RESUMO
OBJECTIVES: Use of ART containing HIV PIs has previously been associated with toxicity in subcutaneous adipose tissue (SAT), potentially contributing to the development of lipodystrophy and insulin resistance. However, the effect of PIs on SAT function in ART-naive patients independent of other ART classes is unknown. This study aimed to elucidate the effect of initiating PI-only ART on SAT function in ART-naive subjects. METHODS: In the HIVNAT-019 study, 48 HIV-infected, ART-naive Thai adults commencing PI-only ART comprising lopinavir/ritonavir/saquinavir for 24 weeks underwent assessments of fasting metabolic parameters and body composition. In a molecular substudy, 20 subjects underwent SAT biopsies at weeks 0, 2 and 24 for transcriptional, protein, mitochondrial DNA (mtDNA) and histological analyses. ClinicalTrials.gov registration number: NCT00400738. RESULTS: Over 24 weeks, limb fat increased (+416.4 g, Pâ=â0.023), coinciding with larger adipocytes as indicated by decreased adipocyte density in biopsies (-32.3 cells/mm2, Pâ=â0.047) and increased mRNA expression of adipogenesis regulator PPARG at week 2 (+58.1%, Pâ=â0.003). Increases in mtDNA over 24 weeks (+600 copies/cell, Pâ=â0.041), decreased NRF1 mRNA expression at week 2 (-33.7%, Pâ<â0.001) and increased COX2/COX4 protein ratio at week 24 (+288%, Pâ=â0.038) indicated improved mitochondrial function. Despite decreased AKT2 mRNA at week 2 (-28.6%, Pâ=â0.002) and increased PTPN1 mRNA at week 24 (+50.3%, Pâ=â0.016) suggesting insulin resistance, clinical insulin sensitivity [by homeostasis model assessment (HOMA-IR)] was unchanged. CONCLUSIONS: Initiation of PI-only ART showed little evidence of SAT toxicity, the changes observed being consistent with a return to health rather than contributing to lipodystrophy.
Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/uso terapêutico , Gordura Subcutânea/efeitos dos fármacos , Gordura Subcutânea/fisiologia , Adulto , Biópsia , DNA Mitocondrial/análise , Feminino , Perfilação da Expressão Gênica , Histocitoquímica , Humanos , Masculino , Proteoma/análise , TailândiaRESUMO
Sensitivity training of front-line African health care workers (HCWs) attending to men who have sex with men (MSM) is actively promoted through national HIV prevention programming in Kenya. Over 970 Kenyan-based HCWs have completed an eight-modular online training free of charge (http://www.marps-africa.org) since its creation in 2011. Before updating these modules, we performed a systematic review of published literature of MSM studies conducted in sub-Saharan Africa (sSA) in the period 2011-2014, to investigate if recent studies provided: important new knowledge currently not addressed in existing online modules; contested information of existing module topics; or added depth to topics covered already. We used learning objectives of the eight existing modules to categorise data from the literature. If data could not be categorised, new modules were suggested. Our review identified 142 MSM studies with data from sSA, including 34 studies requiring module updates, one study contesting current content, and 107 studies reinforcing existing module content. ART adherence and community engagement were identified as new modules. Recent MSM studies conducted in sSA provided new knowledge, contested existing information, and identified new areas of MSM service needs currently unaddressed in the online training.
Assuntos
Currículo , Infecções por HIV , Pessoal de Saúde/educação , Serviços de Saúde , Homossexualidade Masculina , Infecções por HIV/tratamento farmacológico , Homofobia , Humanos , Quênia , Masculino , Características de ResidênciaRESUMO
OBJECTIVE: To assess the feasibility of providing guideline-based cardiovascular disease (CVD) prevention care within the context of a community-based health insurance program (CBHI) in rural Nigeria. METHODS: A prospective operational cohort study was conducted in a primary healthcare clinic in rural Nigeria, participating in a CBHI program. The insurance program provided access to care and improved the quality of the clinics participating in the program, including CVD prevention guideline implementation. Insured adults at risk of CVD were consecutively included upon clinic attendance. The primary outcome was quality of care determined by scoring of quality indicators on patient files of the cohort, 1.5 year after guideline implementation. RESULTS: Of the 368 screened patients, 349 were included and 323 (93%) completed 1 year of follow-up. The majority of patients (331, 95%) had hypertension. Process indicators showed that 114/115 (99%) new hypertension cases had a record of CVD risk assessment and 249/333 (75%) eligible cases a record of lifestyle advice. Outcome indicators showed that in 292/328 (64%) hypertension cases, blood pressure was on target. Barriers to care included limited human resources, limited affordability of diagnostic tests and multidrug regimes for the healthcare provider, frequent doctor's appointments, and inefficient drug supplies. CONCLUSION: Implementation of CVD prevention care within the context of a CBHI program resulted in high-quality care in rural sub-Saharan Africa, comparable to high-income countries. However, guideline implementation was resource-intense and specific recommendations were not feasible. Simple models of care delivery are needed for rapid scale-up of CVD prevention services in sub-Saharan Africa.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Serviços de Saúde Comunitária/estatística & dados numéricos , Promoção da Saúde , Avaliação de Processos e Resultados em Cuidados de Saúde/estatística & dados numéricos , África Subsaariana , Idoso , Pressão Sanguínea , Determinação da Pressão Arterial , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Estudos de Viabilidade , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/terapia , Seguro Saúde , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Estudos Prospectivos , Saúde Pública , Fatores de Risco , População RuralRESUMO
OBJECTIVE: To assess the costs of cardiovascular disease (CVD) prevention care according to international guidelines, in a primary healthcare clinic in rural Nigeria, participating in a health insurance programme. METHODS: A micro-costing study was conducted from a healthcare provider perspective. Activities per patient per year (e.g., consultations, diagnostic tests) were based on clinical practice in the study clinic. Direct (e.g., staff, drugs) and indirect cost items (overheads) for each activity were measured. A cohort study, patient and staff observations, and interviews in the study clinic provided patient resource utilization data. Univariate sensitivity analyses were performed. Scenario analyses evaluated cost-saving options. The main outcome was the costs of CVD prevention care per patient per year. RESULTS: The costs of CVD prevention care were United States dollars (USD) 144 (range 130-158) per patient per year. Direct costs were USD 82 and indirect costs were USD 62. The main cost drivers were drugs (USD 39) and diagnostic tests (USD 36). The costs of hypertension care were USD 118 (107-132) and that of diabetes care USD 263 (236-289) per patient per year. A combination of task-shifting from doctors to nurses, reduction of appointment frequencies, and minimal organ damage screening would result in a direct cost reduction of 42%. CONCLUSION: This is the first study to report the costs of CVD prevention care in sub-Saharan Africa, based on prospectively collected operational data. The costs observed in our study are unaffordable in many countries in sub-Saharan Africa, highlighting the need for innovative financing mechanisms to fund CVD prevention care.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Serviços de Saúde Comunitária/economia , Promoção da Saúde/economia , Atenção Primária à Saúde , Doenças Cardiovasculares/economia , Estudos de Coortes , Redução de Custos , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Humanos , Seguro Saúde , Nigéria , População RuralRESUMO
BACKGROUND: With increased availability of paediatric combination antiretroviral therapy (cART) in resource limited settings, cART outcomes and factors associated with outcomes should be assessed. METHODS: HIV-infected children <15 years of age, initiating cART in Kigali, Rwanda, were followed for 18 months. Prospective clinical and laboratory assessments included weight-for-age (WAZ) and height-for-age (HAZ) z-scores, complete blood cell count, liver transaminases, creatinine and lipid profiles, CD4 T-cell count/percent, and plasma HIV-1 RNA concentration. Clinical success was defined as WAZ and WAZ >-2, immunological success as CD4 cells ≥500/mm3 and ≥25% for respectively children over 5 years and under 5 years, and virological success as a plasma HIV-1 RNA concentration <40 copies/mL. RESULTS: Between March 2008 and December 2009, 123 HIV-infected children were included. The median (interquartile (IQR) age at cART initiation was 7.4 (3.2, 11.5) years; 40% were <5 years and 54% were female. Mean (95% confidence interval (95%CI)) HAZ and WAZ at baseline were -2.01 (-2.23, -1.80) and -1.73 (-1.95, -1.50) respectively and rose to -1.75 (-1.98, -1.51) and -1.17 (-1.38, -0.96) after 12 months of cART. The median (IQR) CD4 T-cell values for children <5 and ≥5 years of age were 20% (13, 28) and 337 (236, 484) cells/mm3 respectively, and increased to 36% (28, 41) and 620 (375, 880) cells/mm3. After 12 months of cART, 24% of children had a detectable viral load, including 16% with virological failure (HIV-RNA>1000 c/mL). Older age at cART initiation, poor adherence, and exposure to antiretrovirals around birth were associated with virological failure. A third (33%) of children had side effects (by self-report or clinical assessment), but only 9% experienced a severe side effect requiring a cART regimen change. CONCLUSIONS: cART in Rwandan HIV-infected children was successful but success might be improved further by initiating cART as early as possible, optimizing adherence and optimizing management of side effects.
Assuntos
Antirretrovirais/administração & dosagem , Infecções por HIV , HIV-1 , Adesão à Medicação , Antirretrovirais/efeitos adversos , Contagem de Linfócito CD4 , Criança , Quimioterapia Combinada , Feminino , Seguimentos , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/patologia , Humanos , Masculino , Estudos Prospectivos , RNA Viral/sangue , Ruanda/epidemiologiaRESUMO
Since the discovery of HIV as the causative agent of AIDS in 1983/1984, remarkable progress has been made in finding antiretroviral drugs (ARVs) that are effective against it. A major breakthrough occurred in 1996 when it was found that triple drug therapy (HAART) could durably suppress viral replication to minimal levels. It was then widely felt, however, that HAART was too expensive and complex for low- and middle-income countries, and so, with the exception of a few of these countries, such as Brazil, a massive scale-up did not begin until the WHO launched its '3 by 5' initiative and sizeable funding mechanisms, such as the Global Fund to Fight AIDS, TB and Malaria and the US President's Emergency Plan for AIDS Relief (PEPFAR), came into existence. A pivotal enabler of the scale-up was a steady lowering of drug prices through entry of generic antiretrovirals, competition between generic manufacturers and the making of volume commitments. The WHO Prequalification of Medicines Programme and the Expedited Review Provision of the US Food and Drug Administration have been important for the assurance of quality standards. Antiretroviral drug development by research-based pharmaceutical companies continues, with several important innovative products, such as long-acting agents, in the pipeline.
Assuntos
Fármacos Anti-HIV/economia , Terapia Antirretroviral de Alta Atividade/economia , Indústria Farmacêutica/economia , Medicamentos Genéricos/economia , Infecções por HIV/tratamento farmacológico , Organização Mundial da Saúde/economia , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/provisão & distribuição , Países em Desenvolvimento , Medicamentos Genéricos/síntese química , Medicamentos Genéricos/provisão & distribuição , Guias como Assunto , Infecções por HIV/economia , Humanos , Cooperação Internacional , Controle de Qualidade , Equivalência TerapêuticaRESUMO
The concept of "treatment as prevention" has emerged as a means to curb the global HIV epidemic. There is, however, still ongoing debate about the evidence on when to start antiretroviral therapy in resource-poor settings. Critics have brought forward multiple arguments against a "test and treat" approach, including the potential burden of such a strategy on weak health systems and a presumed lack of scientific support for individual patient benefit of early treatment initiation. In this article, we highlight the societal and individual advantages of treatment as prevention in resource-poor settings. We argue that the available evidence renders the discussion on when to start antiretroviral therapy unnecessary and that, instead, efforts should be aimed at offering treatment as soon as possible.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Países em Desenvolvimento , HumanosRESUMO
Temporary cART during primary HIV-infection (PHI) did not select for drug resistance mutations after treatment interruption and did not affect the subsequent virological response to long-term cART. Our data demonstrate that fear of drug resistance development is not a valid argument to refrain from temporary early treatment during PHI.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Carga Viral/efeitos dos fármacos , Adulto , Esquema de Medicação , Feminino , Seguimentos , Infecções por HIV/genética , HIV-1/genética , Humanos , Assistência de Longa Duração , Masculino , RNA Viral/análiseRESUMO
BACKGROUND AND AIM: Vitamin D insufficiency plays an important role in liver fibrosis in hepatitis C virus (HCV)-infected patients. We assessed liver fibrosis by transient elastography and 25 hydroxy vitamin D [25(OH)D] status in HCV-infected patients, with (HIV/HCV) or without HIV co-infection (HCV) from Thailand. METHODS: Fibrosis stage was defined as mild (< 7.1 kPa); moderate (7.2-9.4 kPa); severe (9.5-14 kPa), and cirrhosis (> 14 kPa). Hypovitaminosis D was defined as 25(OH)D < 30 ng/mL. Logistic regression analyses were used to assess predictors for significant fibrosis. Serum 25(OH) D levels, HCV genotypes (GT), interleukin-28B (IL28B) and HCV-RNA were assessed. RESULTS: A total of 331 HCV and 130 HIV/HCV patients were enrolled (70% male, 35% people who inject drugs [PWIDs]). HCV GT distribution was as follows: GT3 47%, GT1 34%, GT6 17%. IL-28B CC genotype (rs12979860) were found in 88% of HIV/HCV and 85% of HCV. In HCV, liver fibrosis was mild in 56.5%; moderate in 18.4%; severe in 12.4%; and cirrhosis in 12.7%. In HIV/HCV, these figures were 30.6%, 27.8%, 17.6%, and 24.1%, respectively. Patients with significant fibrosis were more often male, older, with HIV infection, hypovitaminosis D, and less likely to be infected with GT6. Factors associated with significant fibrosis by multivariate analysis were HIV infection (adjusted odd ratio [95% confidential interval]: 2.67, 1.20-5.93), P = 0.016, Fib-4 score > 1.45 (6.30, 2.70-14.74), P < 0.001, and hypovitaminosis D (2.48, 1.09-5.67), P = 0.031. GT 6 was less likely to have advanced liver fibrosis (0.17, 0.05-0.65), P = 0.01. CONCLUSIONS: HIV infection, Fib-4 score > 1.45, and hypovitaminosis D are strong and independent predictors for the presence of advanced fibrosis in our HCV-infected patients. These data highlight the urgent need of HCV treatment and vitamin D supplement in resource-limited settings.
Assuntos
Alanina Transaminase/sangue , Coinfecção , Infecções por HIV/complicações , Hepatite C/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Deficiência de Vitamina D/complicações , Adulto , Povo Asiático , Biomarcadores/sangue , Técnicas de Imagem por Elasticidade , Feminino , Humanos , Cirrose Hepática/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Tailândia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/diagnósticoAssuntos
Fármacos Anti-HIV/administração & dosagem , Benzoxazinas/administração & dosagem , Desogestrel/administração & dosagem , Etinilestradiol/administração & dosagem , Infecções por HIV/tratamento farmacológico , Nevirapina/administração & dosagem , Alcinos , Fármacos Anti-HIV/sangue , Benzoxazinas/sangue , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/sangue , Ciclopropanos , Desogestrel/sangue , Relação Dose-Resposta a Droga , Interações Medicamentosas , Etinilestradiol/sangue , Feminino , Humanos , Nevirapina/sangue , Estudos ProspectivosRESUMO
IMPORTANCE Hypertension is a major public health problem in sub-Saharan Africa, but the lack of affordable treatment and the poor quality of health care compromise antihypertensive treatment coverage and outcomes. OBJECTIVE To report the effect of a community-based health insurance (CBHI) program on blood pressure in adults with hypertension in rural Nigeria. DESIGN, SETTING, AND PARTICIPANTS We compared changes in outcomes from baseline (2009) between the CBHI program area and a control area in 2011 through consecutive household surveys. Households were selected from a stratified random sample of geographic areas. Among 3023 community-dwelling adults, all nonpregnant adults (aged ≥18 years) with hypertension at baseline were eligible for this study. INTERVENTION Voluntary CBHI covering primary and secondary health care and quality improvement of health care facilities. MAIN OUTCOMES AND MEASURES The difference in change in blood pressure from baseline between the program and the control areas in 2011, which was estimated using difference-in-differences regression analysis. RESULTS Of 1500 eligible households, 1450 (96.7%) participated, including 564 adults with hypertension at baseline (313 in the program area and 251 in the control area). Longitudinal data were available for 413 adults (73.2%) (237 in the program area and 176 in the control area). Baseline blood pressure in respondents with hypertension who had incomplete data did not differ between areas. Insurance coverage in the hypertensive population increased from 0% to 40.1% in the program area (n = 237) and remained less than 1% in the control area (n = 176) from 2009 to 2011. Systolic blood pressure decreased by 10.41 (95% CI, -13.28 to -7.54) mm Hg in the program area, constituting a 5.24 (-9.46 to -1.02)-mm Hg greater reduction compared with the control area (P = .02), where systolic blood pressure decreased by 5.17 (-8.29 to -2.05) mm Hg. Diastolic blood pressure decreased by 4.27 (95% CI, -5.74 to -2.80) mm Hg in the program area, a 2.16 (-4.27 to -0.05)-mm Hg greater reduction compared with the control area, where diastolic blood pressure decreased by 2.11 (-3.80 to -0.42) mm Hg (P = .04). CONCLUSIONS AND RELEVANCE Increased access to and improved quality of health care through a CBHI program was associated with a significant decrease in blood pressure in a hypertensive population in rural Nigeria. Community-based health insurance programs should be included in strategies to combat cardiovascular disease in sub-Saharan Africa.
Assuntos
Anti-Hipertensivos/economia , Hipertensão/tratamento farmacológico , Cobertura do Seguro , Qualidade da Assistência à Saúde , Adulto , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Hipertensão/epidemiologia , Masculino , Nigéria/epidemiologia , Melhoria de Qualidade , População Rural , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To determine the long-term outcomes of treatment and prevalence of genotypic drug resistance in children and adolescents on combination antiretroviral therapy. METHODS: A cross-sectional study (September 2009 to October 2010) in which clinical, immunologic and virologic outcomes were assessed at a single-study visit and through patient records in a cohort of HIV-infected children and adolescents. Risk factors for clinical and immunologic responses and virologic outcome were evaluated using logistic regression, and the accuracy of clinical and immunologic criteria in identifying virologic failure was assessed. RESULTS: Four hundred twenty-four patients were enrolled with a median age of 10.8 years (range: 1.7-18.8) and a median duration on combination antiretroviral therapy of 3.4 years (range: 1.0-8.1). Thirty-three percent were stunted and 17% underweight. Eighty-four percent (95% confidence interval: 79-87) of children >5 years had CD4 ≥350 cells/mm and in 74% (95% confidence interval: 62-84) of younger children CD4% was ≥25. CD4 values and age at combination antiretroviral therapy initiation were independently associated with CD4 outcomes; 124 (29%) had HIV-1 RNA ≥1000 copies/mL, with no significant predictors. Sensitivity for weight-for-age and height-for-age and CD4 cells (<350/mm) remained under 50% (15-42%); CD4 cells showed the best specificity, ranging from 91% to 97%. Of 52 samples tested, ≥1 mutations were observed in 91% (nucleoside reverse transcriptase inhibitors) and 95% (non-nucleoside reverse transcriptase inhibitors); 1 to 2 thymidine analogue-associated mutations were detected in 16 (31%) and ≥3 thymidine analogue-associated mutations in 7 (13%). CONCLUSION: Nearly 1 in 3 children showed virologic failure, and >10% of the subgroup of children with treatment failure in whom genotyping was performed demonstrated multiple HIV drug resistance mutations. Neither clinical condition nor CD4 cells were good indicators for treatment failure.
Assuntos
Antirretrovirais/uso terapêutico , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Antirretrovirais/farmacologia , Peso Corporal , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Estudos Transversais , Farmacorresistência Viral/genética , Quimioterapia Combinada , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/genética , Humanos , Lactente , Masculino , Prevalência , Ruanda/epidemiologia , Resultado do TratamentoRESUMO
OBJECTIVES: To study the prevalence of target organ damage (TOD) in hypertensive adults in a general population in rural Nigeria, to assess determinants of TOD and the contribution of TOD screening to assess eligibility for antihypertensive treatment. METHODS: All adults diagnosed with hypertension (n=387) and a random sample (n=540) out of all nonhypertensive adults, classified during a household survey in 2009, had a blood pressure measurement and were invited for TOD (myocardial infarction, left ventricular hypertrophy, angina pectoris, kidney disease) screening in 2011. RESULTS: Participation in TOD screening was 51% (n=196) in respondents with hypertension and 33% (n=179) in those without hypertension. TOD prevalence in hypertensive and nonhypertensive adults was 32 and 15%, respectively. Hypertension severity was a strong determinant for TOD [grade 1 odds ratio (OR) 2.66, 95% confidence interval (CI)1.04-6.84; grade 2 OR 3.82, 95% CI 1.41-10.36]. Out of 196 hypertensive patients, 151 were untreated, of whom all grade 2 hypertensive patients (n=71) were eligible for treatment. Screening revealed TOD in 19 out of 80 grade 1 hypertensive respondents (24%), therefore also classifying them as eligible for treatment. TOD screening hypertensive nonrespondents had more severe hypertension than hypertensive respondents, which may have resulted in an underestimation of the true prevalence of TOD among adults with hypertension. CONCLUSION: A high prevalence of 32% TOD in hypertensive adults in rural Nigeria was observed. Almost a quarter of respondents with grade 1 hypertension were eligible for antihypertensive treatment based on TOD screening findings. As TOD screening is mostly unavailable in sub-Saharan Africa, we propose antihypertensive treatment for all patients with hypertension.
Assuntos
Hipertensão/complicações , Hipertensão/fisiopatologia , Adolescente , Adulto , Idoso , Angina Pectoris/epidemiologia , Angina Pectoris/etiologia , Estudos Transversais , Feminino , Humanos , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/etiologia , Nefropatias/epidemiologia , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Nigéria/epidemiologia , Prevalência , Fatores de Risco , População Rural , Adulto JovemRESUMO
BACKGROUND: Vitamin D insufficiency plays an important role in the development of fibrosis in chronic liver disease. METHODS: This was a cross-sectional study from Thailand. Liver fibrosis was assessed by transient elastography. Serum 25 hydroxyvitamin D (25[OH]D)<30 ng/ml was defined as hypovitaminosis D. 25(OH)D was assessed prior to and following tenofovir disoproxil fumarate (TDF). Factors related to 25(OH)D levels were determined by logistic regression analysis. RESULTS: A total of 158 HIV-HBV-coinfected patients (32% female, median age 43 years) were included. Overall, liver disease was mild with 13.4% having a fibrosis score (FS) of 7.1-14 kPa and 2% with a FS>14 kPa. Median (IQR) duration on TDF was 5 years (4-7). The median estimated glomerular filtration rate was 96.9 ml/min/1.73 m(2). The median (IQR) serum 25(OH)D levels prior to and following TDF were 24.8 ng/ml (21.3-30.6) and 22.8 ng/ml (18.0-27.7), respectively; P≤0.001). The proportion of patients with hypovitaminosis D significantly increased from 72.2% (95% CI 64.7, 78.6) prior to TDF to 84.2% (95% CI 77.7, 89.0) after taking TDF (P=0.01). Factors associated with hypovitaminosis D by multivariate analysis were female sex (adjusted OR 3.8, 95% CI 1.1, 13.7; P=0.038) and duration of antiretroviral therapy (ART)>5 years (OR 3.3, 95% CI 1.2, 8.8; P=0.017). Vitamin D levels were not associated with significant liver fibrosis. CONCLUSIONS: Although our HIV-HBV-coinfected patients live in the tropics, there was a high prevalence of hypovitaminosis D, especially in female patients and those receiving prolonged ART. Since HIV-HBV-coinfection requires long-term use of the HBV-active drug, TDF, which can also contribute to bone loss, routine vitamin D assessment and supplementation as necessary should be considered.
Assuntos
Coinfecção , Infecções por HIV/sangue , Hepatite B/sangue , Vitamina D/análogos & derivados , Adulto , Terapia Antirretroviral de Alta Atividade , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Humanos , Hipofosfatemia/complicações , Testes de Função Renal , Túbulos Renais Proximais/fisiopatologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tailândia , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Adulto JovemRESUMO
Physiological effects of aging make the older population more susceptible to adverse drug events and drug-drug interactions. We evaluated the impact of aging and gender on the pharmacokinetics (PK) of atazanavir/ritonavir (ATV/r) 300/100 mg once daily (qd) in 22 well-suppressed HIV-infected patients. This was a 24-h intensive PK study. Subjects were HIV-1-infected adults aged ≥18 years with HIV RNA <50 copies/ml and treated with ATV/r 300/100 mg once daily plus two nucleoside reverse transcriptase inhibitors (NRTIs) for at least 2 weeks. Atazanavir and ritonavir plasma concentrations were measured by validated high-performance liquid chromatography (HPLC). Plasma PK parameters were calculated using noncompartmental methods. Since 50% of the patients were older than 42 years, age 42 was selected as the cut-off point for the older (>42 years) group. Gender, weight, duration of ATV/r therapy, and proportion treated with tenofovir disoproxil fumarate (TDF)-containing regimens did not differ between both groups. Patients from the aging group had a reduced creatinine clearance (91 versus 76 ml/min). The older group had a higher atazanavir exposure with median AUC(0-24) 71.2 vs. 53.1 mg·h/liter, C(max) 8.5 vs. 5.5 mg/liter, and C(trough) 1.17 vs. 0.78 mg/liter, and slower apparent clearance (3.5 vs. 4.8 liter/h). Ten patients (91%) from the older group and 36% from the younger group had ATV C(trough) levels higher than the proposed upper limit for toxicity of 0.85 mg/liter. Females had a lower body weight (BW) (46 versus 63 kg) than the males, but atazanavir concentrations in females were greater. However, in multivariate analysis, older age was the only significant predictor for higher atazanavir concentrations. Parameter estimate for age and atazanavir AUC after adjusting for gender and BW was 2.17 (95% CI 1.01-3.33). That is, for every year increase in age, AUC increases by approximately 2 mg·h/liter. Age seems to be an important factor influencing atazanavir pharmacokinetics. Patients from the aging group appeared to have higher atazanavir exposure compared to the younger group. Further PK explorations of ATV in the extremely aged population are warranted.
Assuntos
Fatores Etários , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/sangue , Oligopeptídeos/sangue , Piridinas/sangue , Fatores Sexuais , Adulto , Ásia , Sulfato de Atazanavir , Feminino , Infecções por HIV/sangue , Inibidores da Protease de HIV/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/uso terapêutico , Piridinas/uso terapêuticoRESUMO
BACKGROUND: There is a high incidence of tuberculosis (TB) early after antiretroviral therapy (ART) initiation. This historical cohort study evaluated the association of efavirenz (EFV) compared to nevirapine (NVP) with post-ART TB among patients initiated on first-line ART from 2005 to 2009 in a large, urban HIV clinic in Uganda. METHODS: Hazard ratios (HR) for developing TB were computed using multivariable Cox proportional hazards models with inverse weighting of the probability of being prescribed NVP or EFV (calculated by a multivariable logistic regression model), stratifying by baseline CD4+ T-cell count. Adjustment for time-updated CD4+ T-cell count, restriction of the analysis to patients remaining in follow-up and a TB-free survival analysis were performed as sensitivity analyses. RESULTS: ART was initiated in 5,797 patients; 66% were women with a mean age of 37 years (SD 9) and a median baseline CD4+ T-cell count of 117 cells/mm3 (IQR 43-182). Overall, 60% (n = 3,484) were initiated on NVP and 40% (n = 2,313) on EFV. In the first 2 years of ART, 377 patients developed TB. The use of EFV compared to NVP was independently associated with higher TB incidence in patients with a baseline CD4+ T-cell count < 100 cells/mm3 (HR 2.05 [95% CI 1.29, 3.27]; P = 0.003), but not at higher CD4+ T-cell counts (HR 0.71 [95% CI 0.39, 1.31]; P = 0.428). These estimates were robust to all sensitivity analyses. CONCLUSIONS: There was a higher incidence of TB in patients with baseline CD4+ T-cell counts < 100 cells/mm3 initiated on EFV compared to those initiated on NVP. Further research in a trial setting or a larger multisite observational cohort is needed to confirm these findings.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/efeitos adversos , Infecções por HIV/tratamento farmacológico , Nevirapina/efeitos adversos , Tuberculose Pulmonar/etiologia , Adulto , Alcinos , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Estudos de Coortes , Comorbidade , Ciclopropanos , Feminino , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Modelos de Riscos Proporcionais , Fatores de Risco , Análise de Sobrevida , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/mortalidade , Uganda/epidemiologia , Carga Viral/efeitos dos fármacosRESUMO
BACKGROUND: Prisoners are at high risk of developing tuberculosis (TB), causing morbidity and mortality. Prison facilities encounter many challenges in TB screening procedures and TB control. This review explores screening practices for detection of TB and describes limitations of TB control in prison facilities worldwide. METHODS: A systematic search of online databases (e.g., PubMed and Embase) and conference abstracts was carried out. Research papers describing screening and diagnostic practices among prisoners were included. A total of 52 articles met the inclusion criteria. A meta-analysis of TB prevalence in prison facilities by screening and diagnostic tools was performed. RESULTS: The most common screening tool was symptom questionnaires (63·5%), mostly reporting presence of cough. Microscopy of sputum with Ziehl-Neelsen staining and solid culture were the most frequently combined diagnostic methods (21·2%). Chest X-ray and tuberculin skin tests were used by 73·1% and 50%, respectively, as either a screening and/or diagnostic tool. Median TB prevalence among prisoners of all included studies was 1,913 cases of TB per 100,000 prisoners (interquartile range [IQR]: 332-3,517). The overall annual median TB incidence was 7·0 cases per 1000 person-years (IQR: 2·7-30·0). Major limitations for successful TB control were inaccuracy of diagnostic algorithms and the lack of adequate laboratory facilities reported by 61·5% of studies. The most frequent recommendation for improving TB control and case detection was to increase screening frequency (73·1%). DISCUSSION: TB screening algorithms differ by income area and should be adapted to local contexts. In order to control TB, prison facilities must improve laboratory capacity and frequent use of effective screening and diagnostic tools. Sustainable political will and funding are critical to achieve this.
Assuntos
Tosse/diagnóstico , Ensaio de Proficiência Laboratorial/organização & administração , Mycobacterium tuberculosis/isolamento & purificação , Prisões/economia , Tuberculose Pulmonar/diagnóstico , Tosse/patologia , Bases de Dados Bibliográficas , Feminino , Humanos , Incidência , Ensaio de Proficiência Laboratorial/economia , Masculino , Prevalência , Prisioneiros/estatística & dados numéricos , Radiografia Torácica , Escarro/microbiologia , Inquéritos e Questionários , Teste Tuberculínico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Recursos HumanosRESUMO
BACKGROUND: Effective contraception has been widely promoted for HIV-positive women. However, there are limited data on the interactions between combined hormonal contraceptives and nonnucleoside reverse transcriptase inhibitors . METHODS: This study assessed the steady-state contraceptive effectiveness and safety of combined oral contraceptive (COC) containing 0.150 mg desogestrel /0.030 mg ethinyl estradiol with either nevirapine (NVP) or efavirenz (EFV) in 34 HIV-positive women. The targeted level for contraceptive effectiveness was endogenous progesterone level < 3.0 ng/mL. We measured NVP/EFV plasma concentrations 12 hours after administration (C12) with and without COC. The desired therapeutic levels were >3.1 mg/L for NVP and 1.0-4.0 mg/L for EFV, respectively. RESULTS: All 18 subjects in the NVP group had serum progesterone <1.0 ng/mL. Four of 16 subjects (25%) in the EFV group had serum progesterone >1.0 ng/mL, including 3 subjects with >3.0 ng/mL (might indicate ovulation). The difference in progesterone levels between the 2 groups was statistically significant (P = 0.04). The median C12 of NVP increased insignificantly by 17% with COC; the median C12 of EFV decreased significantly (P = 0.02) by 22%. In 3 of 16 subjects (19%) in the EFV group, C12 of EFV dropped below 1.0 mg/L. CONCLUSIONS: In contrast to NVP, coadministrating desogestrel/ethinyl estradiol containing COC with EFV was associated with unfavorable progesterone and antiretroviral levels. Our results suggest that NVP may be superior to EFV when used with COC in HIV-positive women.