  Access to Care: Reality ? Joep Lange : "There is actually very little evidence that laboratory monitoring prevents mortality due to drug toxicity, but there is an awful lot of evidence that not treating symptomatic HIV infection is lethal, and usually not in a nice way; why are we always more concerned about doing harm than about not doing good?" Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center Slide55:  Current Ultimate Goal of HAART Relative Levels Months Years After HIV Infection CD4+ T-cells Plasma HIV Viremia Acute HIV infection Symptom Limit of detection A case study: SS on HAART (>5 years):  A case study: SS on HAART (>5 years) CD4 count (cells/mm3) Plasma HIV-RNA (copies/ml) AZT/ddI/NFV AZT/ddI/EFV Lipodystrophy VL <50 CHULA MRC Access to Care: Reality ? Scaling up Access to Therapy :  Access to Care: Reality ? Scaling up Access to Therapy Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center Scaling up Access to Therapy:  Scaling up Access to Therapy It is important to move forward on all fronts at the same time; namely: training of health professionals including doctors, nurses, pharmacists, and laboratory technicians; funds for the purchase of medications at access prices; and better, cheaper laboratory monitoring. Kiat Ruxrungtham, M.D. Chulalongkorn University and HIV-NAT, TRC AIDS Research Center

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