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1.
Viruses ; 16(8)2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39205307

ABSTRACT

The study aimed to analyze changes in the clinical and epidemiological aspects of HIV-associated cryptococcal meningitis (CM) patients and to identify factors influencing their prognosis. Clinical data of patients with HIV-associated CM treated in Shanghai, China between 2013 and 2023 were collected. This study included 279 cases, 2.89% of AIDS patients, showing a yearly decrease in CM prevalence among AIDS patients (p < 0.001). Overall mortality was 10.39% with rates declining from a 2013 peak of 15.38% to 0% in 2023 despite no significant temporal pattern (p = 0.265). Diagnosis took an average of 18 ± 1 days post-symptoms, and admission CD4 counts averaged 29.2 ± 2.5 cells/µL, hinting at a non-significant decline. Frequent symptoms included fever (62.4%), headache (61.6%), fatigue (44.1%), and appetite loss (39.8%), with younger patients more likely to initially show signs of meningeal irritation. Logistic regression analysis underscored the prognostic importance of cerebrospinal fluid (CSF) white blood cell (WBC) count and procalcitonin levels. Over the decade spanning from 2013 to 2023, the incidence and mortality rates of CM among AIDS patients exhibited a downward trend. The average duration from the onset of CM to confirmation of diagnosis remained prolonged. CSF WBC count and procalcitonin levels were associated with unfavorable outcomes.


Subject(s)
AIDS-Related Opportunistic Infections , HIV Infections , Meningitis, Cryptococcal , Humans , Meningitis, Cryptococcal/epidemiology , Meningitis, Cryptococcal/mortality , China/epidemiology , Female , Male , Adult , Middle Aged , HIV Infections/complications , HIV Infections/epidemiology , AIDS-Related Opportunistic Infections/epidemiology , AIDS-Related Opportunistic Infections/mortality , Prognosis , CD4 Lymphocyte Count , Prevalence , Incidence , Young Adult
2.
Front Cell Infect Microbiol ; 14: 1407807, 2024.
Article in English | MEDLINE | ID: mdl-39206044

ABSTRACT

Background: Cryptococcosis is an invasive infection that commonly affects immunosuppressed individuals, especially patients with HIV infection. Cryptococcal infection in HIV-infected patients should be considered a major health concern because it is associated with high morbidity and mortality rates. In this study, we aimed to evaluate the clinical characteristics and prognostic factors of cryptococcal infections in human immunodeficiency virus (HIV)-infected patients to facilitate effective clinical management and improve patient outcomes. Methods: We reviewed and analyzed the clinical data and relevant laboratory test results of HIV-infected patients with positive cryptococcal cultures and reserved strains between 2013 and 2023 from Beijing Youan Hospital affiliated to Capital Medical University. The clinical characteristics and laboratory test results of the patients were compared, and the correlation between parameters and the prognoses of the patients at different observation timepoints (3, 6, 9, and 12 months) was analyzed. Results: A total of 76 patients (70 males and six females; median age, 37 years) were included in this study. The results indicated that the later the initiation of antiretroviral therapy (ART) after the diagnosis of HIV infection (> 6 months), the higher the probability of death. Analysis of the correlation between the time of ART initiation and the timing of treatment for cryptococcal infections showed that the time of ART initiation was strongly related to survival at different timepoints. Initiation of ART time within 0-4 weeks, 4-6 weeks and more than 6weeks of starting treatment for Cryptococcus infection was associated with a lower mortality rate at 12-month, the 3-month, 6- and 9-month follow-up timepoint separately. Conclusions: Although cryptococcal infection in HIV-infected patients continues to be a challenging and intricate issue, ART is a key factor that affects its prognosis. The later ART is started, the worse the prognosis of the infection. The time of ART initiation and the timing of treatment for cryptococcal infections should be further refined and balanced based on different clinical courses. Thus, clinicians should pay closer attention to cryptococcal infections in patients with HIV infection and initiate ART based on the patient's clinical condition.


Subject(s)
Cryptococcosis , HIV Infections , Humans , Female , Male , Adult , HIV Infections/complications , Prognosis , Cryptococcosis/mortality , Cryptococcosis/drug therapy , Cryptococcosis/complications , Middle Aged , Retrospective Studies , Young Adult , AIDS-Related Opportunistic Infections/microbiology , AIDS-Related Opportunistic Infections/mortality , Antifungal Agents/therapeutic use , Cryptococcus/isolation & purification , Hospitals , China/epidemiology
3.
BMC Infect Dis ; 24(1): 649, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38943055

ABSTRACT

BACKGROUND: Nocardia species can affect both immunocompetent and immunocompromised people. METHOD: This retrospective study, from 2009 to 2022, aims to compare the survival analyses of pulmonary nocardiosis in AIDS and non-AIDS patients in northeastern Thailand. RESULTS: A total of 215 culture-confirmed cases of pulmonary nocardiosis: 97 with AIDS and 118 without AIDS. The median CD4 count of AIDS patients was 11 cells/µL (range: 1-198), and 33% had concurrent opportunistic infections. 63.6% of 118 non-AIDS patients received immunosuppressive medications, 28.8% had comorbidities, and 7.6% had no coexisting conditions. Disseminated nocardiosis and pleural effusion were more prevalent among AIDS patients, whereas non-AIDS patients revealed more shock and respiratory failure. One hundred-fifty patients underwent brain imaging; 15 (10%) had brain abscesses. Patients with pulmonary nocardiosis have overall 30-day and 1-year mortality rates of 38.5% (95% CI: 32.3%, 45.4%) and 52.1% (95% CI: 45.6%, 58.9%), respectively. The Cox survival analysis showed that AIDS patients with disseminated nocardiosis had a 7.93-fold (95% CI: 2.61-24.02, p < 0.001) increased risk of death within 30 days compared to non-AIDS patients when considering variables such as age, Charlson comorbidity index, concurrent opportunistic infections, duration of illness, shock, respiratory failure, multi-lobar pneumonia, lung abscesses, and combination antibiotic therapy. While AIDS and pulmonary nocardiosis had a tendency to die within 30 days (2.09 (95% CI, 0.74-5.87, p = 0.162)). CONCLUSION: AIDS with pulmonary nocardiosis, particularly disseminated disease, is a serious opportunistic infection. Early diagnosis and empiric treatment with a multidrug regimen may be the most appropriate approach in a resource-limited setting.


Subject(s)
Nocardia Infections , Humans , Nocardia Infections/drug therapy , Nocardia Infections/microbiology , Nocardia Infections/mortality , Nocardia Infections/complications , Male , Female , Retrospective Studies , Adult , Middle Aged , Thailand/epidemiology , AIDS-Related Opportunistic Infections/microbiology , AIDS-Related Opportunistic Infections/mortality , AIDS-Related Opportunistic Infections/drug therapy , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/mortality , Aged , Nocardia/isolation & purification , Anti-Bacterial Agents/therapeutic use , Young Adult , CD4 Lymphocyte Count , Immunocompromised Host
4.
Trials ; 25(1): 311, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720383

ABSTRACT

BACKGROUND: HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB. METHODS: This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events. DISCUSSION: Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986.


Subject(s)
HIV Infections , Hospitalization , Levofloxacin , Rifampin , Tuberculosis , Humans , Rifampin/therapeutic use , Rifampin/administration & dosage , HIV Infections/complications , HIV Infections/drug therapy , Tuberculosis/drug therapy , Tuberculosis/diagnosis , Tuberculosis/mortality , Levofloxacin/therapeutic use , Treatment Outcome , Clinical Trials, Phase III as Topic , Antitubercular Agents/therapeutic use , Antitubercular Agents/adverse effects , Equivalence Trials as Topic , Drug Therapy, Combination , Prednisone/therapeutic use , Prednisone/administration & dosage , Prednisone/adverse effects , AIDS-Related Opportunistic Infections/drug therapy , AIDS-Related Opportunistic Infections/mortality , AIDS-Related Opportunistic Infections/microbiology , AIDS-Related Opportunistic Infections/diagnosis , Time Factors
5.
Medicina (B Aires) ; 84(2): 256-260, 2024.
Article in Spanish | MEDLINE | ID: mdl-38683510

ABSTRACT

INTRODUCTION: Meningeal cryptococcosis (MC) is a frequent cause of meningoencephalitis in people living with HIV (PLHIV), leading to substantial morbidity (20-55%). Clinical characteristics, lethality and adverse prognostic factors in PLHIV with MC admitted to intensive care units (ICUs) are described. METHODS: A retrospective observational study. Period from 11/21/2006 to 05/24/2023. It involved 154 adult PLHIV diagnosed with MC and admitted to ICUs. Percentages and absolute values were compared by Chi-Square or Fisher's test and medians by Mann-Whitney test. The association with mortality was assessed by logistic regression. SPSS 23.0 software was used. A p-value <0.05 was considered significant. RESULTS: Patients who died and those who survived were comparable in age and sex (p>0.05). Univariate analysis showed that impaired functional and nutritional status, lack of previous highly active antiretroviral therapy, CD4 <100 cells, APACHE II ≥ 13 and a PLHIV prognostic score ≥ 8 points, requiring mechanical ventilation (MV), respiratory failure, renal failure, neurological dysfunction or sepsis could be associated (p<0.05) with mortality. Logistic regression established that impaired functional and nutritional status, a PLHIV prognostic score ≥ 8, need for MV and presence of sepsis would be independent variables associated with mortality. CONCLUSION: The results indicate that altered functional and nutritional status, a PLHIV prognostic score ≥ 8 points, requiring MV and suffering sepsis on admission to the ICU are more frequent in deceased patients, and they could therefore serve as independent variables to predict a higher risk of mortality.


Introducción: La criptococosis meníngea (CM) es una causa frecuente de meningoencefalitis en personas que viven con HIV (PVHIV) y produce una importante morbimortalidad (20-55%). Se describen las características clínicas, la letalidad y las variables de mal pronóstico en PVHIV con CM, en unidades de cuidados intensivos (UCI). Métodos: Estudio observacional y retrospectivo. Período 21/11/2006 a 24/05/2023. Población evaluada: 154 PVHIV adultos, admitidos en UCI con diagnóstico de CM. Los porcentajes y valores absolutos, fueron comparados mediante Chi-Cuadrado o test de Fisher y las medianas mediante test de Mann-Whitney. La asociación con mortalidad se evaluó por regresión logística. Se utilizó el programa SPSS 23.0. Un valor p<0.05 fue considerado significativo. Resultados: Los pacientes que fallecieron y los que sobrevivieron fueron comparables en edad y sexo (p>0.05). El análisis univariado, observó que un estado funcional y nutricional alterado, falta de tratamiento antirretroviral previo (TARV), CD4 <100 células/µl, APACHE II ≥ 13 y un score pronóstico de PVHIV ≥ 8 puntos, requerir ventilación mecánica (VM), sufrir insuficiencia respiratoria, renal, disfunción neurológica o sepsis, podrían estar asociados (p<0.05) con mortalidad. La regresión logística estableció que un estado funcional y nutricional alterado, un score pronóstico PVHIV ≥ 8, necesitar VM y sufrir sepsis serían variables independientes asociadas a mortalidad. Conclusión: Los resultados indican que el estado funcional y nutricional alterado, un score pronóstico PVHIV ≥ 8 puntos, requerir VM y sufrir sepsis al ingreso a UCI podrían servir como variables independientes para predecir un mayor riesgo de mortalidad.


Subject(s)
AIDS-Related Opportunistic Infections , Intensive Care Units , Meningitis, Cryptococcal , Humans , Male , Female , Retrospective Studies , Adult , Meningitis, Cryptococcal/mortality , Meningitis, Cryptococcal/complications , Middle Aged , AIDS-Related Opportunistic Infections/mortality , AIDS-Related Opportunistic Infections/complications , Intensive Care Units/statistics & numerical data , Prognosis , Risk Factors , HIV Infections/complications , HIV Infections/mortality
6.
PLoS One ; 19(3): e0297619, 2024.
Article in English | MEDLINE | ID: mdl-38526997

ABSTRACT

The epidemiology of Human Immunodeficiency Virus (HIV)-associated pneumocystosis (HAP) is poorly described on a worldwide scale. We searched related databases between January 2000 and December 2022 for studies reporting HAP. Meta-analysis was performed using StatsDirect (version 2.7.9) and STATA (version 17) according to the random-effects model for DerSimonian and Laird method and metan and metaprop commands, respectively. Twenty-nine studies with 38554 HIV-positive, 79893 HIV-negative, and 4044 HAP populations were included. The pooled prevalence of HAP was 35.4% (95% CI 23.8 to 47.9). In contrast, the pooled prevalence of PCP among HIV-negative patients was 10.16% (95% CI 2 to 25.3). HIV-positive patients are almost 12 times more susceptible to PCP than the HIV-negative population (OR: 11.710; 95% CI: 5.420 to 25.297). The mortality among HAP patients was 52% higher than non-PCP patients (OR 1.522; 95% CI 0.959 to 2.416). HIV-positive men had a 7% higher chance rate for PCP than women (OR 1.073; 95% CI 0.674 to 1.706). Prophylactic (OR: 6.191; 95% CI: 0.945 to 40.545) and antiretroviral therapy (OR 3.356; 95% CI 0.785 to 14.349) were used in HAP patients six and three times more than HIV-positive PCP-negatives, respectively. The control and management strategies should revise and updated by health policy-makers on a worldwide scale. Finally, for better management and understanding of the epidemiology and characteristics of this coinfection, designing further studies is recommended.


Subject(s)
HIV Infections , Humans , Prevalence , HIV Infections/complications , HIV Infections/epidemiology , HIV Infections/mortality , HIV Infections/drug therapy , Pneumonia, Pneumocystis/epidemiology , Pneumonia, Pneumocystis/mortality , Male , Female , AIDS-Related Opportunistic Infections/epidemiology , AIDS-Related Opportunistic Infections/mortality , Global Health
7.
Clin Infect Dis ; 79(2): 487-497, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-38306316

ABSTRACT

BACKGROUND: Human immunodeficiency virus (HIV)-related opportunistic infections (OIs) cause substantial morbidity and mortality among people with HIV (PWH). US hospitalization and in-hospital mortality rates associated with OIs have not been published using data from the past decade. METHODS: We analyzed the National Inpatient Sample for the years 2011 through 2018. We used sociodemographic, financial, and hospital-level variables and identified hospitalizations for PWH and OI diagnoses. Using survey-weighted methods, we estimated all OI-related US hospitalization rates and in-hospital mortality per 100 000 PWH and modeled associated factors using survey-based multivariable logistic regression techniques. RESULTS: From 2011 to 2018, there were an estimated 1 710 164 (95% confidence interval [CI], 1 659 566-1 760 762) hospital discharges for PWH with 154 430 (95% CI, 148 669-159 717 [9.2%]) associated with an OI, of which 9336 (95% CI, 8813-9857; 6.0%) resulted in in-hospital mortality. Variables associated with higher odds of OI-related hospitalizations (compared to without an OI) included younger age, male sex, non-White race/ethnicity, and being uninsured (all likelihood ratio [LR] P < .001). Higher OI-related mortality was associated with older age (LR P < .001), male sex (LR P = .001), Hispanic race/ethnicity (LR P < .001), and being uninsured (LR P = .009). The OI-related hospitalization rate fell from 2725.3 (95% CI, 2266.9-3183.7) per 100 000 PWH in 2011 to 1647.3 (95% CI, 1492.5-1802.1) in 2018 (P < .001), but the proportion of hospitalizations with mortality was stable (5.9% in 2011 and 2018). CONCLUSIONS: Our findings indicate an ongoing need for continued funding of HIV testing, health insurance for all PWH, OI screening initiatives, review of current prophylaxis guidelines, and recruitment of more HIV clinicians.


Subject(s)
AIDS-Related Opportunistic Infections , Hospital Mortality , Hospitalization , Humans , Male , United States/epidemiology , Female , Hospitalization/statistics & numerical data , Middle Aged , Adult , AIDS-Related Opportunistic Infections/mortality , AIDS-Related Opportunistic Infections/epidemiology , Young Adult , Adolescent , HIV Infections/mortality , HIV Infections/epidemiology , Aged , Risk Factors
8.
Clin Microbiol Infect ; 30(5): 592-600, 2024 May.
Article in English | MEDLINE | ID: mdl-38145865

ABSTRACT

BACKGROUND: Fungal infections are common in HIV-infected individuals and significantly contribute to mortality. However, a substantial number of cases are undiagnosed before death. OBJECTIVE: To determine the frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa. METHODS: We conducted a scoping review of autopsy studies conducted in Africa. DATA SOURCES: PubMed, Scopus, Web of Science, Embase, Google Scholar, and African Journal Online. STUDY ELIGIBILITY CRITERIA: The review encompasses studies published from inception to September 2023, and no language restrictions were imposed during the search process. We included studies that reported histopathological or microbiological evidence for the diagnosis of fungal infections and other pathogens. DATA SYNTHESIS: Data were summarized using descriptive statistics and no meta-analysis was performed. RESULTS: We examined 30 articles reporting studies conducted between 1991 and 2019, encompassing a total of 13 066 HIV-infected decedents across ten African countries. In five studies, the autopsy type was not specified. Among those studies with specified autopsy types, 20 involved complete diagnostic autopsies, whereas 5 were categorized as partial or minimally invasive autopsies. There were 2333 pathogens identified, with 946 (40.5%) being mycobacteria, 856 (36.7%) fungal, 231 (3.8%) viral, 208 (8.9%) parasitic, and 92 (3.9%) bacterial. Of the 856 fungal pathogens identified, 654 (28.0%) were Cryptococcus species, 167 (7.2%) Pneumocystis jirovecii, 16 (0.69%) Histoplasma species, 15 (0.64%) Aspergillus species, and 4 (0.17%) Candida species. Other major non-fungal pathogens identified were cytomegalovirus 172 (7.37%) and Toxoplasma gondii 173 (7.42%). CONCLUSIONS: Invasive fungal infections occur in over one-third of people who succumb to HIV in Africa. In addition to cryptococcosis and Pneumocystis jirovecii pneumonia, integrating other priority fungal pathogen detection and management strategies into the broader framework of HIV care in Africa is recommended. This involves increasing awareness regarding the impact of fungal infections in advanced HIV disease and strengthening diagnostic and treatment capacity.


Subject(s)
Autopsy , HIV Infections , Mycoses , Humans , Africa/epidemiology , HIV Infections/complications , Mycoses/epidemiology , Mycoses/microbiology , Mycoses/mortality , Fungi/isolation & purification , Fungi/classification , AIDS-Related Opportunistic Infections/microbiology , AIDS-Related Opportunistic Infections/mortality , AIDS-Related Opportunistic Infections/epidemiology
9.
10.
Rev. cient. Esc. Univ. Cienc. Salud ; 9(1): 16-27, ene.- jun. 2022. tab.
Article in Spanish | LILACS, BIMENA | ID: biblio-1551960

ABSTRACT

Antecedentes: Las infecciones oportunistas son la principal causa de morbilidad, discapaci- dad y mortalidad en pacientes con VIH, aumentando el número de hospitalizaciones y costos en la atención. Objetivo: Estimar la proporción de infecciones oportunistas e identificar los factores asociados a su aparición en pacientes con VIH atendidos en el Servicio de Atención Integral del Hospital Nacional Dr. Mario Catarino Rivas, San Pedro Sula, 2019-2020. Métodos: Estudio no experimental, analítico de casos (infección oportunista presente) y controles. Se evaluaron 40 casos y 120 controles, con un nivel de confianza de 95%, poder estadístico de 80%, con muestreo tipo aleatorio simple. Se utilizó la distribución de variables entre casos y controles para la obtención de Odds Ratio. Resultados: Las infecciones oportunistas incluyeron: 52.5% (21) tuberculosis, 15.0% (6) histoplasmosis, 12.5% (5) citomegalovirus, 10.0% (4) toxoplasmosis, 10.0% (4) candidiasis, 7.5% (3) criptococosis. El conteo de linfocitos T CD4 fue <200 cel/mm3 en 60.0% (24) de grupo casos y 10.8% (13) de grupo control. La carga viral ˃1000 copias/ml (OR 14.500 IC95% 6.109-34.415), el antecedente de abandono (OR 4.363 IC95% 1.928-9.872) y el no tomar tratamiento antirretroviral (OR 64.076 IC95% 8.063-509.165) se asociaron a infecciones oportunistas. La carga viral mayor de 1000 copias/mL predominó en el grupo de casos, y se encontró asociación de esta con la presencia de infecciones oportunistas con OR 14.500 (IC 95% 6.109-34.415, p=.0001). Conclusión: El no tomar ARV aumenta 64 veces más el riesgo de desarrollar infecciones oportunistas y el haber abandonado el tratamiento antirretroviral aumenta 4 veces más la probabilidad de desarrollar una infección oportunista. El tratamiento antirretroviral de gran actividad y el apego al mismo es la mejor estrategia para prevenir las infecciones oportunistas en pacientes infectados por el VIH...(AU)


Subject(s)
Humans , HIV , AIDS-Related Opportunistic Infections/mortality , Viral Load , Anti-Retroviral Agents/administration & dosage
11.
N Engl J Med ; 386(12): 1109-1120, 2022 03 24.
Article in English | MEDLINE | ID: mdl-35320642

ABSTRACT

BACKGROUND: Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. METHODS: In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. RESULTS: A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, -3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was -0.40 log10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and -0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%). CONCLUSIONS: Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687.).


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Amphotericin B/administration & dosage , Antifungal Agents/administration & dosage , Fluconazole/administration & dosage , Flucytosine/administration & dosage , Meningitis, Cryptococcal/drug therapy , AIDS-Related Opportunistic Infections/mortality , Administration, Oral , Africa South of the Sahara , Amphotericin B/adverse effects , Antifungal Agents/adverse effects , Drug Administration Schedule , Drug Therapy, Combination , Fluconazole/adverse effects , Flucytosine/adverse effects , HIV Infections/complications , Meningitis, Cryptococcal/mortality
12.
PLoS Negl Trop Dis ; 15(4): e0009286, 2021 04.
Article in English | MEDLINE | ID: mdl-33819269

ABSTRACT

BACKGROUND: Histoplasmosis is acquired by inhalation of spores of the dimorphic fungus Histoplasma spp. Although this pathogen is distributed worldwide, it is more prevalent in the Americas. However, the real burden of histoplasmosis remains undefined in many endemic regions. METHODOLOGY: We conducted a series of 61 autopsies to individuals who died in a hospital in the Brazilian Amazon focused on infectious diseases. We performed a detailed histological and microbiological evaluation with genetic characterization of Histoplasma strains with the aim to evaluate the contribution of histoplasmosis to morbidity and mortality. Additionally, we assessed the clinicopathological correlation. PRINCIPAL FINDINGS: Evidence of Histoplasma infection was detected in 21 patients (34%). Eight cases were disseminated infections, all of them occurred in HIV-positive patients. Six cases were localized histoplasmosis, limited to the lungs. In seven patients Histoplasma DNA was detected by PCR in patients with no histological lesions. Histoplasma infection was detected in 38% of HIV-positive patients and was a major contributor to death in 22% of them. Lungs, liver and spleen were affected in all cases of disseminated histoplasmosis. Phylogenetic analysis of the strains suggested a high diversity of Histoplasma species circulating in the Brazilian Amazon. Histoplasmosis was clinically missed in 75% of the disseminated infections. CONCLUSIONS: The high incidence of histoplasmosis, the low index of clinical suspicion, and the severity of the disseminated disease highlight the need of proactively implementing sensitive routine screening methods for this pathogen in endemic areas. Antifungal prophylaxis against Histoplasma should be encouraged in the severely immunocompromised HIV patients in these areas. In conclusion, substantial mortality is associated with disseminated histoplasmosis among HIV-positive patients in the Brazilian Amazon.


Subject(s)
AIDS-Related Opportunistic Infections/microbiology , Histoplasma/classification , Histoplasma/genetics , Histoplasmosis/microbiology , AIDS-Related Opportunistic Infections/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Autopsy , Brazil/epidemiology , Female , Histoplasmosis/mortality , Histoplasmosis/pathology , Humans , Male , Middle Aged , Phylogeny , Prevalence , Young Adult
13.
BMC Infect Dis ; 21(1): 390, 2021 Apr 27.
Article in English | MEDLINE | ID: mdl-33906638

ABSTRACT

BACKGROUND: Late-diagnosis of HIV is a major challenge for the control and prevention of AIDS in the world. The present study aimed to specify factors associated with the late diagnosis of HIV in Iran from 1987 to 2016. METHODS: In this retrospective cohort study, data for 4402 diagnosed HIV/AIDS patients were extracted from 158 behavioral disease counseling centers of 31 Iranian provinces. We defined late diagnosis as having a CD4 count less than 350 within 3 months after diagnosis. Multiple logistic regression analysis was used to determine the factors influencing late diagnosis. Moreover, we used multivariate Cox regression to assess the association of these factors with the patients' survival. RESULTS: In this study, the prevalence of late diagnosis among the patients was 58.2%. People aged 50 years and over (adjusted OR = 3.55), transmission through blood transfusion (adjusted OR = 2.89), co-infection with tuberculosis (adjusted OR = 2.06), and male gender (adjusted OR = 1.38) were the strongest predictors for late diagnosis of HIV. On the other hand, baseline CD4 (adjusted HR = 2.21), people aged 50 and over (adjusted HR = 1.81), male gender (adjusted HR = 1.76), being a widow (adjusted HR = 1.68), people with unknown transmission way (adjusted HR = 18.24), people who inject drugs (adjusted HR = 1.87), diagnosis at previous years (adjusted HR = 2.45) and co-infection with tuberculosis (adjusted OR = 1.77) significantly associated with the survival of patients. CONCLUSION: The prevalence of late diagnosis is high among Iranian HIV/AIDS. The risk factors of late diagnoses include being males and aged 50 years and over, transmission through blood transfusion, and co-infection with tuberculosis. Therefore, implementation of screening programs for early diagnosis of HIV these high risk groups is recommended to Iranian health providers and policymakers.


Subject(s)
AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/epidemiology , Delayed Diagnosis/adverse effects , HIV , Mycobacterium tuberculosis , Tuberculosis/epidemiology , AIDS-Related Opportunistic Infections/mortality , Adult , CD4 Lymphocyte Count , Comorbidity , Counseling , Female , Follow-Up Studies , Humans , Iran/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Analysis , Survival Rate , Young Adult
14.
J Med Virol ; 93(8): 4901-4907, 2021 08.
Article in English | MEDLINE | ID: mdl-33788289

ABSTRACT

The coexistence of pulmonary tuberculosis (PTB) and human immunodeficiency virus (HIV) infection leads to high morbidity and mortality in these populations. Although antiretroviral therapy (ART) has decreased TB incidence in HIV-infected patients, this coexistence still prevails in China. Patients with HIV-PTB admitted to Beijing You An Hospital from 2014 to 2018 were retrospectively enrolled, and information on demographics, clinical characteristics, and laboratory findings were extracted from medical records. Predictors of death, including age (adjusted hazard ratio [AHR]: 1.03; 95% confidence interval [CI]: 1.00-1.05), tobacco use (AHR: 2.76; 95% CI: 1.54-4.94), history of tuberculosis (AHR: 3.53; 95% CI: 1.82-6.85), not being on ART (AHR: 2.94; 95% CI: 1.31-6.63), extrapulmonary tuberculosis (AHR: 2.391; 95% CI: 1.37-4.18), sputum smear positivity (AHR: 2.84; 95% CI: 1.61-4.99), CD4+ T cell count ≤ 50 cells/µl (AHR: 3.45; 95% CI: 1.95-6.10), and initiating ART ≥ 8 weeks after the initiation of antituberculous therapy (odds ratio: 3.30; 95% CI: 1.09-10.04). By contrast, there were no deaths among the six patients who began ART within 8 weeks after the initiation of antituberculous therapy. Age, tobacco use, not being on ART, extrapulmonary tuberculosis, sputum smear positivity, and CD4+ T cell count ≤50 cells/µl predict those patients at high risk of death among HIV-infected patients with PTB, and the time of initiating ART after the initiation of antituberculous therapy is also important for prognosis.


Subject(s)
AIDS-Related Opportunistic Infections/mortality , Tuberculosis, Pulmonary/mortality , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/drug therapy , Adult , Anti-Retroviral Agents/therapeutic use , Antitubercular Agents/therapeutic use , China/epidemiology , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Time-to-Treatment , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy
15.
Bosn J Basic Med Sci ; 21(6): 746-751, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-33596402

ABSTRACT

Kaposi sarcoma is a rare disease and there is a gap in the literature about which chemotherapeutics should be applied, especially for the classical type. We aimed to present our institutional data on the demographic characteristics, treatment, and treatment efficacy in 16 Kaposi sarcoma (KS) patients treated with chemotherapy. We retrospectively analyzed the demographic and clinical characteristics, and the chemotherapeutic agents administered to the 16 KS patients diagnosed in our center and treated with chemotherapy, based on the medical records obtained. The median age, gender, type of KS, site of involvement, cytotoxic agents administered, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles of the patients were evaluated. The median age at disease onset was 61.07 years (range, 39.4-85.8 years). Among the patients, 1 had immunosuppression-related KS, 4 had AIDS-related KS, and 11 had classical KS. In the first-line cytotoxic therapy, 7 patients received pegylated-liposomal doxorubicin (PLD), 6 patients received paclitaxel, 2 patients received oral etoposide, and 1 patient received the adriamycin, bleomycin, and vincristine regimen. In the Kaplan-Meier analysis, the PFS was 39.9 months (95% CI, 7.7-72.0). In the first-line setting, a significant difference in terms of PFS was observed between the PLD- and paclitaxel-treated groups (not reached vs. 12.8 months, p = 0.033). The OS was 66.1 months (95% CI, 30.2-102.0). The ORR of the 16 patients was 43.8%, and their DCR was 81.3%. No grade 3 or 4 toxicity was observed. This retrospective study showed that PLD seems better than paclitaxel in terms of PFS and response rates and it has shown to have a good safety profile in KS patients.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Sarcoma, Kaposi/drug therapy , AIDS-Related Opportunistic Infections/mortality , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Doxorubicin/analogs & derivatives , Doxorubicin/therapeutic use , Female , Humans , Male , Middle Aged , Paclitaxel/therapeutic use , Polyethylene Glycols/therapeutic use , Retrospective Studies , Sarcoma, Kaposi/mortality , Survival Rate , Turkey/epidemiology
17.
Mycoses ; 64(2): 203-211, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33141968

ABSTRACT

BACKGROUND: Although the widespread use of modern antiretroviral therapy (ART) has reduced the incidence of talaromycosis in people living with HIV, mortality remains as high as 20% in this population, even after appropriate antifungal treatment. OBJECTIVES: The objective of our study was to develop a risk assessment system for HIV-infected patients with comorbid talaromycosis, in order to provide these patients with appropriate, effective and potentially life-saving interventions at an early stage of their illness. PATIENTS/METHODS: This was a multicentre, retrospective cohort study conducted in China. We built a predictive model based on data from 11 hospitals, and a validated model using the data of 1 hospital located in an endemic area. RESULTS: Forward stepwise multivariate statistical calculations indicated that age, aspartate aminotransferase/alanine transaminase ratio and albumin levels, and BUN levels were valid, independent predictors of the risk of death in HIV-infected patients with talaromycosis. Our developed and validated risk scoring system is effective for the identification of HIV-infected patients with talaromycosis at high risk of death at hospital admission (p < .001; AUC = 0.860). In our study, our risk prediction model provided functional and robust discrimination in the validation cohort (p < .001; AUC = 0.793). CONCLUSION: The prognostic scoring system for mortality assessment developed in the present study is an easy-to-use clinical tool designed to accurately assist clinicians in identifying high-risk patients with talaromycosis.


Subject(s)
AIDS-Related Opportunistic Infections/mortality , HIV Infections/mortality , Mycoses/drug therapy , Mycoses/mortality , AIDS-Related Opportunistic Infections/drug therapy , Adult , Aged , Antifungal Agents , China/epidemiology , Female , HIV Infections/drug therapy , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors
18.
Future Microbiol ; 15: 1645-1652, 2020 11.
Article in English | MEDLINE | ID: mdl-33251866

ABSTRACT

Aim: To evaluate the clinical data and quantitative cerebrospinal fluid for associations with the outcome of cryptococcal meningitis (CM) patients in the hospital. Patients & methods: We retrospectively analyzed a total of 139 CM patients comprising 108 without HIV and 31 with HIV admitted in a Jiang Xi hospital. Resµlts: We found that CM patients with the high fungal burden (≥10 yeasts/µl) (26.3%) had a worse prognosis than those with the low fungal burden (<10 yeasts/µl). (4.9%) (p = 0.0007 <0.05). Conclusion: In CM patients, a fungal burden of 10 yeasts/µl in the first cerebrospinal fluid test may be used as an indicator of patient prognosis, and we can personalize patients' treatment based on the fungal burden to improve prognosis.


Subject(s)
AIDS-Related Opportunistic Infections/cerebrospinal fluid , HIV Infections/complications , Meningitis, Cryptococcal/cerebrospinal fluid , AIDS-Related Opportunistic Infections/microbiology , AIDS-Related Opportunistic Infections/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Cerebrospinal Fluid/chemistry , Cerebrospinal Fluid/microbiology , Child , Child, Preschool , Cryptococcus neoformans/genetics , Cryptococcus neoformans/isolation & purification , Cryptococcus neoformans/physiology , Female , Humans , Male , Meningitis, Cryptococcal/etiology , Meningitis, Cryptococcal/microbiology , Meningitis, Cryptococcal/mortality , Microscopy , Middle Aged , Prognosis , Retrospective Studies , Young Adult
19.
PLoS Negl Trop Dis ; 14(11): e0008823, 2020 11.
Article in English | MEDLINE | ID: mdl-33253210

ABSTRACT

Globally, early initiation of antiretroviral therapy for HIV led to a reduction in the estimated mortality from cryptococcal meningitis (CCM) from 624,700 in 2009 to 181,100 in 2014. However, CCM remains one of the leading causes of mortality among HIV infected patients especially in sub-Saharan Africa where 75% of the deaths occur. Most of the studies evaluating mortality have reported short-term mortality (at or before 10 weeks of therapy). We determined mortality and associated factors among patients treated for CCM in the CryptoDex trial (ISRCTN59144167) in Uganda, and the effect of dexamethasone adjunctive therapy on mortality at two years. We conducted a retrospective cohort study between May 2017 and July 2017 to determine the long term survival (up to 2 years post-randomization) of all patients who had been enrolled into the CryptoDex trial in Uganda. The CryptoDex trial recruited between April 2013 and February 2015. We estimated mortality rates and determined factors affecting mortality at two years using Cox regression. The study followed up 211 participants, 127 (60.2%) of whom were male. Sixteen participants (7.58%) were diagnosed with HIV at the same admission when CCM was diagnosed. By two years following randomization 127 (60%) participants had died, a mortality rate of 67 deaths per 100 person-years. Mortality was associated with Glasgow coma score (GCS) below 15 (adjusted Hazard ratio (aHR) 1.77, 95% CI: 1.02-2.44), p = 0.040; weight (aHR 0.97, per 1 Kg increase; 95% CI: 0.94-0.99), p = 0.003; and presence of convulsions (aHR 2.31, 95% CI: 1.32-4.04), p = 0.004, while dexamethasone use and fungal burden had no effect. Long-term mortality in CCM patients remains high even among patients receiving recommended therapy. Strategies to improve long-term survival in CCM patients are urgently needed, especially targeting those with reduced GCS, low weight, and convulsions.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , AIDS-Related Opportunistic Infections/mortality , Antifungal Agents/therapeutic use , Dexamethasone/therapeutic use , Meningitis, Cryptococcal/drug therapy , Meningitis, Cryptococcal/mortality , Adult , Amphotericin B/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Body Weight , Cohort Studies , Coma , Female , Fluconazole/therapeutic use , Humans , Male , Retrospective Studies , Risk Factors , Seizures , Uganda
20.
Medicine (Baltimore) ; 99(39): e22415, 2020 Sep 25.
Article in English | MEDLINE | ID: mdl-32991474

ABSTRACT

Kaposi sarcoma (KS) is an AIDS-defining angioproliferative malignancy associated with high morbidity and mortality. Most KS patients in regions with high incidence such as sub-Saharan Africa present late with advanced stage disease. Admitted KS patients have high mortality rates. Factors associated with mortality of admitted KS patients are poorly defined.We conducted a retrospective file review to ascertain reasons for admission and identify factors associated with mortality of admitted HIV-associated (epidemic) KS patients in Zambia. Baseline study variables were collected, and patients were retrospectively followed from admission to time of discharge or death.Mortality rate for admitted epidemic KS patients was high at 20%. The most common reasons for admission included advanced KS disease, severe anemia, respiratory tract infections, and sepsis. The majority (48%) of admitted patients had advanced clinical stage with visceral involvement on admission. Clinical predictors of mortality on univariate analysis included visceral KS [odds ratio (OR) = 13.74; 95% confidence interval (95% CI) = 1.68-113; P = 0.02), fever (OR = 26; 95% CI = 4.85-139; P = .001), and sepsis (OR = 35.56; 95% CI = 6.05-209; P = .001). Baseline hemoglobin levels (5.6 vs 8.2 g/dL; P = .001) and baseline platelet counts (63 x 10^9/L vs 205 x 10^9/L; P = .01) were significantly lower in mortalities vs discharges. Baseline white cell counts were higher in mortalities vs discharges (13.78 x 10^9/L vs 5.58 x 10^9/L; P = .01), and HIV-1 viral loads at the time of admission were higher in mortalities vs discharges (47,607 vs 40 copies/µL; P = .02). However, only sepsis (or signs and symptoms of sepsis) were independently associated with mortality after controlling for confounders.In conclusion, common reasons for admission of epidemic KS patients include advanced disease, severe anemia, respiratory tract infections, and signs and symptoms of sepsis. Signs and symptoms of sepsis are independent predictors of mortality in these patients.


Subject(s)
AIDS-Related Opportunistic Infections/mortality , Sarcoma, Kaposi/mortality , Adult , Female , Humans , Male , Middle Aged , Patient Admission/statistics & numerical data , Retrospective Studies , Young Adult , Zambia/epidemiology
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