Second HIV Infection and the Central Nervous System: Developed and

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Second HIV Infection and the Central Nervous System: Developed and Resource-Limited Settings & Evolving Mechanisms of HIV Neuropathogenesis in the HAART era: Domestic and Global Issues 14 · 16 April, 2007 Venice - San Servolo Island · Italy © Copyright 2007 by Edizioni Internazionali srl Divisione EDIMES - Edizioni Medico-Scientifiche - Pavia Via Riviera, 39 - 27100 Pavia Tel. 0382.526253 r.a. - Fax 0382.423120 e-mail: edint.edimes@tin.it Tutti i diritti sono riservati.

Nessuna parte può essere riprodotta in alcun modo (compresi i microfilm e le copie fotostatiche senza il permesso scritto dell 9editore) EDIZIONI INTERNAZIONALI srl Edizioni Medico Scientifiche - Pavia Program APRIL 14 " SATURDAY Second HIV Infection and the Central Nervous System: Developed and Resource-Limited Settings 9.00 amWelcome and Introduction A. Lazzarin (Milan, Italy) · L. Pellegrini (Rome, Italy) SESSION 1 Treatment Implementation in Resource-Limited Settings Chair: L.

Minoli (Pavia, Italy) · K. Robertson (Chapel Hill, USA) 9:30 am01. Lecture: Evolving Changes in Treatment Implementation page 11 in Resource Poor Countries S.S.

Abdool Karim (Congella, South Africa) 10:00 am02. Antiretroviral Therapy Administration and Adherence 12 D. Bangsberg (San Francisco, USA) 10:20 am03.

Laboratory Monitoring of HIV Infection and Efficacy of Antiretroviral Treatment 13 E.M. Dax (Victoria, Australia) 10:40 am04. Pharmacoeconomics and Antiretroviral Therapy ... more. less.

Rollout in Brazil 14 A. Penalva de Oliveira (San Paolo, Brazil) 11:00 am05. Pharmacoeconomics and Antiretroviral Therapy Rollout in Africa 15 C. Merry (Dublin, Ireland) SESSION 2 Epidemiology of HIV-Associated Central Nervous System (CNS) Disease in Resource-Limited Settings Chair: V. Colizzi (Rome, Italy)· J.M. Mirò Meda (Barcelona, Spain) 11:40 am06. Lecture: Global Epidemiology of HIV Infection and AIDS 17 G. Rezza (Rome, Italy) 12:00 pm07. Epidemiology of HIV CNS Disease in Sub-Saharan Africa 18 J. Hakim (Harare, Zimbawe) 12:20 pm08. Epidemiology of HIV CNS Disease in Brazil and South America 19 J. Vidal (San Paolo, Brazil) 12:40 pm09. Epidemiology of HIV CNS Disease in India 20 M. Gathe (Pune, India) 1:00 pm10. Antiretroviral Therapy Rollout in China 21 F.J. Zhang (Beijing, China) 3 SESSION 3 Clinical Issues of HIV-Related Central Nervous System Disease in Resource-Limited Settings Chair: E. Ekong ( Lagos, Nigeria) · E. Wright (Melbourne, Australia) 2:20 pm11. HIV Dementia and Cognitive Impairment in Resource-Limited Settings page 23 N. Sacktor (Baltimore, USA) 2:40 pm12. Central Nervous System Tuberculosis 24 G.E. Thwaites (Ho Chi Min City, Vietnam) 3:00 pm13. HIV, the Central Nervous System and Stroke 25 J. Heikinheimo-Connel Terttu ( Blantyre, Malawi) 3:20 pm14. HIV and Microbial Coinfections in the Central Nervous System 27 S. de Almeida (Curitiba, Brazil) 4:00 pm OPEN PRESENTATIONS Chair: P. Ferrante (Milan, Italy) · V. Tozzi ( Rome, Italy) 4:00 pm15. Cerebral Toxoplasmosis in Jakarta 33 D. Imran, H. Khosama, J. Jannis (Jakarta, Indonesia) 4:15 pm16. Associated Factors toIn-Hospital Mortality and Long-Term Survival in Brazilian HIV-Infected Patients with Tuberculous Meningitis in the HAART era 34 M.G. Croda, J.E. Vidal, A.C. Penalva de Oliveira (San Paolo, Brazil) 4:30 pm17. Coinfection with Human T-CellLymphotropic Virus and Human Immunodeficiency Virus: Preliminary Results of a big Cohort from Rio de Janeiro, Brazil 35 M.T.T. Silva, M.J. Andrada-Serpa, E.B. Braga, D.P. Campos, H. Hojas, B. Grinsztejn, R.C. Harab, M.S. Oliveira, A.C.C. Leite, M.A. Lima, A. Araújo (Rio de Janeiro, Brazil) 4:45 pm18. Presence of Tropical Spastic Paraparesis/HTLV-Associated Myelopathy (TSP/HAM) Diagnosis among HIV-1/HTLV-II-Coinfected Subjects in São Paulo City 36 P. Montanheiro, I. Olah, L.M.I. Fukumori, M.P. Vergara, J. Smid, A.C. Penalva de Oliveira, A.J.S. Duarte, J. Casseb (San Paolo, Brazil) 5:00 pm19. Impact of Access to Care on the Neurodevelopment of HIV-Infected Children in a Resource Poor African Setting 37 A. Van Rie, A. Mupuala, A. Dow, N. Kilese , I. Zephyrin, N. Nossa (Chapel Hill, USA and Kinshasa, Democratic Republic of Congo) P01. Limitations of Diagnosis of CNSInfections in HIV Cases in Fiji Islands 29 K. Kishore, S.T. Ali (Fiji) 4 P02. HIV Positive Patients from the Asia Pacific Region who Receive NeuroHAART are less likely to have HIV-Related Neurocognitive impairment: Findings of the Asia Pacific NeuroAIDS Consortium (APNAC) Study 30 L. Lal, E. Wright, B. Brew , A. Arayawithchanont, K. Robertson, K. Samintarapunya, S. Kongsaengdao, M. Lim, S. Vonthanak, C. Sarim, S. Huffam, P. Li, D. Imran, J. Lewis, W.H. Lun, A. Kamarulzaman, G. Tau, S. Ty Ali, K. Kishore, M. Bain, R. Dwyer, G. McCormack, M. Hellard, C. Cherry, J. McArthur, S. Wesselingh SPECIAL SESSION Institutional Programs for International HIV/AIDS Research Chair: F. Castelli (Brescia, Italy) · J. Joseph (Bethesda, USA) 5:15 pm20. International Programs on HIV Infection at Fogarty International Center 39 J. McDermott (Bethesda, USA) 5:35 pm21. Added Value of International Cooperation in AIDS and Emerging Infectious Diseases 40 G. Ippolito (Rome, Italy) APRIL 15 " SUNDAY SESSION 4 Clinical Issues of NeuroAIDS in Developed Areas Chair: K. Khalili ( Philadelphia, USA) · E. Marchioni ( Pavia, Italy) 8:30 am22. Overview on Opportunistic Infections of the Central Nervous System 41 A. Ammassari (Rome, Italy) 9:00 am23. Cryptococcosis of the Central Nervous System: Classical and Immune-Reconstitution Disease 26 S. Sungkanuparph ( Bangkok, Thailand) 9:20 am24. The Pathology of Central Nervous System Immune Reconstitution Disease 43 F. Gray (Paris, France) 9:40 am25. Central Nervous System Immune Reconstitution: Role of Magnetic Resonance Imaging in Diseases Definition 46 S. Gerevini (Milan, Italy) 10:00 am26. Potential Mechanisms of Central Nervous System Immune Reconstitution Disease 47 A. Nath (Baltimore, USA) P03. Polymorphic Immune Reconstitution Inflammatory Syndrome (IRIS) after Initiation of HAART in HIV-Infected Patients 48 F. Moretti, S. Casari, F. Ceresoli, M.C. Uccelli, G. Zollo, G. Carosi (Brescia, Italy) 5 P04. Neurological Manifestations and Survival in a Cohort of HIV-Infected Patients in era HAART 49 F. Moretti, S. Casari, F. Ceresoli, G Zollo, P. Locatelli, G. Cristini, G. Carosi (Brescia, Italy) P05. A Prospective Cohort Study in JCV and non JCV-Related Leukoencephalopathies in HIV Patients: Clinical and MRI Findings 50 E. Tavazzi, P. Ferrante, G. Poloni, R. Maserati, L. Minoli, S. Del Bue, A. Pichiecchio, S. Bastianello, E. Marchioni (Milan, Italy) ROUND TABLE The Known Unknowns of Progressive Multifocal Leukoencephalopathy (PML) Chair: P. Cinque (Milan, Italy) · D. Clifford (St. Louis, USA) 10:40 am27. Virus-Host Relationship in PML 51 I.J. Koralnik (Boston, USA) 11:10 am28. New Pathogenetic Models for PML 52 K. Khalili (Philadelphia, USA) 11:30 am29. Identification of Markers of Progressive Multifocal Leukoencephalopathy Clinical Evolution: Molecular Characterization of JC Virus Genome Isolated in Cerebrospinal Fluid of HIV+ and HIV 3 PML Patients 53 S. Delbue, E. Branchetti, R. Maserati, E. Marchioni, E. Tavazzi, P. Ferrante (Milan, Italy) 11:50 am30. Predictors of Outcome inImmune-Reconstitution PML and PML Occurring in HAART-Untreated Patients 54 A.M. Pazzi, P. Costenaro, S. Casari, A. Boschini, D. Bertelli, C. Mussini, S. Sala, A. Bestetti, S. Bossolasco, A. Lazzarin, P. Cinque (Milan, Italy) P06. JCV-DNA Level in Plasma for Diagnosis and Prediction of HIV-Related Progressive MultifocalLeukoencephalopathy 57 S. Sala, A. Bestetti, A.M. Pazzi, S. Bossolasco, P. Costenaro, A. Lazzarin, P. Cinque (Milan, Italy) P07. A Case of Relapse of Progressive Multifocal Leukoencephalopathy (PML) in an HIV-Infected Patient 58 A. Pazzi, S. Sala, S. Gerevini, V. Pietropaolo, A. Bestetti, M. Mischitelli, S. Bossolasco, A. Lazzarin, P. Cinque (Milan, Italy) SESSION 5 HIV, the CNS and Antiretroviral Treatment - Part I Chair: C.F. Perno ( Rome, Italy) · R.W. Price (San Francisco, USA) 2:30 pm31. HIV Infection and the Effects of Antiretroviral Drugs in Macrophages 59 K. Williams (Boston, USA) 2:50 pm32. Central Nervous System Involvement in Primary HIV Infection 60 S. Spudich (San Francisco, USA) 6 3:10 pm33. Virus Compartmentalization and Trafficking through the Central Nervous System 61 G. Shnell ( Chapel Hill, USA) HIV, the CNS and Antiretroviral Treatment - Part II Chair: G. Arendt ( Dusseldorf, Germany) · C. Hall(Chapel Hill, USA) 4:00 pm34. Sub-Clinical Atherosclerosis andRisk of Cerebrovascular Disease 62 J.S. Currier (Los Angeles, USA) 4:20 pm35. Neuropenetration and Efficacy of Antiretroviral Therapy in the Central Nervous System 63 S. Letendre (San Diego, USA) 4:40 pm36. Immune Activation and the Disproportionate Effect of Antiretroviral Treatment on Cerebrospinal Fluid HIV 64 R.W. Price (San Francisco, USA) 5:00 pm Closing Remarks A. Antinori (Rome, Italy) P. Cinque (Milan, Italy) P08. HIV Associated Dementia along with Side Effects of the Antiretroviral Treatment in Giurgiu County 32 L. Manolescu, P. Marinescu (Romania) P09. Plasma Cerebrospinal Fluid HIV-1 RNA Dynamics are Note Parallel in SubjectsReceiving a Long Time HAART 65 N. Abrescia, M. Figoni, A. Maddaloni, A. Busto, M. D 9Abbraccio, G. Di Nicuolo, M.G. Guida, M. De Marco, G. Molinaro, C. Marrone (Naples, Italy) P10. What Correlation between Plasma and CFS HIV-1 RNA Levels in Patients with Acute Neurological HIV-1 Events? 66 N. Abrescia, M. Figoni, A. Maddaloni, A. Busto, M. D 9Abbraccio, G. Di Nicuolo, M. De Marco, M.G. Guida, G. Molinaro, C. Marrone (Naples, Italy) P11. Dopamine Metabolism Irritation as a Pace-Maker of HIV-Associated Dementia - Clinical, Neurochemical and SPECT Findings 67 G. Arendt, T. Nolting, E. Koutsilieri, I.-W. Husstedt, M. Maschke, S. Sopper, C. Antke P12. Adverse Effect of DDI, DDC and D4T asComponent of HAART on Cognitive Function during HIV-Infection 68 I.W. Husstedt, K. Biehl, N. Gregor, D. Reichelt, S. Evers P13. Antiretroviral Treatment reduces Increased CSF Neurofilament Protein (NFL) in HIV1 Infection 69 Å. Mellgren, R.W. Price, L. Hagberg, L. Rosengren, B.J. Brew, M. Gisslén 7 P14. Neuropsychological Deficits in HIV-Patients and Cytokine Levels in Cerebrospinal Fluid 70 T. Nolting, A. Lindecke, E. Koutsilieri, M. Maschke, I.-W. Husstedt, S. Sopper, H.-P. Hartung, G. Arendt P15. HIV-1 Infection of Neural Progenitor Cells 71 I. Rothenaigner, S. Kramer, M. Ziegler, H. Wolff, R. Brack-Werner P16. Amyloid Beta-Peptide Potentiates HIV-1 TAT-induced Inflammatory Gene Expression in Brain Endothelial Cells 72 M. Toborek (Lexington, USA) P17. Tobacco Smoking and Cognitive Function in HIV-Seropositive Women 73 V. Wojna, L. Robles, R.L. Skolasky, R. Mayo, O. Selnes, T. de la Torre, E. Maldonado, A. Nath, L. Meléndez, J. Lasalde-Dominicci P18. Undetectable CSF Neurofilament Light Chain (NFL) Concentration is a Marker of Inactive AIDS Dementia 74 B.J. Brew, L. Pemberton, P. Cinque, R.W. Price, L. Rosengren, L. Hagberg, M. Gisslen APRIL 16 " MONDAY Evolving Mechanisms of HIV Neuropathogenesis in the HAART era: Domestic and Global Issues 8:00 amWelcome and Introduction J. Joseph (Bethesda, USA) 8:10 am37. Plenary Talk: The Changing Phenotype of HIV Dementia in the HAART era: Potential Mechanisms 75 J. McArthur (Baltimore, USA) SESSION 1 Mechanisms of neuropathogenesis - Part I Chair: I. Grant (San Diego, USA) 8:40 am38. The Shifting Patterns of HIV Encephalitis Neuropathology 76 E. Masliah ( San Diego, USA) 9:00 am39. HIV Infection and Dementia in Older Adults: Overview 77 V. Valcour (Honolulu, USA) 9:20 am40. Brain Deposition of Beta-Amyloid in HIV Positive Patients 78 C. Achim (Pittsburgh, USA) 9:40 am41. HIV Hijacks the Proteasome: Implications for Altered Synaptic Transmission 79 B. Gelman (Galveston, USA) 10:00 am42. Changing Monocyte Phenotype on HAART: Implications for Central Nervous System Infection 80 L. Pulliam (San Francisco, USA) 8 SESSION 2 Viral and host genetics Chair: J. Berman (Bronx, USA) 10:50 am43. HIV Env Variants and Association with BrainInfection andDementia 81 D. Gabuzda (Boston, USA) 11:10 am44. Host Genetic Factors regulating HIV-CNS Disease 82 S. Ahuja (San Antonio, USA) 11:30 am45. Global CladeDiversity and HIV-CNSDisease: Overview 83 R. Ellis (San Diego, USA) 11:50 am46. Subtype-SpecificDifferences in HIV Associated Dementia: Delineating the Viral Determinants 84 V. Prasad (Bronx, USA) 12:10 pm47. HIV LTR Regulation across the Clades: Global Relevance to NeuroAIDS 85 B. Wigdahl (Philadelphia, USA) 12:30 pm48. West Africa NeuroAIDS Consortium 86 D.B Clifford, V. Prasad, A. Jaye, O. Nash, A. Ogunniyi, A. Gallo-Diop, E. Ekong, J. Idoko, K. Robertson, A. Abimiku, G. Kanmogne, M. Nunn, J. Joseph (Bethesda, USA) SESSION 3 Mechanisms of Neuropathogenesis - Part II Chair: A. Nath (Baltimore, USA) 2:30 pm49. Novel Cerebrospinal Fluid Biomarkers in the HAART era 87 M. Gisslen (Goteborg, Sweden) 2:50 pm50. Neuroimaging of Evolving White Matter Damage: Effects on Cognition in HIV and Hepatitis C Virus 88 T. Jernigan (San Diego, USA) 3:10 pm51. Mechanisms of Hepatitis C Associated Neurocognitive Impairment 89 T. Laskus (Phoenix, USA) 3:30 pm52. Mitochondrial Haplogroups and Peripheral Neuropathy during Antiretroviral Therapy 90 D. Haas (Nashville, USA) 3:50 pm53. Host Response and Dysfunction in Central Nervous System during Chronic SimianImmunodeficiency Infection 91 H. Fox (La Jolla, USA) 4:30 pmDISCUSSION: Priorities for Future Research Chair: I. Grant (San Diego, USA) 5:30 pm Closing Remarks J. Joseph (Bethesda, USA) M. Nunn (Bethesda, USA) 9 SESSION 1 01. EVOLVING CHANGES IN TREATMENT IMPLEMENTATION IN RESOURCE POOR COUNTRIES S.S. Abdool Karim Centre for the AIDS Programme of Research in South Africa (CAPRISA) University of KwaZulu-Natal and Columbia University, Congella, South Africa The Durban AIDS Conference in 2000 was a landmark in the global response to the AIDS pandemic. It created a unique juxtaposition between scientific advances, community aspi- ration, global inequity and stark reality of one of the worst affected areas in the world. With its inescapable political pressure, it cbroke the silence d resulting in the birth of a so- cial movement with a common purpose and vision for affordable AIDS treatment. The Dur- ban AIDS Conference changed the discourse from cwhether d to chow d to provide antire- troviral therapy (ART) in resource-constrained settings, especially in Africa. Since then, the collective efforts of activists, researchers, service providers, pharmaceutical companies, po- licy makers and international agencies have generated real momentum in scaling up AIDS treatment and prevention across the globe, with special emphasis on Africa. Coverage of ART in the developing world has more than doubled 3 increasing from 400 000 in 2003 to approximately 1 million by June 2005. While still short of the WHO goal of c3 by 5 d, the momentum in expanding treatment access is a remarkable achievement despite the initial challenges in implementing AIDS treatment programs, especially in Africa where the burden is largest, which included the costs of the drugs, concerns about adherence, and inadequate infrastructure for laboratory monitoring. Affordability of ART is no longer a major stumbling block to treatment access. There have been drastic declines in the price of first line antiretroviral drugs for adults, e.g. in South Africa, Efavirenz, 3TC and Stavudine (d4T), three commonly used first line agents, cost $568 (R3411) per month in 2000 compared to the current price of $51 (R307) per month. The concerns about adherence in Africa, which emanated from pre-conceived notions about low education and literacy levels and knowledge of time-keeping, have been shown repeatedly to be unfounded by ART rollout programmes in the resource constrained set- tings such as Malawi, South Africa and Uganda which have all reported very high adheren- ce levels. A major advance in easing the burden of laboratory monitoring is the widespread availabi- lity of rapid HIV tests. Since specialised costly equipment is needed to perform CD4 cell count and viral load assays, these tests are not as readily available and remain expensive. Alternative approaches to laboratory monitoring of ART with white blood cell counts and clinical status are used to supplement the sparing use of these expensive assays. Indeed, the costs of the laboratory monitoring assays are rapidly replacing the costs of drugs as the ma- jor economic impediment to ART access. With an increasing number of patients on ART, one of the main challenges faced in sustai- ning ART provision in resource constrained settings include overburdened health care servi- ces, which is further compounded by the intensive one-on-one approach to voluntary coun- selling and testing (VCT). The expansion of AIDS care is being hampered by the bottleneck created by the inability to implement large scale VCT. Rapid expansion of ART provision ne- cessitates a re-think in the paradigm of VCT provision and countries like Botswana are al- ready implementing alternative approaches, such as copt-out d testing. While the various practical and political challenges in ART provision have changed over the last 6 years, two over-arching challenges, the persistence of stigma and the failure to inte- grate prevention into care, continue to hamper the effort to maximise the benefits of ART implementation in Africa. 11 SESSION 1 02. ANTIRETROVIRAL THERAPY ADMINISTRATION AND ADHERENCE D.R. Bangsberg University of California, EPI Center, San Francisco, San Francisco, California, USA Public health debates about providing HIV antiretroviral therapy to impoverished HIV+ po- pulations are based on the relationship between adherence and risk of drug resistance to HIV antiretroviral therapy. Early justifications for withholding antiretroviral therapy from marginalized domestic populations, such as drug users and the homeless, were mistaken for two reasons. First, levels of adherence in marginalized populations were not much dif- ferent than the general HIV+ population, and second, early single protease-based antiretro- viral therapy lead to drug resistance predominately in highly (80-95%) adherent individuals. In retrospect, HIV antiretroviral drug resistance during the first decade of effective therapy was not driven by poor adherence, but rather by the fact that early regimens were not po- tent enough to fully suppress the virus in patients who took most, if not all, of their medi- cations. The introduction of more potent ritonavir-boosted protease inhibitor and non-nu- cleoside reverse transcriptase inhibitor regimens have shifted this relationship towards full viral suppression and cessation of drug resistance at high levels of adherence. Similar concerns slowed the provision of HIV antiretroviral therapy in resource-limited set- tings based on the expectations that extreme poverty would lead to poor adherence and the global spread drug resistant virus. Data from most studies indicate that these concerns were overstated. Individuals in resource-limited settings consistently take >90% of their me- dication, compared to 70% in resource-rich settings. Furthermore, full viral suppression is possible in antiretroviral naïve patients on non-nucleoside reverse transcriptase inhibitors re- gimens, typical of resource-limited settings, at moderate levels of adherence. Rather, the risk of drug resistance in resource-limited settings appears to be more related interruptions in therapy due to structural and financial barriers to drug supply and distribution. These inter- ruptions in therapy lead to nevirapine monotherapy as nucleoside antiretroviral drug levels (stavudine and lamivudine) decay more rapidly than non-nucleoside reverse transcriptase in- hibitor drug levels (nevirapine) following a treatment interruption ( cthe nevirapine tail d). The sensitivity to treatment interruptions in resource-limited settings may be further accen- tuated by ethnic pharmacogenomic differences in drug metabolism, leading to more exten- ded periods of nevirapine monotherapy during an interruption. While efforts to sustain and prevent declines in adherence will be important in resource-limited settings, resistance will have less to do with forgotten doses, than ensuring a reliable drug supply and distribution system. 3Bangsberg DR, Moss AR, Deeks SG. Paradoxes of HIV antiretroviral adherence and drug resistance. JAC . 2004;53(5):696-699 . 12 SESSION 1 03. LABORATORY MONITORING OF HIV INFECTION AND EFFICACY OF ANTIRETROVIRAL TREATMENT E.M. Dax National Serology Reference Laboratory, Victoria, Victoria, Australia Nearly 95% of HIV infections have occurred in people living in resource limited settings. Since 2002, there has been a huge injection of funds into getting antiretroviral therapy to people in resource limited situations. This means a new era involving larger numbers of peo- ple on anti-retroviral treatments than ever before. To whom should therapy be given? How can the therapy get to those who need it; especially those in remote areas? How should its efficacy be assessed? How can the antiretroviral programmes 9 outcomes be gauged? How can opportunistic infections be diagnosed? Are diagnostic facilities and methods for CNS infections readily available? Part of the solution is in having effective laboratory systems. HIV testing and monitoring in developed countries is carried out in sophisticated laborato- ries employing commercially prepared test kits that are highly regulated by national systems, using highly developed testing strategies, expensive equipment and well researched testing methods, under strict quality management and with participation in quality assurance sche- mes. The rates of false results are extremely low. The variation in performances between la- boratories is low. However, these relative luxuries are not necessarily available in countries where regulation is absent. Purchase of kits may be by non-technical people with no under- standing of quality assurance and often through deals in which there is personal gain for the purchaser but none for the laboratories and therefore the patients. More recently, laboratories and funders have been paying greater attention to bringing re- liable testing and monitoring to resource limited areas. Testing strategies for diagnosis of in- fection employ simple rapid tests (even for screening blood donations). Thus, they have at- tained high levels of reliability. However, there may still be difficulties in the specificities of the combinations of the HIV tests used. Diagnosis of HIV infection may be better achieved but other laboratory tests may not. Many places do not have access to adequate microbio- logy laboratories or equipment such as that for conducting immunoassays or even adequa- te microscopes. There are more economic monitoring tools becoming available such as for viral load estimations using an assay that quantifies reverse transcriptase levels. Funders ha- ve started to recognize the importance of developing laboratory infrastructure for countries rather than setting up their own laboratories essentially for research purposes. Facilities and equipment for diagnosis of opportunistic infections often are not optimal but are receiving more attention as therapeutic programs are established. There are also new approaches to quality assurance that will provoke better training and performances from the laboratories as they develop. The NRL has developed a quality assurance method for monitoring the ability of test ope- rators to interpret tests 9 results. Tests have been shown to operate with high sensitivities and specificities. Other schemes for microbiology also employ photographed results for quality assurance purposes. 13 SESSION 1 04. PHARMACOECONOMICS AND ANTIRETROVIRAL THERAPY ROLLOUT IN BRAZIL A. Penalva de Oliveira Clinical Research Unit in Human Retrovirology, University of Campinas, San Paolo, Brazil The introduction of the Highly Active Antiretroviral Therapy (HAART), during the middle 1990 9s, brought with it a significant change on the course of the epidemic in developed countries. In the HAART context, the Brazilian situation is notable. Showing, at one hand, epidemic characteristics familiar to the majority of the underdeveloped nations, where mo- re than 90% of AIDS cases are present and the access to antiretroviral therapies is not avai- lable or limited and at the other hand, Brazil was the first developing country to have im- plemented a large-scale universal ARV distribution program. Brazil is a federal republic with approximately 172 million inhabitants, with a prevalence rate of HIV infection in 0,65% of the population. In 2005, about 170,000 HIV-infected patients receive antiretroviral drugs free of charge through the official Public Health System. A network of more than eight hun- dred public alternative care and HIV testing services has been established to provide the ne- cessary health structure to support this policy. The mortality rate and number of deaths from AIDS have fallen dramatically, particularly since 1996, with the free and universal distribu- tion of HAART. The average survival time before availability of combined therapy was less than 6 months and now is close to 5 years. This fantastic 12-fold increase is not only quan- titatively important: quality of life has also improved significantly. The occurrence of some common HIV-related opportunistic infections also has declined by 60 to 80%. Moreover, we have learned that waging war against HIV/AIDS is a good business. Millions spent in the short term can save billions in the long run. Since 1996 until now we have observed a se- ven-fold reduction in the hospitalization rates of HIV+ patients. This resulted in savings to the Government, together with the additional amount saved on ambulatory care, including drugs for opportunistic infections, rise to a more expressive total amount that were inve- sted in carrying out this policy. It should be noted, however, that such figures underestima- te the total net social benefit of providing treatment and care for people living with HIV/AIDS. Furthermore, the relative number of permanent public pensions requested in Bra- zil due to AIDS-related disabilities has fallen substantially since 1996. Focusing briefly on CNS complications, Toxoplasmic encephalitis (TE) experienced an expressive decline in abso- lute number of cases and relative incidence, but not too much expressive than other serial published data, representing significant cause of death and disabilities. It is important to mention that more than 1/3 of the patients did not know they had the HIV-infection, and in almost 3/4 of the total, the TE was the AIDS-defining illness. The data reflect, in rather brief and general terms, the delay in diagnosing the HIV-infection, and the loss of the op- portunity of using HAART. Finally, winning the fight against HIV/AIDS is not easy, cheap or quick. But our experience demonstrated that only with political will from Governments and full involvement of civil society and scientific academia we can defeat this pandemic. 14 SESSION 1 05. PHARMACOECONOMICS AND ANTIRETROVIRAL THERAPY ROLLOUT IN AFRICA C. Merry Trinity College, Dublin, Ireland Understanding the clinical pharmacology of antiretrovirals, antimalarials and antitubercular drugs is essential to the safe and effective roll-out of health care programs which aim to contribute to the achievement of the Millenium Development Goals. There are still limited data on the pharmacokinetics and pharmacogenomics of these drugs in populations which differ genetically, environmentally and behaviourally to their western counterparts in whom the initial dose finding and efficacy studies were carried out. In particular, there is a need to generate data on the optimal doses in children and pregnant women. Many of the drugs used in the management of diseases of poverty are substrates for and modulators of the cytochrome P450 system which leads to the potential for clinically significant drug- drug in- teractions. The key challenge for clinical pharmacologists is to generate these data and to interpret the results so that they may provide useful prescribing information for health ca- re providers who may have limited medical experience deep in the villages of the poorest countries of the world. 15 SESSION 2 06. GLOBAL EPIDEMIOLOGY OF HIV INFECTION AND AIDS G. Rezza Epidemiology Unit, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy The number of people living with HIV continues to grow, as does the number of deaths from AIDS. A total of 39.5 million (34.1 3 47.1 million) people were living with HIV in 2006, 2.6 million more than two years before. Moreover, an estimated 4.3 million adults and chil- dren were newly infected with HIV in 2006, which is about 400,000 more than in 2004. About two thirds of all adults and children with HIV globally live in Sub-Saharan Africa, with its epicentre in southern Africa. HIV epidemics dynamics are complex: declines in HIV pre- valence have been observed in some countries, following declines in HIV incidence rates. However, such trends are currently neither strong nor widespread enough to diminish the epidemics 9 overall impact. The introduction and widespread use of highly aggressive antire- troviral therapy has changed the face of the HIV epidemic in the industrialised world, whi- le in most developing countries access to appropriate treatment remains limited. All these factors determine differences in the overall impact of the HIV/AIDS epidemic between rich and resource-poor countries. Whether the different access to treatment, in addition to dif- ferences in the circulation of opportunistic agents, may influence the pattern of specific op- portunistic diseases, including CNS disease, remains undefined and influenced by possible diagnostic bias. 17 SESSION 2 07. EPIDEMIOLOGY OF HIV CNS DISEASE IN SUB-SAHARAN AFRICA J. Hakim Dept. of Medicine, University of Zimbabwe, Harare, Zimbawe Of the more than 40 million people living with HIV/AIDS, the majority live in resource-limi- ted settings. Central nervous system disorders are a significantly cause of morbidity and mortality among these HIV infected individuals. The causes and manifestations of HIV asso- ciated central nervous system disease in resource-limited settings have been poorly descri- bed because of limitations in the availability of diagnostic procedures such as neuro-ima- ging, microbiological, serological and other sophisticated diagnostic techniques. Meningitis, stroke and mass lesions of the spine and brain have all been described in asso- ciation with HIV infection. In Zimbabwe cryptococcal, meningitis has become the commo- nest cause of meningitis with 45% of 200 cases being due to cryptococcal meningitis in a series of cases of pyogenic, tuberculous, and mononuclear meningitis seen at a tertiary ho- spital level. In a Malawian study of 98 patients presenting with stroke, 92 had CT scans of the brain. Of the 43 HIV sero-positive patients, 9 (21%) had an infective condition leading to presentation with stroke compared to none among the 49 HIV sero-negative patients. In India and Brazil toxoplasmosis is an important cause of brain mass lesions in HIV infected individuals. Indeed, inspite of the early and widespread introduction of HAART in Brazil to- xoplasmosis continues to be an important condition especially in those with low CD4 counts. The distribution of causes of CNS disease in HIV infected patients in developing countries is a reflection of the prevalence of HIV infection in a given geographical locality, the type of endemic diseases in that region and the impact of the use of prophylactic and antiretrovi- ral drugs. The reported contribution of various conditions in resource-limited countries is heavily influence by the diagnostic capabilities in these settings. 18 SESSION 2 08. EPIDEMIOLOGY OF HIV CNS DISEASE IN BRAZIL AND SOUTH AMERICA J.E. Vidal Instituto de Infectologia "Emilio Ribas", San Paolo, Brazil Highly active antiretroviral therapy (HAART) has improved the prognosis of several neurolo- gical complications of human immunodeficiency virus (HIV) infection in developed coun- tries. However, these diseases continue to cause important morbidity and mortality in deve- loping countries. Opportunistic infections of the central nervous system (CNS) represent a main cause of hospital admission in several places of South America, including some set- tings where HAART is available. However, there are few epidemiologic studies and publica- tions about this problem. When brain expansive lesion syndrome predominates, the main diagnosis include toxoplasmosis, focal forms of tuberculosis (tuberculomas and/or abscess), and rarely CNS primary lymphoma. When meningeal or meningoencephalitis syndrome pre- dominates, the main diagnosis are cryptococcosis, tuberculosis, and syphilis. For these rea- sons, CNS tuberculosis is an important neurological complication in South America. In con- trast to previous clinical and anatomopathological reports, which progressive multifocal leu- koencephalopathy (PML) always was rarely reported, in recent years we observed several ca- ses of PML laboratory-confirmed with detection of JCV DNA in cerebrospinal fluid. In addi- tion, although there is no data about the prevalence of HIV-related neurocoginitive disor- ders, the number of patients with this problem is relatively frequent in clinical practice. In contrast of their important benefits, the growing use of HAART in South America introdu- ces some important issues, including: (1) immune reconstitution inflammatory syndromes, specially in cases of tuberculosis, cryptococcosis, and PML, and (2) toxic effects of antiretro- virals, specially peripheral neuropathy and HIV-associated neuromuscular weakness syndro- me. This broad clinical spectrum of central and peripheral neurological manifestations is complicated due to the presence of endemic infections in South America, for example Cha- gas disease and histoplasmosis causing meningoencephalitis and focal brain lesions, and le- prosy causing peripheral neuropathy. In summary, this context highlights urgent need to perform neuroepidemiologic studies to better understand the current situation of primary and secondary HIV-associated neurological complications in South America. 19 SESSION 2 09. EPIDEMIOLOGY OF HIV CNS DISEASE IN INDIA M. Ghate National AIDS Research Institute, Pune, India The estimated number of HIV infections in India increased from a few thousands in the ear- ly 1990s to over 5 million in 2005. The main mode of HIV transmission is heterosexual and HIV-1 subtype C is the most common form of the virus in India. The standard medical care for HIV/AIDS in India mainly consists of symptomatic treatment, chemoprophylaxis and ma- nagement of opportunistic infections. Government of India has initiated free ART roll out programme since 2004 and currently around 53,000 patients are on ART. With the transi- tion of epidemic from HIV to AIDS, clinical neurologic manifestations have been increasin- gly observed. This presentation reviews published data from Indian literature on neurologi- cal findings. In late 90s, an autopsy study from western India reported CNS lesions in 79% cases of which 38% were opportunistic infections. In cross sectional studies from southern as well as western parts of India, the commonest reported neurological opportunistic infec- tions were neurotuberculosis, cryptococcosis and toxoplasmosis. A study on hospitalized patients from a southern state reported an overall prevalence of neurological findings in 26.6% patients. Of these, meningitis was reported in 39.4% and tubercular meningitis was more common than cryptococcal meningitis (25.05% vs. 10.95%). Non opportunistic neu- rological manifestations reported in 67 out of 300 patients (22.3%) from western India in- cluded stroke syndromes (29.8%), demyelinating illnesses (5.9%) and AIDS dementia com- plex (5.9%). The other manifestations mainly included HIV neuropathy (38%). As compa- red to the neurological studies carried out in developed countries there are lacunae in so- me of the studies such as establishment of definitive diagnoses by uniform definitions, lack of data on certain neurological investigations and their correlation with immunological and virological parameters due to economical constraints in resource limited setting. Majority of the data are on the ART naïve population and with the introduction of free ART roll out pro- gramme by the Indian Government, it is important to undertake more studies which focus on the neurological findings in the post HAART era. References : 1. Dhaneshwar N. Lanjewar, Paresh P. Jain and Chandrasekhar R. Shetty. Profile of central nervous sy- stem pathology in patients with AIDS: an autopsy study from India. AIDS 1998, 12:309 3313. 2. Vijay D. Teja, MD; Sudha Rani Talasila, MSc; Lakshmi Vemu, MD. Neurologic manifestations of HIV Infection: An Indian Hospital-Based Study. AIDS Read. 2005; 15 (3): 139-145. 3. Nonopportunistic Neurologic Manifestations of the Human Immunodeficiency Virus: An Indian Stu- dy. Medscape General Medicine. 2005; 7(4):2. 20 SESSION 2 10. ANTIRETROVIRAL THERAPY ROLLOUT IN CHINA F.J. Zhang Division of Treatment and Care at China National Center for AIDS/STD Prevention and Control, Beijing, China In 2002, the need for an emergency response to the growing numbers of AIDS patients li- ving mainly in impoverished regions of central China without access to care led to the ini- tiation of China 9s Free ART Program. Limited resources and little experience with HIV/AIDS treatment and care have at times frustrated China 9s efforts to provide free antiretroviral the- rapy on a wide scale, but from its origin as an emergency response, the Free ART Program is developing into a standardized system of comprehensive treatment and care with the aim and capability to save and improve the lives of large numbers of AIDS patients who could otherwise not afford treatment. National guidelines, training programs, a national patient database, supplementary programs for special populations such as children and co-infected patients, and operational research have all added to the scope and quality of the program. Anti-retroviral therapy was first piloted in China in December of 2002 among a small group of 100 patients. In December 2003, the Chinese government announced its cFour Frees One Care d guaranteeing free ART Treatment to all rural AIDS patients and urban patients with financial difficulties. Since 2003, treatment has been scaled up from the initial 8 pro- vinces to all 31 of China 9s provinces. As of December 30, 2006, 30,197 patients in 31 pro- vinces, autonomous regions, and special municipalities had received free ART treatment. The nature of China 9s healthcare system and the demographics of the patient population present a unique set of challenges to the progress of the program, but with continued sup- port from the government as well as a diverse set of resources, China has every ability over- come such obstacles and successfully provide reliable access to high-quality care nation-wi- de. 21 SESSION 3 11. HIV DEMENTIA AND COGNITIVE IMPAIRMENT IN RESOURCE-LIMITED SETTINGS N. Sacktor Johns Hopkins University Department of Neurology, Baltimore, Maryland, USA HIV associated cognitive impairment and HIV dementia remain as important neurological manifestations of advanced HIV infection in the era of highly active antiretroviral therapy (HAART). HIV dementia has a major impact on quality of life, and is predictive of poor sur- vival in patients with HIV infection. The prevalence of HIV dementia in international settings with the highest HIV seroprevalence rates is largely unknown. In this presentation, clinical issues related to the diagnosis of HIV-associated cognitive impairment in resource-limited settings will be summarized. The use of a screening tool, the International HIV Dementia Scale (IHDS), to identify potential HIV+ individuals at risk for HIV dementia in an internatio- nal setting will be described. Data examining the frequency of HIV dementia in internatio- nal settings will be reviewed. In Uganda, recent data suggest that HIV dementia may affect 30% of HIV+ individuals with advanced infection who have not received antiretroviral the- rapy. If a similar proportion exists in the HIV+ population in other countries in Africa and in Asia, then HIV dementia may be an under-diagnosed condition, which warrants further eva- luation in an outpatient clinic setting. 23 SESSION 3 12. CENTRAL NERVOUS SYSTEM TUBERCULOSIS G.E. Thwaites Wellcome Trust Clinical Research Fellow, Department of Infectious Diseases, Imperial College, London, UK Okford University, Ho Chi Min City, Vietnam Tuberculosis can affect the central nervous system in two ways: tuberculous meningitis (TBM), or space-occupying lesions known as tuberculomas. Both can affect the brain or spi- nal cord and are more common in those with HIV infection; both present enormous chal- lenges to physicians worldwide. I will examine the published data concerning the diagnosis and treatment of central nervous system in HIV infected individuals and highlight the cur- rent areas of uncertainty in clinical management. 24 SESSION 3 13. HIV, THE CENTRAL NERVOUS SYSTEM AND STROKE J. Heikinheimo-Connel Terttu University of Malawi, College of Medicine, Medicine Department, Blantyre, Malawi Since late 1990 9s scientists have debated whether HIV is an independent risk factor for stro- ke. In HIV burdened countries the prevalence of strokes has increased amongst the youn- ger age groups (under 40 years old). The possible mechanisms of stroke amongst the HIV positive patients are opportunistic infections, prothrombotic states, non-bacterial endocar- ditis, aneurismal vasculopathy protein S deficiency or HAART- medication. Infections are al- so an important differential diagnosis for stroke-like symptoms in resource-limited settings like Malawi. 25 SESSION 3 14. HIV AND MICROBIAL COINFECTIONS IN THE CENTRAL NERVOUS SYSTEM S. de Almeida Virology Laboratory, Hospital de Clinicas, Federal University of Paraná, Curitiba PR, Brazil The pandemic of HIV/AIDS continues to grow daily. Incident cases among women, intrave- nous drug users and ethnic minorities comprise the fastest growing segment of the HIV-in- fected population, and the number of HIV-infected individuals over the age of 50 is gro- wing rapidly. Today, the central nervous system and the immune system are seen as main targets of HIV infection. Significant progress in the knowledge and treatment of AIDS has been obtained in recent years, leading to a significant improvement on life expectancy. In Brazil there are some endemic diseases with importance for nervous system. Some of the- se endemic diseases of virus origin are dengue fever, HTLV 1 and 2; of bacterial origin are tuberculosis and leprosy; parasitic diseases as cysticercosis, malaria falciparum and vivax, schistossomiase and Chagas disease and fungus diseases as infections caused by Paracoc- cidiodis brasiliensis. All these diseases are very common in some geographical areas, as is the HIV infection, so it is expected that co-infection occurs. Although the association with HIV could not increase the incidence of these infectious diseases in a significant proportion. The co-infections can alter the clinical, laboratorial, immunology and response to treatment of both HIV and the disease associated. However, there are very few studies about CNS en- demic diseases and HIV co-infection in Brazil, concerning clinical and laboratorial characte- ristics, cerebrospinal fluid (CSF) characteristics and prognoses. Trypanossoma cruzy is endemic in most South and Central American countries, it is the etio- logical agent of Chagas disease. Patients with Chagas disease and HIV co-infection may pre- sent unusual clinical manifestations such as skin lesions, involvement of CNS, and or serious cardiac lesions related to the reactivation. In the HIV-infected host, Chagas disease most of- ten reactivates in the CNS, usually when the patient 9s CD4+ cell count is <200 cells/mm3 but the disease has been reported in a patient with higher CD4+ count. Meningoencephalitis is the most common CNS manifestation of chronic infection in immu- nocompetent hosts but usually occurs only in children. CNS mass lesions have not been re- ported in immunocompetent hosts. In the immunosuppressed host, CNS manifestations oc- cur more frequently and can include meningoencephalitis or a brain mass. Diagnosis is con- firmed by direct observation of intracellular trypomastigotes in serum or CSF. Serum antibo- dies detection tests are sensitive and specific for both acute and chronic forms of T cruzi in- fection. Neuroimages of the brain typically show > 1 ring-enhancing lesions involving both gray and white matter. Acute communitarian bacterial meningitis and AIDS are diseases of compulsory notifications in Brazil. This is an example of how the HIV co-infection alter the clinical characteristics and prognostic of an associated disease. The mortality rate was 56%, higher than the overall meningitis mortality rate of this period. All cases with meningitis by S. pneumoniae died. CSF basic characteristics may be different from those found in bacterial meningitis in not HIV infected patients, the number of white blood cells (WBC) in the group without HIV co- infection was higher than in the group with HIV co-infection (p 0.12), glucose was lower (p 0.04), and the percentage of neutrophils was higher (p 0.008) in the group without HIV co- infection. S. pneumoniae was the more frequent etiologic agent. There was higher rate of unidentifiable bacteria in CSF. HIV+ individuals are more likely to develop acute bacterial meningitis from less common bacteria for the age group. There has been a dramatic increase in the number of cases of syphilis during the era of AIDS. Evidence of an increased occurrence of syphilis with HIV infection has been previou- 26 sly reported. The association would be expected because HIV and syphilis are both sexually transmitted diseases. Syphilis is an example of how the co-infection with HIV can alter the syphilis and the HIV clinical characteristics. Syphilis and HIV co infection increases HIV tran- smission; clinical syphilis characteristics are not typical; there is more frequency of asympto- matic primary syphilis and higher frequency of secondary syphilis; secondary syphilis is mo- re aggressive; higher neurological and ophthalmologic involvement; higher number of fal- se negative serologic results and greater recidive of the infection. Invasion of the central ner- vous system by the Treponema pallidum can occur at any stage of the syphilitic infection, and occurs in about 10 to 55% of untreated patients. Neurosyphilis has been reported to develop in one third of patients who progress to late stages of the disease. Neurosyphilis is more frequent in HIV patients (23%) than in non HIV patients (10-17%). Co-infection with syphilis increases blood HIV viral load, the same way neurosyphilis may amplify intrathecal HIV replication, possibly through immune activation. It is known that elevated CSF RNA le- vels correlate with cognitive impairment, neurosyphilis may cause increased CNS manifesta- tions of HIV. The co-infection of endemic diseases and HIV can alter the characteristics of both diseases, although the majority of these co infections need more accurate studies. 27 OPEN PRESENTATIONS 15. CEREBRAL TOXOPLASMOSIS IN JAKARTA D. Imran 12 , H. Khosama 12 , J. Jannis 12 1 Department of Neurology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia 2 Cipto Mangunkusumo Hospital, Jakarta, Indonesia Cerebral toxoplasmosis was the most common cause of focal brain lesions in HIV patients in Jakarta. We conducted a retrospective study by reviewing medical charts of 88 presumtive cases of cerebral toxoplasmosis at Cipto Mangunkusumo hospital in Jakarta from January 2004 un- til March 2006. All of these patients showed neurological signs and symptoms, and focal brain lesion(s) on neuroimaging studies and received anti-toxoplasmic treatment. 'The majority of the patients were male (87%). The age of the patients ranged from 19 to 48 years with a mean of 27 years. Intravenous drug user 9s 81%. Focal brain lesion(s) was the reason for detection of HIV infection in 82% of these patients. CD4 cell count ranged from zero to 172 cell/µL with a mean of 37 cell/µL. Toxoplasma serology was perform on 54 patients and all of them were seropositive. Forty-one (47%) of the patients presented with abnormal mental status, almost all of the patients (83%) with headache. Fever was present in 43%, focal neurological signs and symptoms showed in 50%, and seizure was found in 33%. Multiple lesions on brain CT scan were seen in 70 (79%). Sixty-three (72%) of the patients who received anti-toxoplasmic treatment showed clinical improvement and 45 of them (73%) had improvement by day 7. Response to treatment ranged from day 2 to day 30. Patients with pulmonary tuberculosis tended to have poor response. Response to anti-toxo- plasmic treatment was significantly associated with level of consciousness on admission and contrast enhancement on focal brain lesion(s). 29 OPEN PRESENTATIONS 16. ASSOCIATED FACTORS TO IN-HOSPITAL MORTALITY AND LONG-TERM SURVIVAL IN BRAZILIAN HIV-INFECTED PATIENTS WITH TUBERCULOUS MENINGITIS IN THE HAART ERA M.G. Croda 1 , J.E. Vidal 1,2 , A.C. Penalva de Oliveira 1,3 1 Emilio Ribas Institute of Infectious Diseases, San Paolo, Brazil 2 University of San Paolo, San Paolo, Brazil 3 University of Campinas, San Paolo, Brazil Tuberculous meningitis (TM) is a major cause of death and disability in HIV-infected patients in developing countries. The objective of this study was to identify associated factors to in- hospital mortality and long-term survival in Brazilian co-infected patients in the highly acti- ve antiretroviral therapy (HAART)-era. This retrospective study included 86 HIV-infected patients admitted at the Emilio Ribas In- stitute of Infectious Diseases in Sao Paulo, Brazil, who had M.tuberculosis isolated from ce- rebrospinal fluid during 2000-2006. Patients with other neurological diseases were exclu- ded. Clinical and laboratorial data were collected. The severity of TM at admission was clas- sified using the British Medical Research Council (BMRC) criteria. Multivariate analysis by lo- gistic regression was used to identify associated factors to in-hospital mortality. Cox-propor- tional hazard model was constructed for long-term survival (9 months). The median of age was 35 years (6-56), and 75% were male. TM was AIDS-defining illness in 48 (56%) cases. Forty-eight (56%) patients had previous diagnosis of tuberculosis. The classification of the BMRC revealed 40%, 35%, and 25% of the patients with grades I, II, and III, respectively. Extraneural tuberculosis was diagnosed in 35 (41%) patients. The me- dian of CD4 T-cell count was 64 cell/µl. Thirty-seven (46%) patients reported use of antire- troviral at admission. The global mortality was 54% (30% in-hospital and 24% in long term). In univariate analysis, extraneural tuberculosis, BMRC grade III at admission, CSF to- tal WBC <200, CD4 T cell count <50 cells/µl, albumin g/dl< 3, headache at admission and no use of corticosteroids were associated with in-hospital mortality. In multivariate analysis, only BMRC grade III at admission (OR=6.7; 95%IC=2.3-19.3; P=0.02) and extraneural tu- berculosis (OR=3.8; 95%IC=1.2-12.8; P=0.0004) remained associated with in-hospital mor- tality. At the 9 months of follow-up, BMRC grade III at admission (HR=4.8; 95%CI=1.1- 4.85; P=0.01), extraneural tuberculosis (HR=3; 95%CI=1.4-6.4; P=0.0005) and CD4 T cell count <50 cells/µl (HR=3.8; 95%CI=1-4.5; P=0.04) were predictors associated with morta- lity. TM cause high mortality in the HAART-era in Brazil. The severity of neurological involvement and disseminated tuberculosis were associated to in-hospital mortality. These variables and severe immunosupression were associated with long-term mortality. 30 OPEN PRESENTATIONS 17. COINFECTION WITH HUMAN T-CELL LYMPHOTROPIC VIRUS AND HUMAN IMMUNODEFICIENCY VIRUS: PRELIMINARY RESULTS OF A BIG COHORT FROM RIO DE JANEIRO, BRAZIL M.T.T. Silva, M.J. Andrada-Serpa, E.B. Braga, D.P. Campos, H. Hojas, B. Grinsztejn, R.C. Harab, M.S. Oliveira, A.C.C. Leite, M.A. Lima, A. Araújo Evandro Chagas Clinical Research Institute - FIOCRUZ, Rio de Janeiro, Brazil HTLV and HIV share a common tropism for T cells and have the potential to affect nervous system. 5% of HTLV-1-individuals will develop HTLV-1-myelopathy (HAM). Furthermore, other diseases, especially peripheral neuropathy (PN), have been associated with HTLV-1. In the other hand, neurological disorders have been reported as very frequent in AIDS patients. There is a reasonable concern about increased risk to neurological diseases in HIV/HTLV- coinfected individuals. In the other hand, conflicting reports suggest variable outcomes in HIV disease among dually infected individuals, including delayed progression to AIDS and accelerated disease progression. We aim to present our preliminary results of a clinical and epidemiological study on HIV/HTLV coinfection. From a cohort of 713 HTLV individuals we randomly selected 90 with negative HIV serolo- gy (G1). From a cohort of 4624 HIV individuals, we randomly selected 486 to HTLV-antibo- dies determination (G2 3 HIV single infection; G3 3 HIV/HTLV coinfection). All patients we- re submitted to a full neurological assessment, HIV viral load, HTLV proviral load, and CD4/CD8 count. Occurrence of opportunistic infections (OI) and deaths since the entry in one of these cohorts was registered. 51/486 HIV individuals were coinfected with HTLV. PN and/or HAM was slightly more com- mon in G3 (46/51; 90%) than in G1 (79/90; 87.7%). In the other hand, these diseases we- re more common in G3 than in G2 (42/435; 9.6%) [X 2 54.8; p < 0.0001]. Death was mo- re common in G3 (12/51) than in G2 (24/435) [X 2 28.9; p < 0.0001]. There is no differen- ce in OI prevalence among G3 and G2 (26/51 vs 224/435; X 2 0.05). There is no differen- ce in CD4/CD8 counts or HIV viral load among G2 (median 411/862) and G3 434/889). Al- so, there is no difference in HTLV proviral load among G1 (9.4 HTLV copies per 100 PBMCs) and G3 (6.5 copies). In our preliminary results, HIV/HTLV coinfection was not associated with a higher risk to NP or HAM comparing with HTLV single infection. As expected, these diseases were more com- mon in HIV/HTLV than in HIV single infection. We will perform a full neuropsychological eva- luation in the future. 31 OPEN PRESENTATIONS 18. PRESENCE OF TROPICAL SPASTIC PARAPARESIS/HTLV-ASSOCIATED MYELOPATHY (TSP/HAM) DIAGNOSIS AMONG HIV-1/HTLV-II-COINFECTED SUBJECTS IN SÃO PAULO CITY P. Montanheiro 1 , I. Olah 1 , L.M.I. Fukumori 1 , M.P. Vergara 2 , J. Smid 2 , A.C. Penalva de Oliveira 2 , A.J.S. Duarte 1 , J. Casseb 1,2 1 Laboratory of Dermatology and Immunology, Medical School São Paulo University, San Paolo, Brazil 2 HTLV Out Clinic, Institute of Infectious Diseases cEmilio Ribas d, San Paolo, Brazil Background : HTLV-II infection is usually a silent infection, but some neurological symptoms have been described and few data regarding proviral load have been published. Methods : We studied 64 HTLV-II-infected subjects (37 men and 27 women, mean of 40 ye- ars of age) who have following up in our clinic in the last nine years. HTLV-II DNA proviral load (PVL) was measured by real time PCR, with a cut off 10 copies per 10.000 PBMCs. Two of 41 HTLV-II/HIV-1 (5%) cases had a TSP/HAM-like diagnosis, but none in solely HTLV- II-infected individuals. We noted there was a gender difference regarding PVL. Only two of 27 women had detectable PVL (20 copies/104 PBMCs), whereas 16 of 37 men had detec- table PVL (p=0,005), and it was more likely to occur among those older than 40 years of age. 1) Higher prevalence of TSP/HAM simile diagnosis among co-infected HTLV-II/HIV-1 subjects compared to those solely HTLV-II-infected subjects. 2) There was gender difference might be the mode of transmission. Men were more likely IDUs, and women were usually infected during sexual intercourse with IDU partners. 32 OPEN PRESENTATIONS 19. IMPACT OF ACCESS TO CARE ON THE NEURODEVELOPMENT OF HIV-INFECTED CHILDREN IN A RESOURCE POOR AFRICAN SETTING A. Van Rie 1 , A. Mupuala 2 , A. Dow 1 , N. Kilese 3 , I. Zephyrin 4 , N. Nossa 3 1 Department of Epidemiology, the University of North Carolina, Chapel Hill, North Carolina, USA 2 Department of Pediatrics, the University of Kinshasa, Kinshasa, Democratic Republic of Congo 3 The University of North Carolina at Kinshasa, Kinshasa, Democratic Republic of Congo 4 Department of Physiotherapy, University of Kinshasa, Kinshasa, Democratic Republic of Congo With the introduction of HAART in the US, perinatal HIV has almost been eradicated, and the prevalence of HIV encephalopathy has dropped dramatically from more than 30% pre- HAART to an estimated 1.6 %. As of 2006, over two million children are living with HIV in- fection globally, but few have access to care and even less have access to HAART. Little is known about the impact of HIV care on the neurodevelopment of HIV-infected children. Neurodevelopment was assessed longitudinally over a 1 year period in three groups of chil- dren age 18 to 71 months. We enrolled 35 HIV-infected children, 35 HIV-affected children (AIDS orphans or children living with parents suffering from AIDS), and 90 HIV-unexposed healthy children. All children resided in Kinshasa, Democratic Republic of Congo. Depen- ding on the age of the child, the Bayley, Peabody, and/or SON-R 2_-7 instrument was used to assess motor and mental development. Among those children with data available for all 3 visits, the prevalence of severe neurode- velopmental impairment (motor or mental) in HIV-infected children (n=26) was 50% at ba- seline, 41% at 6 month follow up and 20% at 12 month follow up. Neurodevelopmental delay was more frequently observed among children eligible for ART compared to those children not eligible for ART. The prevalence of severe mental impairment decreased from 50% at baseline to 27% at the 12 month visit, prevalence of severe motor impairment de- creased from 12% at baseline to 4% at 12 month follow up. Motor development did not improve between baseline and 12 month follow up visit in HIV affected and control chil- dren. In contrast, improvement of mental development was also observed among HIV af- fected (n=29) or control children (n=40), probably due to a learning effect of using the sa- me instruments multiple times among children that otherwise have with few educational opportunities. The neurodevelopment of HIV infected children appeared to improve in the first year of en- try in an HIV care program. While improvement of motor development was only observed in HIV-infected children, improvement of mental development was observed in all 3 groups, probably indicating a learning effect. 33 POSTERS P01. LIMITATIONS OF DIAGNOSIS OF CNS INFECTIONS IN HIV CASES IN FIJI ISLANDS K. Kishore 1 , S.T. Ali 2 1 Fiji School of Medicine, Fiji 2 Reproductive Health Clinic Fiji Ministry of Health, Fiji This report depicts constrains of diagnosing CNS infections in a resource limited setting such as Fiji, especially after availability of ARV through GF-ATM about three years ago. Data from the Reproductive Health (RH) Clinic in Suva have been collated to analyze the current state of facilities and usage for diagnosis of CNS infections. Since getting first HIV positive case in the country in 1989, Fiji now has more than 230 laboratory- confirmed ca- ses. The exact total number of surviving cases is difficult to estimate due to lack of follow up in the past. Among the persons on regular follow up, RH clinic currently has 45 or about 90 % of the total HIV cases in the country under its care. Among them, 36 of these cases are from Fijian race, 4 Indians, and 5 represent the other races. RH also houses the HIV chub d for distribution and follow-up of Anti-retroviral drugs in the country. At present 29 HIV positive persons are on ARV through this hub. Since commencing HIV care, RHI clinic in Suva has investigated 4 cases for suspected CNS infection through lumbar puncture. Of these 2 were suspected of Toxoplasma infection, and 2 of Cryptococcal infection. The only positive case for Crypto since has died. In addition, 10 cases were investigated for CNS manifestations of HIV related dementia & depression as part of APNAC study 2 years ago. Number of people living with HIV AIDS in Fiji is steadily rising. This trend would go upward as more people commence ARV. Due to this, opportunistic infections would also rise, the- reby increasing need for facilities for their diagnosis. Despite reasonably high number of HIV cases under care, investigations for CNS infections have remained very low. Multiple factors contribute to this, mainly, lack of expertise due to staff shortage & rapid turn over due to migration etc, & high work load at the clinic. Importantly, lack of facilities & expertise in the lab for proper diagnosis, and unavailability of medications for treatment and follow up at the clinic has created a culture whereby health care staffs remain reluctant to conclusively investigate a case of CNS infection. This results in management of CNS infections sympto- matically. 34 POSTERS P02. HIV POSITIVE PATIENTS FROM THE ASIA PACIFIC REGION WHO RECEIVE NEUROHAART ARE LESS LIKELY TO HAVE HIV-RELATED NEUROCOGNITIVE IMPAIRMENT: FINDINGS OF THE ASIA PACIFIC NEUROAIDS CONSORTIUM (APNAC) STUDY L. Lal 1,2 , E. Wright 1,2,3 , B. Brew 4,5 , A. Arayawithchanont 6 , K. Robertson 7 , K. Samintarapunya 8 , S. Kongsaengdao 9 , M. Lim 2 , S. Vonthanak 10 , L. Lal 2,3 , C. Sarim 10 , S. Huffam 10,11 , P. Li 12 , D. Imran 13 , J. Lewis 2 , W.H. Lun 14 , A. Kamarulzaman 15 , G. Tau 16 , S. Ty Ali 17 , K. Kishore 18 , M. Bain 4 , R. Dwyer 3 , G. McCormack 2 , M. Hellard 1,2,3 , C. Cherry 1,2,3 , J. McArthur 19 , S. Wesselingh 1,2,3 1 Burnet Institute, Melbourne, Australia 2 Monash University, Melbourne, Australia 3 The Alfred Hospital, Melbourne, Australia 4 St Vincent's Hospital, Sydney, Australia 5 University New South Wales, Sydney, Australia 6 Sappasithiprasong Hospital, Ubon Ratchathani, Thailand 7 North Carolina of Chapel Hill, Chapel Hill, North Carolina, USA 8 Lampang Hospital, Lampang, Thailand 9 Rajavithi Hospital, Bangkok, Thailand 10 National Centre HIV/AIDS, Dermatology and STD, Phnom Penh, Cambodia 11 National Centre HIV Epidemiology and Clinical Research, Sydney, Australia 12 Queen Elizabeth Hospital, Hong Kong, China 13 Cipto Mangunkusomo Hospital, Jakarta, Indonesia 14 Ditan Hospital, Beijing, China 15 University of Malaya Medical Centre, Kuala Lumpur, Malaysia 16 Port Moresby General Hospital, Port Moresby, Papua New Guinea 17 Reproductive Health Clinic, Fiji Ministry of Health, Suva, Fiji 18 Fiji School Medicine, Suva, Fiji 19 Johns Hopkins School Medicine, Baltimore, Maryland, USA Background : There are 8.3 million HIV positive people living in the Asia Pacific (AP) region of whom 14% receive highly active antiretroviral therapy (HAART). The prevalence of HIV- related neurocognitive impairment (NCI) within this region is not known. The benefit of neuroHAART -antiretroviral regimens containing three or more agents known to penetrate cerebrospinal fluid in effective concentrations-in preventing or improving HIV-related NCI has been subject to debate. We hypothesized that the use of neuroHAART in patients en- rolled into the APNAC study would confer a neurocognitive protective benefit. Methods Between July and March 2006, we undertook a cross-sectional study at 10 sentinel sites wi- thin China, Thailand, Cambodia, Malaysia, Hong Kong, Indonesia, Papua New Guinea and Fiji to determine the prevalence of moderate 3severe HIV-related neurocognitive impairment and symptomatic sensory neuropathy. We reviewed case records for clinical and antiretro- viral treatment histories and investigation results. NeuroHAART was defined as above and neuroactive agents were defined as nevirapine, efavirenz, stavudine, lamivudine, abacavir, zidovudine and indinavir. We administered a sensitive four-test neuropsychological battery to 658 HIV positive patients. A patient was defined as having moderate to severe HIV-rela- ted NCI if they had e -2SDs below local controls 9 mean scores in two of the four neuropsy- chological tests. Univariate and logistic regression analyses were applied to the data. Results 76 patients (11.7%) (95% confidence interval [CI] 9.3 314.2) were neurocognitively impai- red. Several potential confounders including depression and prior CNS AIDS illness were not significantly associated with neurocognitive impairment (OR 1.49

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