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BACKGROUND: Women infected with human immunodeficiency virus (HIV) have higher rates of persistent infection with high-risk human papillomavirus (hr-HPV) and cervical and anal dysplasia. We describe the epidemiology of hr-HPV, and cervical and anal intra-epithelial abnormalities in HIV-infected women in Thailand. METHODS: HIV-infected women aged 18-49 years, either HAART-naïve or -experienced, were enrolled in Bangkok, Thailand. A demographic and sexual-risk behaviour questionnaire was administered and a pelvic examination with colposcopy was performed on every woman. Cervical and anal samples were tested for cytology and HPV genotyping. RESULTS: A total of 256 women were enrolled with a median [interquartile range (IQR)] age of 35 (32-40) years. Ninety (35.2%) had detectable cervical hr-HPV. Being post-menopausal was associated with increased risk for cervical hr-HPV, while years since HIV diagnosis and plasma HIV RNA <40 copies/mL were significantly associated with decreased risk in multivariable regression analyses. Abnormal cervical cytology was detected in 6.3%. Cervical biopsies that were taken from 99 women (39.3%) owing to abnormalities seen during colposcopy showed cervical intra-epithelial neoplasia (CIN) in 22.6%. The sensitivity of cervical cytology to detect CIN2+ was 10.0%. Among 102 women enrolled in the anal substudy, 18.8% had anal HPV infection and 11.1% had anal hr-HPV. Two women had abnormal anal cytology. CONCLUSION: We found cervical and anal hr-HPV in 35.2% and 11.1% of Thai HIV-infected women, respectively. Moreover, the observed poor agreement between cervical cytology and histology results could indicate current cervical cancer screening programs for HIV-infected women might not be optimal for the detection of pre-neoplastic lesions.
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OBJECTIVE: The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in a cohort of HIV-infected Rwandan children and adolescents on combination antiretroviral therapy (cART), and the success rate of HBV vaccination in those children found to be HBV negative. METHODS: HIV-infected children and adolescents (age 8-17 years) receiving cART with CD4 T-cells count ≥200 cells/mm and/or ≥15% and without prior HBV vaccination (by history, vaccination cards and clinic records) underwent serologic testing for past (negative HBV surface antigen [HBsAg] with positive antibody to HBV core antigen [cAb] and to HBsAg [anti-HBs]) or active HBV infection (positive HBsAg). Children with any positive HBV serologic tests were excluded from further vaccination; all others completed 3 HBV immunizations with 10 µg of ENGERIX-B. Anti-HBs titer was measured 4-6 weeks after the last immunization. RESULTS: Of 88 children, 6 (7%) children had active HBV infection and 8 (9%) had past HBV infection. The median (interquartile range) age, CD4 T-cell count and cART duration were 12.3 (10.1-13.9) years, 626 (503 to 942) cells/mm and 1.9 (1.5-2.7) years, respectively. Seventeen children had detectable plasma HIV-1 RNA. Seventy-3 children completed 3 immunizations with median (interquartile range) postimmunization anti-HBs concentration of 151 mIU/mL (1.03-650). Overall, 52 children (71%, 95% confidence interval: 61-82) developed a protective anti-HBs response. HIV-1 RNA and CD4 T-cell count were independent predictors of a protective anti-HBs response. Protective anti-HBs response was achieved in 82% of children with undetectable HIV-1 RNA and 77% with CD4 T cells ≥350/mm. CONCLUSIONS: The substantial HBV prevalence in this cohort suggests that HIV-infected Rwandan children should be screened for HBV before cART initiation. HIV viral suppression and CD4 T cells ≥350/mm favored the likelihood of a protective response after HBV vaccination.
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Antirretrovirais/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Vacinas contra Hepatite B/imunologia , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/prevenção & controle , Adolescente , Criança , Estudos de Coortes , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Humanos , Masculino , Prevalência , Estudos Prospectivos , Ruanda/epidemiologiaRESUMO
BACKGROUND: Generic products reduce the costs of HIV treatment. Few generic second-line antiretroviral products are available. We assessed pharmacokinetics, safety and efficacy of generic lopinavir/ritonavir (LPV/r) produced by the Government Pharmaceutical Organization (GPO) of Thailand in Thai HIV-infected adults. METHODS: This was a single-arm prospective study. Patients with plasma HIV-1 RNA<50 copies/ml for ≥24 weeks, who were protease inhibitor (PI)-naive or experienced, were eligible. Patients started generic LPV/r tablets, 400/100 mg twice daily. At week 4, therapeutic drug monitoring was performed and analysed by validated HPLC. In patients using Kaletra(®) (Abbott Laboratories, North Chicago, IL, USA) soft gel capsules (SGC) or generic LPV/r tablets produced by Mylan (Canonsburg, PA, USA; formerly Matrix, Hyderabad, India) prior to study entry, we compared the plasma minimum concentrations (Cmin) of the different formulations. Plasma HIV-1 RNA and safety were assessed until week 48. RESULTS: A total of 70 patients (32 males) were enrolled. Mean (sd) age was 40.7 (7.9) years and mean (sd) body weight was 60.3 (9.0) kg. Before study entry, all patients were virologically suppressed using a PI-based regimen; 62 (88.6%) were using LPV/r (Kaletra(®) SGC n=22 and Mylan generic tablets n=40). Mean (sd) Cmin of GPO lopinavir and GPO ritonavir at week 4 were 7.1 (2.9) mg/l and 0.39 (0.21) mg/l, respectively, and not significantly different from the Cmin when taking Kaletra(®) SGC or Mylan generic tablets. After 48 weeks, 95.6% of patients maintained plasma HIV-1 RNA<50 copies/ml. Four grade 3 and no grade 4 adverse events were reported. CONCLUSIONS: Generic LPV/r showed adequate levels, good tolerability and excellent 48-week efficacy.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Contagem de Linfócito CD4 , Combinação de Medicamentos , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Lopinavir/efeitos adversos , Lopinavir/farmacocinética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ritonavir/efeitos adversos , Ritonavir/farmacocinética , Tailândia , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND: Nevirapine (NVP) is often prescribed once daily in clinical practice in combination with a once daily nucleoside backbone. We investigated the relationship of NVP dosing with safety and efficacy. METHODS: Patients from the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort study, Canadian HAART Observational Medical Evaluation and Research (HOMER) cohort and Swiss HIV Cohort Study (SHCS) using NVP-based combination therapy either once daily or twice daily were included. Risk factors for discontinuing NVP because of hypersensitivity reactions (HSRs) were investigated using multivariate logistic regression. Risk factors for virological failure 96 weeks after NVP initiation were identified using logistic regression and Cox models. RESULTS: Of 5,636 patients (774 once daily and 4,862 twice daily), 268 (4.8%) discontinued NVP because of HSR between 2 and 18 weeks. Logistic regression showed that, compared with patients with detectable HIV type-1 (HIV-1) RNA starting twice-daily NVP, there was a significantly higher risk of discontinuation of once-daily NVP because of HSR in patients with detectable HIV-1 RNA at the start of NVP (odds ratio [OR] 1.52; P=0.04), whereas the risk was actually significantly lower in patients starting once-daily NVP with undetectable HIV-1 RNA (OR 0.44; P=0.04). Cox models showed that risk of virological failure was not different for twice- versus once-daily NVP in treatment-naive patients (twice-daily versus once-daily hazard ratio [HR] 1.01; P=0.95), treatment-experienced patients experiencing treatment failure (twice-daily versus once-daily HR 1.22; P=0.30) or patients with undetectable HIV-1 RNA simplifying treatment with NVP (twice-daily versus once-daily HR 1.29; P=0.30). CONCLUSIONS: Initiation of a once-daily NVP-based regimen in patients with suppressed viraemia carries a low risk of treatment-limiting HSR. Once- or twice-daily NVP-based regimens appear to have similar antiretroviral efficacy.
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Fármacos Anti-HIV , Infecções por HIV/tratamento farmacológico , Nevirapina , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Estudos de Coortes , Esquema de Medicação , Hipersensibilidade a Drogas/etiologia , Quimioterapia Combinada , Feminino , HIV-1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Nevirapina/administração & dosagem , Nevirapina/efeitos adversos , Organofosfonatos/uso terapêutico , Estudos Retrospectivos , Tenofovir , Resultado do TratamentoRESUMO
OBJECTIVE: An important pending question is whether temporary highly active antiretroviral therapy during primary HIV infection can influence viral rebound dynamics and the subsequently established viral setpoint, through preservation and enhancement of HIV-1-specific immune responses, or through other mechanisms. METHODS: We included all patients from two prospective studies who underwent a single treatment interruption while being well suppressed on highly active antiretroviral therapy. One group started highly active antiretroviral therapy during primary HIV infection, and the other group started it during chronic HIV infection with CD4 cell counts above 350 cells/microl. Data were collected up to 48 weeks from treatment interruption. The median time to viral rebound was analysed for three levels of viraemia: 50, 500 and 5000 copies HIV-RNA/ml plasma. RESULTS: The median time to viral rebound was significantly longer in primary HIV infection patients (n = 24) than in chronic HIV infection patients (n = 46): 8 versus 4 weeks (P < 0.001 for all three endpoints). In two primary HIV infection patients, no rebound of plasma HIV-1 RNA over 50 copies/ml occurred. In the first 4 weeks after treatment interruption, CD4+ T-cell counts declined with a median of -5.0 cells/microl blood per week in the primary HIV infection group and -45 cells/microl blood per week in the chronic HIV infection group (P < 0.05). From week 4 to 48, the decline in CD4+ T-cell count was similar in both groups. CONCLUSION: Plasma viral load and CD4 dynamics after a single interruption of highly active antiretroviral therapy were different for primary HIV infection and chronic HIV infection patients. Viral rebound is delayed or absent and early CD4 cell count decline after treatment interruption is less pronounced in primary HIV infection patients.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/fisiologia , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Doença Crônica , Progressão da Doença , Esquema de Medicação , Feminino , Infecções por HIV/imunologia , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/sangue , Estatísticas não Paramétricas , Carga Viral , Replicação ViralRESUMO
We studied the dynamics of CD4 cell counts after the interruption of virologically successful highly active antiretroviral therapy (HAART) in 139 patients. Changes in CD4 cell counts during HAART interruption followed a biphasic pattern: an initial rapid decline during the first month followed by a slow decrease. During 48 weeks of follow-up mean CD4 cell counts remained just above the mean pre-HAART level. This limits the feasibility of structured treatment interruptions for patients with low nadir CD4 cell counts.