Abstract Book Vol. 2 [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

XIV International AIDS Conference Abstracts ThPeB7278-ThPeB7281 405 in advanced stages of various opportunistic infections, often severely ill with CD4 < 200. TB leads all the other infections. JCRC has a fully operational outpatients clinic, an inpatient facility and a well-equipped laboratory to carryout research and diagnostic work. Method: A retrospective review of all inpatients' files was carried out from 2nd January to 31st December 2001. 4000 patients were seen at the outpatients' clinic. Out of 4000 patients, 254 were new admissions and 25% readmissions. Results: 95% of the 254 admissions were seropositive and 15% were receiving ARV therapy. Majority of the patients had TB (25.2%). Other opportunistic infections included cryptococcal meningitis (9.4%), toxoplasmosis (13.4%), Candidiasis (14.2%), Gastroenteritis (11.%) and PCP (13.4%). The most common was atypical with disseminated disease and sputum smear negative (50%), Extrapulmonary (2%), Primary (10%) and (2%) relapse Conclusion: TB is the leading cause of HIV related diseases we see at the JCRC OPD clinic and the ward. The combination of ARV and TB therapy increases the number of pills a patient has to take and may lead to noncompliance thus causing drug resistance to TB and HIV JCRC has adopted the DOT approach as a way of ensuring that drugs are taken as prescribed. Relatives are instructed to follow the DOT method. Presenting author: Mary Nasira Mulindwa, Joint Clinical Research Centre, Butikiro House, Mengo, P. 0. Box 10005, Kampala, Uganda, Tel.: +256 041 270283, Fax: +256 041 342632, E-mail: [email protected] ThPeB7278 Cellular source and increased HIV-1 replication and heterogeneity at sites of tuberculosis Z.T. Toossi1, E.J.A. Arts2, S.L. Lawn2, C.K. Collins2. 1Case Western Reserve University, 10900 Euclid Ave, CWRU, Infectious diseases, Cleveland ohio,; 2case western reserve university, ohio, United States Background: Tuberculosis (TB) enhances HIV-1 activity and ultimately the progression to AIDS in dually infected subjects. We employed pleural TB as a model to understand the interaction of the host with HIV-1 during active TB, at sites of MTB infection. Patients were recruited in Kampala, Uganda. Methods: Blood and pleiral fluid (PLF) were obtained after informed consent. Patients had CD4 cell counts of 34-705 cells/Vl and plasma and PLF viral loads of 2,400-280,000 and 7,600-4,500,000 copies/ml, respectively. Results: HIV-1 replication was enhanced both in the cellular, and acellular compartments of the pleural space as compared to blood. Several potential mechanisms for expansion of HIV-1 in situ were found including: augmentation in expression of TNF-a and the HIV-1 non-inhibitory b-chemokine (MCP-1), low presence of HIV-1 inhibitory b-chemokines, and up-regulation of the HIV-1 co-receptor, CCR5. Next, the C2-C3 region of env was PCR amplified from PBMC and PLF cells, and by reverse transcriptase-PCR amplified from plasma and PLF. A compartmentalization of HIV-1 quasispecies in 4 of 8 patients, with migration events between the two compartments was seen. A trend for a greater genetic heterogeneity in the pleural space was found. Paired plasma and pleural fluid samples were analyzed by immunomagnetic capture of host proteins incorporated into the HIV-1 envelope. A 4.0-fold greater median HIV-1 load in pleural fluid compared to plasma (P <.01) was derived from viral replication within HLA-DR+ cells, CD26+ lymphocytes, and importantly CD14+ macrophages. Conclusions: Thus, HIV-1 replication and heterogeneity were increased at sites of MTB coinfection, and the mononuclear cells activated lymphocytes and macrophages supported HIV-1 replication. Transcriptional activation of HIV-1 in latently infected mononuclear cells, and facilitation of viral infection of newly recruited cells were implicated, which may contribute to enhanced viral burden and dissemination during TB. Presenting author: Zahra Toossi, 10900 Euclid Ave, CWRU, Infectious diseases, Cleveland ohio, United States, Tel.: +1 216 368 4844, Fax: +1 216 368 2034, Email: [email protected] ThPeB7279 Epidemiological profile of patients with tuberculosis in Durban Q.A.K. Abdool- Karim. Fogarty AITRP Congella, Durban, South Africa Background: Tuberculosis (TB) is the leading cause of morbidity and mortality in South Africa. Co-infection with HIV is a major contributor to the growing burden of tuberculosis placing greater imperatives for enhancing tuberculosis case management. The National TB Control Programme implemented the directly observed treatment short course (DOTS) strategy in 1996, but its implementation varies across South Africa. Aim: To document the profile of patients presenting to the Prince Cyril Zulu Communicable Diseases Centre (CDC). Methods: A retrospective analysis of patient records. Results: A total of 79 738 new patients were investigated for tuberculosis by clinical, sputum examination and chest x-ray. 6802 cases were diagnosed, of which 79% had pulmonary TB, 3% had primary TB and 18% had other forms of TB. The mean and median age of the patients was 34 years and 31 years respectively, ranging from 5 to 72 years. 66% and 34% were men and women respectively. Majority were Black (88%) followed by Asians (8%), Coloured (2%) and White (2%). The treatment of 39%, 25% and 19% of patients was supervised by nurses at primary health care clinics, CDC and employer respectively Patients who were supervised by the CDC clinic (25/100), 75% completed their treatment at 6 months, whilst in 9% the treatment was interrupted at 1, 2, 10 weeks and in 4% of patients the treatment was interrupted at 4 months and in 2% the time of interruption was not known. Only 32% of patients were cured based on the sputum conversion to negative at 6 months. 10% of patients were transferred to hospitals for treatment. In 22% of patients the treatment was extended for variable time periods because of incomplete resolution. Conclusion: The cure rates are much lower than those aimed for by WHO and the current tuberculosis management strategies need to be strengthened to reduce the burden of TB in an area with a high prevalence of both of TB and HIV infection. Presenting author: Ayesha BM Kharsany, Fogarty AITRP, Private Bag 4, Congella, Durban, South Africa, Tel.: +27 31 4435, Fax: +27 31 4435, E-mail: [email protected] ThPeB7280 Saquinavir, ritonavir, didanosine, and lamivudine in a once daily regimen for HIV infection in patients with rifampin-containing antituberculosis treatment E. Ribera1, C. Azuaje1, F. Montero2, A. Soriano3, R.M. Lopez1, L. Pou 1, P. Domingo', J. Mallolas 1, F. Sanchez5, J.L. Lopez-Colomes5, J.M. Gatell3, A. Pahissa1. Hospital Vail d'Hebron, Infectious Diseases Service, Barcelona, Spain; 2Hospital de Sant Pau, Barcelona, Spain; 3Hospital Clinic Universitari, Barcelona, Spain; 4Hospital Clini Universitari, Barcelona, Spain; 5Hospital del Mar, Barcelona, Spain Background: The treatment of patients with HIV infection and tuberculosis (TB) is complex because of drug interactions occurring between rifamycines and PI/NNRTI. There is very little experience in the use of ritonavir (RTV)-saquinavir (SQV) and rifampin. Methods: Seventeen antiretroviral-naive HIV-infected patients with TB were recruited at four Hospitals in Barcelona. They received daily TB therapy with rifampin (600 mg), isoniazid, and pyrazinamide, with or without ethambutol. During the first two months patients were treated only with antiTB drugs. Then they started once-daily antiretroviral therapy with didanosine (400 or 250 mg), lamivudine (300 mg), ritonavir (200 mg) and saquinavir SG (1600 mg). Concentrations of all drugs were determined at steady-state by HPLC. Results: Median baseline viral load (VL) was 5.2 logl0copies/ml. After 4, 12 and 24 weeks median VL decreased 2.4, 3.4 and 3.5 logs, and HIV RNA was below 200 copies/ml in 4/17 (24%), 10/16 (63%), and 9/12 (75%) patients, respectively The CD4 cell count increased a median of 226 cells/mm3 after 24 weeks. PIs had to be discontinued because of side effects in two patients. SQV Cmin was quite similar in the same patient along the study time. Only one patient had a SQV Cmin lower than 0.05 ig/ml. The concentration-versus-time profiles showed wide variations, with the following median SQV PK parameters: AUCO-24h 13.2 ig/ml.h, Cmax 2.4 ig/ml, Tmax 3 h, and Cmin 0.17 ig/ml. There was a tendency to present higher concentrations of rifampin with SQV-RTV than without these drugs. Rifampin concentrations were very low in two patients, while with SQV-RTV they normalized. Conclusions: Our data shows that a once daily regimen of ddl/3TC/RTV/SQV can be administered to patients with rifampin-containing antiTB treatment. Patients had a favourable outcome, with TB cure, and consistent virologic and immunologic responses after 24 weeks. Toxicity profile was good. SQV and rifampin plasma levels were adequate. Presenting author: Esteban Ribera, Infectious Diseases Service, Hospital Vail d'Hebron, Paseo Vail d'Henron 119-129, 08035 Barcelona, Spain, Tel.: +34 932746090, Fax: +34 932746057, E-mail: [email protected] ThPeB7281I Clinical, virological and immunological outcome of TB/HIV Co-infected patients receiving antiretroviral therapy at a reference center in Argentina R. Quercia, G. Ben, C. Zala, S. Kaufman, M. Tocci, H. Perez, P. Cahn. Hospital Fernandez, Angel Peluffo 3932, C1202ABB, Buenos Aires, Argentina Background: Successful therapy of both TB and HIV meet similar obstacles: high pill burden, adherence, drug interactions and toxicity. Limited clinical data are available to support a therapeutic strategy in this setting. Objective: To asses clinical, virological and immunological outcome of HIV infected patients with active TB who were simultaneously treated for both TB and HIV. Methods: Chart review of HIV infected patients on treatment for TB who initiated antiretroviral therapy at a single reference center between 01/98 and 01/01. Results: 46 subjects (16 female), median age 34 (23-77) with pulmonary (54.3%) and extrapulmonany or disseminated (45.7%) TB received standard 4 drugs treatment, followed by 4 to 8 additional months of Isoniazid + Rifampin. Antiretroviral therapy was initiated simultaneously with TB therapy. ARVs included 2 NRTIs plus Abacavir (n=17); Nevirapine (n=9), Efavirenz (n=4) o PI (9). Safety labs and regular clinical visits were completed according to current practices at the treat ment center. Median plasma HIV RNA and CD4 cell count at initiation of ARV therapy was 111.675 copies/mL and 117 cells/mm3 respectively. At 48 w median plasma HIV RNA and CD4 count for the entire cohort was <50 copies/mL and 291 cells/mm3 respectively. In an intention-to-treat analysis, 69 % (32/46) patients had plasma HIV RNA below 50 copies/mL at 48 weeks. All 46 patients showed clinical improvement and/or negative AFB cultures. No treatment limiting toxicities were recorded.

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Abstract Book Vol. 2 [International Conference on AIDS (14th: 2002: Barcelona, Spain)]
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International AIDS Society
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Page 405
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2002
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abstracts (summaries)
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