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1.
BMC Infect Dis ; 19(1): 914, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664933

RESUMO

BACKGROUND: Programmatic data on the baseline risk of tuberculosis in people living with HIV (PLHIV) are needed to evaluate long-term effectiveness of the ongoing isoniazid preventive therapy (IPT) roll-out in India. METHODS: We estimated the incidence rate and risk factors of tuberculosis disease in adult PLHIV initiating first- and second-line anti-retroviral therapy (ART) prior to widespread IPT in a public ART center in Pune, India. RESULTS: 4067 participants contributing 5205.7 person-years of follow-up on first-line ART and 871 participants contributing 1031.7 person-years of follow-up on second-line ART were included in the analysis. The incidence rate of tuberculosis was 4.39 cases (95%CI 3.86-5.00) per 100 person-years on first-line ART and 1.64 cases (95%CI 1.01-2.63) per 100 person-years on second-line ART (p < 0.001). After adjusting for competing risks, male sex (aSHR = 1.33, 95%CI 1.02-1.74, p = 0.03), urban residence (aSHR = 1.53, 95%CI 1.13-2.07, p = 0.006) and CD4+ counts < 350 cells/mm3 (aSHR = 3.06 vs CD4 > 350 cells/mm3, 95%CI 1.58-5.94, p < 0.001) at ART initiation were associated with higher risk of tuberculosis independent of ART regimen. CONCLUSION: Risk of tuberculosis was lower in PLHIV receiving second-line ART compared to first-line ART. Prioritizing IPT in PLHIV with low CD4+ counts, urban residence and in males may further mitigate the risk of tuberculosis during ART.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Tuberculose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adolescente , Adulto , Antituberculosos/uso terapêutico , Contagem de Linfócito CD4 , Feminino , Seguimentos , Humanos , Incidência , Índia/epidemiologia , Isoniazida/uso terapêutico , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Tuberculose/prevenção & controle , População Urbana , Adulto Jovem
2.
N Engl J Med ; 381(14): 1333-1346, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31577875

RESUMO

BACKGROUND: The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown. METHODS: In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years. RESULTS: A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], -4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, -0.39; 95% CI, -1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, -0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9). CONCLUSIONS: The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038.).


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Isoniazida/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Tuberculose/prevenção & controle , Adolescente , Adulto , Antituberculosos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Isoniazida/efeitos adversos , Testes de Função Hepática , Período Pós-Parto , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Adulto Jovem
3.
BMC Infect Dis ; 19(1): 685, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382917

RESUMO

BACKGROUND: HIV-infected children are at a higher risk of Invasive Pneumococcal Disease (IPD) and its mortality, even in the era of antiretroviral therapy. Therefore, an effective vaccination strategy would be beneficial. To investigate the effectiveness of Pneumococcal Conjugate Vaccination (PCV) against IPD among HIV-Infected and HIV-Uninfected Children through a systematic review and meta-analysis. METHODS: Observational studies and randomized trials on 7 years old or older children were searched in the Cochrane Library, Web of Science core collection, Embase, Medline/PubMed, and Google Scholar. Critical appraisal was done using the Cochrane risk of bias tool and the Newcastle-Ottawa quality assessment form. Effectiveness and efficacy of at least one dose of PCV was investigated among children with and without HIV considering subgroups of pneumococcal serotypes. We meta-analyzed the effect sizes using random-effects modeling. RESULTS: Efficacy of PCV was estimated as 45.0% (31.2, 56.1) and 52.6% (25.7, 69.8) among HIV-infected and HIV-uninfected children, respectively. Effectiveness of PCV among HIV-infected children as - 6.2% (- 67.6, 32.7) was significantly lower than HIV-uninfected children 65.1% (47.3, 76.9). Effectiveness of PCV among HIV-infected children for IPDs caused by vaccine serotypes was estimated as 7.7(- 66.7, 48.9), and for IPDs caused by non-vaccine serotypes was estimated as - 402.8(- 1856, - 29.2). CONCLUSION: Unlike the evidence on the efficacy of PCV against IPD among both of HIV-infected and HIV-uninfected children, its effectiveness against IPD among HIV-infected children is much less limited. REVIEW REGISTRATION: The study protocol was registered at PROSPERO (registration ID: CRD42018108187).


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/farmacologia , Vacinas Conjugadas/farmacologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Criança , Pré-Escolar , Humanos , Lactente , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Vacinação
4.
Top Antivir Med ; 27(1): 34-40, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31137001

RESUMO

The 2019 Conference on Retroviruses and Opportunistic Infections provided a considerable amount of new information on the progress in implementation of strategies to reduce morbidity and mortality from complications and coinfections that occur in people with HIV infection, and on the clinical management of these important problems. This review will address new insights into the prevention and treatment of tuberculosis, fungal infections, sexually transmitted infections, malignancies, and a range of metabolic complications and noncommunicable diseases.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Coinfecção/epidemiologia , Infecções por HIV/complicações , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Coinfecção/prevenção & controle , Humanos , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/prevenção & controle , Micoses/diagnóstico , Micoses/tratamento farmacológico , Micoses/prevenção & controle , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/prevenção & controle
5.
BMC Infect Dis ; 19(1): 261, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30876400

RESUMO

BACKGROUND: The WHO guidelines for the management of advanced HIV disease recommend a package of care consisting of rapid initiation of antiretroviral therapy (ART), enhanced screening and diagnosis of tuberculosis (TB) and cryptococcal meningitis, co-trimoxazole prophylaxis, isoniazid preventive therapy (IPT), fluconazole pre-emptive therapy, and adherence support. The goals of this study were to determine the prevalence of advanced HIV disease among individuals initiating ART in Senegal, to identify predictors of advanced disease, and to evaluate adherence to the WHO guidelines. METHODS: This study was conducted among HIV-positive individuals initiating ART in Dakar and Ziguinchor, Senegal. Clinical evaluations, laboratory analyses, questionnaires and chart review were conducted. Logistic regression was used to identify predictors of advanced disease. RESULTS: A total of 198 subjects were enrolled; 70% were female. The majority of subjects (71%) had advanced HIV disease, defined by the WHO as a CD4 count < 200 cells/mm3 or clinical stage 3 or 4. The median CD4 count was 185 cells/mm3. The strongest predictors of advanced disease were age ≥ 35 (OR 5.80, 95%CI 2.35-14.30) and having sought care from a traditional healer (OR 3.86, 95%CI 1.17-12.78). Approximately one third of subjects initiated ART within 7 days of diagnosis. Co-trimoxazole prophylaxis was provided to 65% of subjects with CD4 counts ≤350 cells/mm3 or stage 3 or 4 disease. TB symptom screening was available for 166 subjects; 54% reported TB symptoms. Among those with TB symptoms, 39% underwent diagnostic evaluation. Among those eligible for IPT, one subject received isoniazid. No subjects underwent CrAg screening or received fluconazole to prevent cryptococcal meningitis. CONCLUSIONS: This is the first study to report an association between seeking care from a traditional healer and presentation with WHO defined advanced disease in sub-Saharan Africa. Given the widespread use of traditional healers in sub-Saharan Africa, future studies to further explore this finding are indicated. Although the majority of individuals in this study presented with advanced disease and warranted management according to WHO guidelines, there were numerous missed opportunities to prevent HIV-associated morbidity and mortality. Programmatic evaluation is needed to identify barriers to implementation of the WHO guidelines and enhanced funding for operational research is indicated.


Assuntos
Antirretrovirais/uso terapêutico , Fidelidade a Diretrizes/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adulto , Contagem de Linfócito CD4 , Feminino , HIV , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Humanos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Prevalência , Fatores de Risco , Senegal/epidemiologia
6.
N Engl J Med ; 380(11): 1001-1011, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30865794

RESUMO

BACKGROUND: Tuberculosis is the leading killer of patients with human immunodeficiency virus (HIV) infection. Preventive therapy is effective, but current regimens are limited by poor implementation and low completion rates. METHODS: We conducted a randomized, open-label, phase 3 noninferiority trial comparing the efficacy and safety of a 1-month regimen of daily rifapentine plus isoniazid (1-month group) with 9 months of isoniazid alone (9-month group) in HIV-infected patients who were living in areas of high tuberculosis prevalence or who had evidence of latent tuberculosis infection. The primary end point was the first diagnosis of tuberculosis or death from tuberculosis or an unknown cause. Noninferiority would be shown if the upper limit of the 95% confidence interval for the between-group difference in the number of events per 100 person-years was less than 1.25. RESULTS: A total of 3000 patients were enrolled and followed for a median of 3.3 years. Of these patients, 54% were women; the median CD4+ count was 470 cells per cubic millimeter, and half the patients were receiving antiretroviral therapy. The primary end point was reported in 32 of 1488 patients (2%) in the 1-month group and in 33 of 1498 (2%) in the 9-month group, for an incidence rate of 0.65 per 100 person-years and 0.67 per 100 person-years, respectively (rate difference in the 1-month group, -0.02 per 100 person-years; upper limit of the 95% confidence interval, 0.30). Serious adverse events occurred in 6% of the patients in the 1-month group and in 7% of those in the 9-month group (P = 0.07). The percentage of treatment completion was significantly higher in the 1-month group than in the 9-month group (97% vs. 90%, P<0.001). CONCLUSIONS: A 1-month regimen of rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing tuberculosis in HIV-infected patients. The percentage of patients who completed treatment was significantly higher in the 1-month group. (Funded by the National Institute of Allergy and Infectious Diseases; BRIEF TB/A5279 ClinicalTrials.gov number, NCT01404312.).


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antituberculosos/administração & dosagem , Infecções por HIV/tratamento farmacológico , Isoniazida/administração & dosagem , Tuberculose Latente/tratamento farmacológico , Rifampina/análogos & derivados , Tuberculose/prevenção & controle , Adulto , Antituberculosos/efeitos adversos , Contagem de Linfócito CD4 , Esquema de Medicação , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Humanos , Isoniazida/efeitos adversos , Tuberculose Latente/complicações , Masculino , Adesão à Medicação , Rifampina/administração & dosagem , Rifampina/efeitos adversos
8.
PLoS One ; 14(1): e0210105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30629619

RESUMO

BACKGROUND: Cryptococcal meningitis accounts for 15% of AIDS-related mortality. Cryptococcal antigen (CrAg) is detected in blood weeks before onset of meningitis, and CrAg positivity is an independent predictor of meningitis and death. CrAg screening for patients with advanced HIV and preemptive treatment is recommended by the World Health Organization, though implementation remains limited. Our objective was to evaluate costs and mortality reduction (lives saved) from a national CrAg screening program across Uganda. METHODS: We created a decision analytic model to evaluate CrAg screening. CrAg screening was considered for those with a CD4<100 cells/µL per national and international guidelines, and in the context of a national HIV test-and-treat program where CD4 testing was not available. Costs (2016 USD) were estimated for screening, preemptive therapy, hospitalization, and maintenance therapy. Parameter assumptions were based on large prospective CrAg screening studies in Uganda, and clinical trials from sub Saharan Africa. CrAg positive (CrAg+) persons could be: (a) asymptomatic and thus eligible for preemptive treatment with fluconazole; or (b) symptomatic with meningitis with hospitalization. RESULTS: In the base case model for 1 million persons with a CD4 test annually, 128,000 with a CD4<100 cells/µL were screened, and 8,233 were asymptomatic CrAg+ and received preemptive therapy. Compared to no screening and treatment, CrAg screening and treatment in the base case cost $3,356,724 compared to doing nothing, and saved 7,320 lives, for a cost of $459 per life saved, with the $3.3 million in cost savings derived from fewer patients developing fulminant meningitis. In the scenario of a national HIV test-and-treat program, of 1 million HIV-infected persons, 800,000 persons were screened, of whom 640,000 returned to clinic, and 8,233 were incident CrAg positive (CrAg prevalence 1.4%). The total cost of a CrAg screening and treatment program was $4.16 million dollars, with 2,180 known deaths. Conversely, without CrAg screening, the cost of treating meningitis was $3.09 million dollars with 3,806 deaths. Thus, despite the very low CrAg prevalence of 1.4% in the general HIV-infected population, and inadequate retention-in-care, CrAg screening averted 43% of deaths from cryptococcal meningitis at a cost of $662 per death averted. CONCLUSION: CrAg screening and treatment programs are cost-saving and lifesaving, assuming preemptive treatment is 77% effective in preventing death, and could be adopted and implemented by ministries of health to reduce mortality in those with advanced HIV disease. Even within HIV test-and-treat programs where CD4 testing is not performed, and CrAg prevalence is only 1.4%, CrAg screening is cost-effective.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Antígenos de Fungos/sangue , Análise Custo-Benefício , Cryptococcus/isolamento & purificação , Programas de Rastreamento/economia , Meningite Criptocócica/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/sangue , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adulto , Antifúngicos/administração & dosagem , Contagem de Linfócito CD4 , Cryptococcus/imunologia , Técnicas de Apoio para a Decisão , Hospitalização/economia , Humanos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Programas de Rastreamento/estatística & dados numéricos , Meningite Criptocócica/sangue , Meningite Criptocócica/mortalidade , Meningite Criptocócica/prevenção & controle , Modelos Econômicos , Guias de Prática Clínica como Assunto , Prevalência , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Resultado do Tratamento , Uganda/epidemiologia
9.
J Clin Microbiol ; 57(1)2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30257903

RESUMO

Over the past ten years, standard diagnostics for cryptococcal meningitis in HIV-infected persons have evolved from culture to India ink to detection of cryptococcal antigen (CrAg), with the recent development and distribution of a point-of-care lateral flow assay. This assay is highly sensitive and specific in cerebrospinal fluid (CSF), but is also sensitive in the blood to detect CrAg prior to meningitis symptoms. CrAg screening of HIV-infected persons in the blood prior to development of fulminant meningitis and preemptive treatment for CrAg-positive persons are recommended by the World Health Organization and many national HIV guidelines. Thus, CrAg testing is occurring more widely, especially in resource-limited laboratory settings. CrAg titer predicts meningitis and death and could be used in the future to customize therapy according to burden of infection.


Assuntos
Antígenos de Fungos/sangue , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/prevenção & controle , Testes Imediatos , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antígenos de Fungos/líquido cefalorraquidiano , Infecções Assintomáticas , Técnicas Bacteriológicas , Cryptococcus/imunologia , Humanos , Programas de Rastreamento , Meningite Criptocócica/microbiologia , Meningite Criptocócica/mortalidade , Sensibilidade e Especificidade , Taxa de Sobrevida
10.
J Acquir Immune Defic Syndr ; 80(2): 182-189, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30399034

RESUMO

BACKGROUND: HIV-infected persons with cryptococcal antigenemia (CrAg) are at high risk for meningitis or death. We evaluated the effect of CrAg screening and preemptive fluconazole therapy, adjunctive to antiretroviral therapy (ART), on 6-month survival among persons with advanced HIV/AIDS. METHODS: We enrolled HIV-infected, ART-naive participants with <100 CD4 cells/µL, in a stepped-wedge, cluster-randomized trial from July 2012 to December 2014 at 17 Ugandan clinics. Clinics participated in a prospective observational phase, followed by an interventional phase with laboratory-based, reflexive CrAg screening of residual CD4 count plasma. Asymptomatic CrAg+ participants received preemptive fluconazole therapy. We assessed 6-month survival using Cox-regression, adjusting for nadir CD4, calendar time, and stepped-wedge steps. RESULTS: We included 1280 observational and 2108 interventional participants, of whom 9.3% (195/2108) were CrAg+. CD4-, time-, and stepped-wedge-adjusted analyses demonstrated no difference in survival in the observational vs the interventional arms (hazard ratio = 1.34; 95% confidence interval: 0.86 to 2.10; P = 0.20). Fewer participants initiated ART in the interventional (73%) versus the observational phase (82%, P < 0.001). When ART initiation was modeled as a time-dependent covariate or confounder, survival did not differ. However, 6-month mortality of participants with CrAg titers <1:160 and CrAg-negative patients did not differ. Patients with CrAg titers ≥1:160 had 2.6-fold higher 6-month mortality than patients with titers <1:160. CONCLUSIONS: We observed no overall survival benefit of the CrAg screen-and-treat intervention. However, preemptive antifungal therapy for asymptomatic cryptococcosis seemed to be effective in patients with CrAg titer <1:160. A more aggressive approach is required for persons with CrAg titer ≥1:160.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Antifúngicos/uso terapêutico , Quimioprevenção/métodos , Criptococose/diagnóstico , Fluconazol/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adulto , Antígenos de Fungos/sangue , Contagem de Linfócito CD4 , Análise por Conglomerados , Criptococose/imunologia , Criptococose/prevenção & controle , Feminino , Guias como Assunto , Infecções por HIV/imunologia , Infecções por HIV/microbiologia , Humanos , Masculino , Programas de Rastreamento
11.
J Acquir Immune Defic Syndr ; 80(4): 436-443, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30550488

RESUMO

BACKGROUND: Mycobacterium avium complex prophylaxis is recommended for patients with advanced HIV infection. With the decrease in incidence of disseminated Mycobacterium avium complex infection and the availability of antiretroviral therapy (ART), the benefits of macrolide prophylaxis were investigated. This study examined the impact of macrolide prophylaxis on AIDS-defining conditions and HIV-associated mortality in a cohort of HIV-infected patients on ART. METHODS: Patients from TREAT Asia HIV Observational Database (September 2015 data transfer) aged 18 years and older with a CD4 count <50 cells/mm at ART initiation were included. The effect of macrolide prophylaxis on HIV-associated mortality or AIDS-defining conditions (as a combined outcome) and HIV-associated mortality alone were evaluated using competing risk regression. Sensitivity analysis was conducted in patients with a CD4 <100 cells/mm at ART initiation. RESULTS: Of 1345 eligible patients, 10.6% received macrolide prophylaxis. The rate of the combined outcome was 7.35 [95% confidence interval (CI): 6.04 to 8.95] per 100 patient-years, whereas the rate of HIV-associated mortality was 3.14 (95% CI: 2.35 to 4.19) per 100 patient-years. Macrolide use was associated with a significantly decreased risk of HIV-associated mortality (hazard ratio 0.10, 95% CI: 0.01 to 0.80, P = 0.031) but not with the combined outcome (hazard ratio 0.86, 95% CI: 0.32 to 2.229, P = 0.764). Sensitivity analyses showed consistent results among patients with a CD4 <100 cells/mm at ART initiation. CONCLUSIONS: Macrolide prophylaxis is associated with improved survival among Asian HIV-infected patients with low CD4 cell counts and on ART. This study suggests the increased usage and coverage of macrolide prophylaxis among people living with HIV in Asia.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antibacterianos/uso terapêutico , Macrolídeos/uso terapêutico , Complexo Mycobacterium avium/efeitos dos fármacos , Infecção por Mycobacterium avium-intracellulare/prevenção & controle , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/patologia , Adulto , Antibioticoprofilaxia/métodos , Contagem de Linfócito CD4 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Adulto Jovem
12.
Afr J Prim Health Care Fam Med ; 10(1): e1-e7, 2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30198285

RESUMO

BACKGROUND:  HIV-associated cryptococcal meningitis (CCM) and related mortality may be prevented by the effective implementation of a screen-and-treat intervention. Aim: The aim of this study was to assess the effectiveness of the screen-and-treat intervention at a regional hospital in KwaZulu-Natal province, South Africa. Method: This was a descriptive study in which the records of patients seen in 2015 and 2016 with a CD4 count ≤ 100 cell/mm3 were retrieved from National Health Laboratory Service (NHLS) records and matched against patients admitted for HIV-associated CCM. Results: A total of 5.1% (190 out of 3702) patients with CD4 count ≤ 100 cell/mm3 were cryptococcal antigen positive (CrAg +ve), of whom 22.6% (43 out of 190) were admitted with CCM. Patients who were CrAg +ve had significantly lower CD4 counts (mean CD4 = 38.9 ± 28.5) when compared to CrAg -ve patients (mean CD4 = 49.9 ± 37.4) with p = 0.0001. Only 2.6% (5 out of 190) of patients were referred for a lumbar puncture (LP) as part of the screen-and-treat intervention, whilst 38 who were CrAg +ve self-presented with CCM. Eighty-eight patients were admitted for suspected CCM: eight because of the screen-and-treat-intervention (none of whom had meningitis based on cerebrospinal fluid results) and 80 of whom self-presented and had confirmed CCM. The overall mortality of patients admitted with CCM was 30% (24 out of 80). Conclusion: The current ad-hoc screen-and-treat intervention was ineffective in detecting patients at risk of developing CCM. Systems need to be put in place to ensure that all CrAg +ve patients have an LP to detect subclinical CCM to improve the outcome for those with HIV-associated CCM.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Meningite Criptocócica/prevenção & controle , Infecções Oportunistas Relacionadas com a AIDS/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Linfócito CD4 , Criança , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Auditoria Médica , Meningite Criptocócica/etiologia , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , África do Sul , Adulto Jovem
13.
Pharmacol Res Perspect ; 6(4): e00423, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30073087

RESUMO

WHO information note indicates that isoniazid preventive therapy (IPT) is generally safe with little risk of hepatotoxicity. However, when the policy of IPT for HIV patients was introduced in Eritrea, frequent IPT-associated hepatotoxicity and fatality have been reported to the Pharmacovigilance Centre. The aim of the study is to assess the causal association of IPT and hepatotoxicity and identify possible risk factors in patients on Highly Active Anti-retroviral Therapy (HAART). This is a case series assessment of spontaneously reported cases to the Eritrean Pharmacovigilance Centre. Data extracted from VigiFlow (reported between 2014 and 2016) were exported to excel spread sheet for descriptive and qualitative analysis. Naranjo probability scale and Austin Bradford-Hill criteria were used to assess causality. The P-Method was used to assess preventability. A total of 31 of cases of hepatotoxicity related to IPT were retrieved. Majority (80.6%) of the cases were marked as "serious" due to life-threatening situation (n = 15), hospitalization (n = 6), and death (n = 4). Baseline liver function test was normal in 61.3% and hepatitis B and C infections were ruled out in 77.4%. IPT was discontinued in 26 cases and reaction abated in 22 of them. Causality assessment using Austin Bradford-Hill criteria found that the association was strong, consistent and specific with a plausible temporal relationship and biological mechanism. IPT-associated hepatotoxicity that led to treatment interruption and death was observed in patients on HAART in Eritrea. Hence, close laboratory monitoring of patients is recommended to minimize the risk.


Assuntos
Terapia Antirretroviral de Alta Atividade , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Infecções por HIV/tratamento farmacológico , Isoniazida/efeitos adversos , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adulto , Idoso , Eritreia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tuberculose/prevenção & controle
14.
Cochrane Database Syst Rev ; 8: CD004773, 2018 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-30156270

RESUMO

BACKGROUND: Cryptococcal disease remains one of the main causes of death in HIV-positive people who have low cluster of differentiation 4 (CD4) cell counts. Currently, the World Health Organization (WHO) recommends screening HIV-positive people with low CD4 counts for cryptococcal antigenaemia (CrAg), and treating those who are CrAg-positive. This Cochrane Review examined the effects of an approach where those with low CD4 counts received regular prophylactic antifungals, such as fluconazole. OBJECTIVES: To assess the efficacy and safety of antifungal drugs for the primary prevention of cryptococcal disease in adults and children who are HIV-positive. SEARCH METHODS: We searched the CENTRAL, MEDLINE PubMed, Embase OVID, CINAHL EBSCOHost, WHO International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, conference proceedings for the International AIDS Society (IAS) and Conference on Retroviruses and Opportunistic Infections (CROI), and reference lists of relevant articles up to 31 August 2017. SELECTION CRITERIA: Randomized controlled trials of adults and children, who are HIV-positive with low CD4 counts, without a current or prior diagnosis of cryptococcal disease that compared any antifungal drug taken as primary prophylaxis to placebo or standard care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and risk of bias, and extracted and analysed data. The primary outcome was all-cause mortality. We summarized all outcomes using risk ratios (RR) with 95% confidence intervals (CI). Where appropriate, we pooled data in meta-analyses. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: Nine trials, enrolling 5426 participants, met the inclusion criteria of this review. Six trials administered fluconazole, while three trials administered itraconazole.Antifungal prophylaxis may make little or no difference to all-cause mortality (RR 1.07, 95% CI 0.80 to 1.43; 6 trials, 3220 participants; low-certainty evidence). For cryptococcal specific outcomes, prophylaxis probably reduces the risk of developing cryptococcal disease (RR 0.29, 95% CI 0.17 to 0.49; 7 trials, 5000 participants; moderate-certainty evidence), and probably reduces deaths due to cryptococcal disease (RR 0.29, 95% CI 0.11 to 0.72; 5 trials, 3813 participants; moderate-certainty evidence). Fluconazole prophylaxis may make no clear difference to the risk of developing clinically resistant Candida disease (RR 0.93, 95% CI 0.56 to 1.56; 3 trials, 1198 participants; low-certainty evidence); however, there may be an increased detection of fluconazole-resistant Candida isolates from surveillance cultures (RR 1.25, 95% CI 1.00 to 1.55; 3 trials, 539 participants; low-certainty evidence). Antifungal prophylaxis was generally well-tolerated with probably no clear difference in the risk of discontinuation of antifungal prophylaxis compared with placebo (RR 1.01, 95% CI 0.91 to 1.13; 4 trials, 2317 participants; moderate-certainty evidence). Antifungal prophylaxis may also make no difference to the risk of having any adverse event (RR 1.07, 95% CI 0.88 to 1.30; 4 trials, 2317 participants; low-certainty evidence), or a serious adverse event (RR 1.08, 95% CI 0.83 to 1.41; 4 trials, 888 participants; low-certainty evidence) when compared to placebo or standard care. AUTHORS' CONCLUSIONS: Antifungal prophylaxis reduced the risk of developing and dying from cryptococcal disease. Therefore, where CrAG screening is not available, antifungal prophylaxis may be used in patients with low CD4 counts at diagnosis and who are at risk of developing cryptococcal disease.


Assuntos
Antifúngicos/uso terapêutico , Criptococose/prevenção & controle , Fluconazol/uso terapêutico , Soropositividade para HIV/complicações , Itraconazol/uso terapêutico , Prevenção Primária , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adulto , Antifúngicos/efeitos adversos , Contagem de Linfócito CD4 , Candida/efeitos dos fármacos , Causas de Morte , Criança , Criptococose/mortalidade , Farmacorresistência Fúngica , Fluconazol/efeitos adversos , Soropositividade para HIV/imunologia , Humanos , Itraconazol/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Expert Rev Anti Infect Ther ; 16(7): 579-588, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29976111

RESUMO

INTRODUCTION: Despite active antiretroviral therapy (ART), community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients and incurs high health costs. Areas covered: This article reviews the most recent publications on bacterial CAP in the HIV-infected population, focusing on epidemiology, prognostic factors, microbial etiology, therapy, and prevention. The data discussed here were mainly obtained from a non-systematic review using Medline, and references from relevant articles. Expert commentary: HIV-infected patients are more susceptible to bacterial CAP. Although ART improves their immune response and has reduced CAP incidence, these patients continue to present increased risk of pneumonia in part because they show altered immunity and because immune activation persists. The risk of CAP in HIV-infected patients and the probability of polymicrobial or atypical infections are inversely associated with the CD4 cell count. Mortality in HIV-infected patients with CAP ranges from 6% to 15% but in well-controlled HIV-infected patients on ART the mortality is low and similar to that seen in HIV-negative individuals. Vaccination and smoking cessation are the two most important preventive strategies for bacterial CAP in well-controlled HIV-infected patients on ART.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Pneumonia Bacteriana/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/etiologia , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adulto , Animais , Fármacos Anti-HIV/administração & dosagem , Contagem de Linfócito CD4 , Infecções Comunitárias Adquiridas/etiologia , Infecções Comunitárias Adquiridas/prevenção & controle , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Incidência , Pneumonia Bacteriana/etiologia , Pneumonia Bacteriana/prevenção & controle , Fatores de Risco , Abandono do Hábito de Fumar/métodos , Vacinação/métodos
16.
Int J STD AIDS ; 29(12): 1190-1193, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29945537

RESUMO

An increased risk of vaccine-preventable infections (VPIs) is seen in people living with HIV (PLWH), and current vaccine coverage and immunity is variable. Vaccine passports have the potential to improve vaccine coverage. The objective was to assess how successful a vaccine passport was in improving vaccine coverage in PLWH. Baseline immunity to VPIs was established in PLWH attending a single HIV clinic and vaccinations required were determined based on the BHIVA Vaccination Guidelines (2015). The passport was completed and the PLWH informed about additional vaccines they should obtain from primary care. After 6-9 months the passport was reviewed including confirmation if vaccines were given. PLWH satisfaction with the system was evaluated by a survey. Seventy-three PLWH provided sufficient data for analysis. At baseline significant proportions of PLWH were not immune/unvaccinated to the main VPIs, especially human papillomavirus, pneumococcus and measles. After the passport was applied immunity improved significantly (56% overall, p < 0.01) for most VPIs; however, full coverage was not achieved. The system was popular with PLWH. The passport was successful in increasing vaccination coverage although full or near-full coverage was not achieved. A more successful service would probably be achieved by commissioning English HIV clinics to provide all vaccines.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Infecções por HIV/diagnóstico , Avaliação de Programas e Projetos de Saúde/métodos , Vacinação/estatística & dados numéricos , Vacinas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepatite/prevenção & controle , Humanos , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Papillomaviridae , Pneumonia/prevenção & controle
18.
Vaccine ; 36(19): 2504-2506, 2018 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-29636247

RESUMO

Vaccination has been associated with a transient increase in viremia in HIV-infected individuals, although contradicting evidence persist in the literature. As part of a randomized placebo-controlled efficacy trial of the PCV7 in Malawi, we collected viral load and CD4+ T-cell counts from 237 adults who received two doses of vaccine or placebo, administered 4 weeks apart. Analyses were conducted separately for cART and non-cART users. Our analysis show no difference in viral loads between vaccine and placebo groups, regardless of cART use. Viremia decreased from 4.1 to 2.9 log10 copies/mL (p < 0.0001) among those using cART, consistent vaccine and placebo groups, but no changes were seen among the non-cART cohort. CD4+ T-cell counts remained unchanged regardless of cART use, or allocation to vaccine or placebo. We concluded that there was no evidence of detrimental effects of PCV7 administration on viral load or CD4+ T-cell counts six months after vaccination with PCV7.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Infecções por HIV/imunologia , Infecções por HIV/virologia , Vacina Pneumocócica Conjugada Heptavalente/uso terapêutico , Pneumonia Pneumocócica/prevenção & controle , Adulto , Linfócitos T CD4-Positivos , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Malaui , Masculino , Placebos , Carga Viral
19.
PLoS One ; 13(3): e0193571, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29513719

RESUMO

INTRODUCTION: In response to revisions in global and national policy in 2011, six-month isoniazid preventive therapy (IPT) became freely available as a preventive measure for people living with HIV in the uMgungundlovu District of KwaZulu-Natal province, South Africa. Given a difference in uptake and completion by sex, we sought to explore the reasons why Zulu women were more likely to accept and complete IPT compared to men in an effort to inform future implementation. METHODS: Utilising a community-based participatory research approach and ethnographic methods, we undertook 17 individual and group interviews, and met regularly with grassroots community advisory teams in three Zulu communities located in uMgungundlovu District between March 2012-December 2016. FINDINGS & DISCUSSION: Three categories described women's willingness to initiate IPT: women are caregivers, women are obedient, and appearance is important. The findings suggest that the success of IPT implementation amongst clinic-utilising women of uMgungundlovu is related to the cultural gender norms of uMakoti, isiZulu for "the bride" or "the wife." We invoke the cultural concept of inhlonipho, meaning "to show respect," to discuss how the cultural values of uMakoti may conflict with biomedical expectations of adherence. Such conflict can result in misinterpretations by healthcare providers or patients, and lead some patients to fear the repercussions of asking questions or contemplating discontinuation with the provider, preferring instead to appear obedient. We propose a shift in emphasis from adherence-focussed strategies, characteristic of the current biomedical approach, to practices that promote patient agency in an effort to offer IPT more appropriately. IMPLICATIONS: Building on existing tools, namely the harm reduction model and the use of mini-ethnography, we provide guidance on how to support women to participate as agents in the decision to initiate or continue IPT, decisions which may also impact the health and choices of the family.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antituberculosos/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Isoniazida/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Tuberculose/prevenção & controle , Infecções Oportunistas Relacionadas com a AIDS/etnologia , Infecções Oportunistas Relacionadas com a AIDS/psicologia , Cultura , Feminino , Identidade de Gênero , Humanos , Entrevistas como Assunto , Masculino , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Fatores Sexuais , África do Sul , Tuberculose/etnologia , Tuberculose/psicologia
20.
Int J Infect Dis ; 69: 29-34, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29408573

RESUMO

OBJECTIVES: This observational study recorded the malaria and sickle cell disease (SCD) profile of people living with HIV/AIDS (PLHA) and determined whether prophylactic co-trimoxazole (CTX) and the haemoglobin S (Hb S) allele influenced malaria episodes. METHODS: Sickling status, malaria episodes, and HIV type, as well as other data, were extracted retrospectively from the clinical records of 1001 patients attending the antiretroviral therapy clinic at Ridge Regional Hospital in Accra, Ghana between 2010 and 2015. Finger-prick capillary blood of returning patients (n=501) was tested for the haemoglobin (Hb) level and malaria, after information on malaria prevention methods was obtained through the administration of a questionnaire. RESULTS: The use of insecticide-treated mosquito nets was low (22.8%). CTX prophylaxis showed no significant influence on the overall number of malaria episodes from 2010 to 2015; however, it did show a statistically significant relationship (p=0.026) with the time elapsed since the last malaria episode. Even though 19% of participants possessed Hb S, it had no influence on malaria episodes. CONCLUSIONS: Hb S did not influence malaria in PLHA. Further studies in Hb SS and Hb SC are needed, as there are suggestions of increased frequency and severity of malaria. The impact of CTX prophylaxis on this cohort will be insightful.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Anemia Falciforme/tratamento farmacológico , Antibioticoprofilaxia , Infecções por HIV/tratamento farmacológico , Malária/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adulto , Anemia Falciforme/epidemiologia , Anemia Falciforme/imunologia , Contagem de Linfócito CD4 , Feminino , Gana/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Humanos , Malária/epidemiologia , Malária/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
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