Frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa: a scoping review.

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.

Deadly mpox risk in people with untreated HIV comes into view.

Analysis of hundreds of patients suggests mpox is "a different disease" in immunocompromised patients.

Proporción de infecciones oportunistas y factores de riesgo asociados a su aparición en pacientes con VIH / Proportion of opportunistic infections and risk factors associated with its appearance in patients with HIV

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)

Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis.

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.).

Identifying risk factors for late HIV diagnosis and survival analysis of people living with HIV/AIDS in Iran (1987-2016).

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.

High prevalence and mortality due to Histoplasma capsulatum in the Brazilian Amazon: An autopsy study.

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.

Mortality predictors among patients with HIV-associated pulmonary tuberculosis in Northeast China: A retrospective cohort analysis.

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.

Efficacy of chemotherapeutics in classic and non-classic Kaposi sarcoma: A single-center retrospective real-world data.

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.

Multicentre derivation and validation of a prognostic scoring system for mortality assessment in HIV-infected patients with talaromycosis.

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.

Cerebrospinal fluid microscopy as an index for predicting the prognosis of cryptococcal meningitis patients with and without HIV.

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.

Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda.

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.

Admitted AIDS-associated Kaposi sarcoma patients: Indications for admission and predictors of mortality.

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.

Mortality rate among HIV-positive children on ART in Northwest Ethiopia: a historical cohort study.

BACKGROUND: Though highly active antiretroviral therapy (HAART) has been available for more than a decade in Ethiopia, information regarding mortality rates of human immunodeficiency virus (HIV)-positive children after antiretroviral therapy antiretroviral therapy (ART) initiation is very scarce. Thus, this study intends to determine the predictors of mortality among HIV-positive children receiving ART in Amhara Region. METHODS: A multicenter facility-based historical cohort study was conducted in 538 HIV-positive children on ART from January 2012 to February 2017. We employed a standardized data extraction tool, adapted from ART entry and follow-up forms. Descriptive analyses were summarized using the Kaplan-Meier survival curve and log rank test. Then, the Cox-proportional hazard regression model was employed to estimate the hazard of death up to five-years after ART initiation. Variables with p-values ≤0.25 in bivariable analysis were candidates to the multivariable analysis. Finally, variables with p-values < 0.05 were considered as significant variables. RESULTS: The cohort contributed a total follow-up time of 14,600 child-months, with an overall mortality rate of 3.2 (95% CI: 2.3, 4.3) per 100 child-years. This study also indicated that HIV-infected children presenting with opportunistic infections (OIs) (AHR: 2.5, 95% CI: 1.04, 5.9), anemia (AHR: 3.1, 95% CI: 1.4, 6.7), severe immunodeficiency (AHR: 4.4, 95% CI: 1.7, 11.7), severe stunting (AHR: 3.3, 95% CI: 1.4, 8.0), severe wasting (AHR: 3.1, 95% CI: 1.3, 7.3), and advanced disease staging (III and IV) (AHR: 3.0, 95% CI: 1.2, 7.1) were at higher risk of mortality. CONCLUSION: A higher rate of mortality was observed in our study as compared to previous Ethiopian studies. HIV-positive children presenting with anemia, OIs, severe immunodeficiency, advanced disease staging (III and IV), severe stunting, and severe wasting were at higher risk of mortality.

Changes in D-dimer after initiation of antiretroviral therapy in adults living with HIV in Kenya.

BACKGROUND: Increased coagulation biomarkers are associated with poor outcomes among people living with HIV (PLHIV). There are few data available from African cohorts demonstrating the effect of antiretroviral therapy (ART) on coagulation biomarkers. METHODS: From March 2014 to October 2014, ART-naïve PLHIV initiating non-nucleoside reverse transcriptase inhibitor-based ART were recruited from seven clinics in western Kenya and followed for up to 12 months. Demographics, clinical history and blood specimens were collected. Logistic regression models adjusted for intrasite clustering examined associations between HIV viral load and D-Dimer at baseline. Mixed linear effects models were used to estimate mean change from baseline to 6 months overall, and by baseline viral load, sex and TB status at enrollment. Mean change in D-dimer at 6 months is reported on the log10 scale and as percentage change from baseline. RESULTS: Among 611 PLHIV enrolled, 66% were female, median age was 34 years (interquartile range (IQR) 29-43 years), 31 (5%) participants had tuberculosis and median viral load was 113,500 copies/mL (IQR: 23,600-399,000). At baseline, 311 (50.9%) PLHIV had elevated D-dimer (> 500 ng/mL) and median D-dimer was 516.4 ng/mL (IQR: 302.7-926.6) (log baseline D-dimer: 2.7, IQR: 2.5-3.0). Higher baseline D-dimer was significantly associated with higher viral load (p < 0.0001), female sex (p = 0.02) and tuberculosis (p = 0.02). After 6 months on ART, 518 (84.8%) PLHIV had achieved viral load < 1000 copies/mL and median D-dimer was 390.0 (IQR: 236.6-656.9) (log D-dimer: 2.6, IQR: 2.4-2.8). Mean change in log D-dimer from baseline to 6 months was - 0.12 (95%CI -0.15, - 0.09) (p < 0.0001) indicating at 31.3% decline (95%CI -40.0, - 23.0) in D-dimer levels over the first 6 months on ART. D-dimer decline after ART initiation was significantly greater among PLHIV with tuberculosis at treatment initiation (- 172.1, 95%CI -259.0, - 106.3; p < 0.0001) and those with log viral load > 6.0 copies/mL (- 91.1, 95%CI -136.7, - 54.2; p < 0.01). CONCLUSIONS: In this large Kenyan cohort of PLHIV, women, those with tuberculosis and higher viral load had elevated baseline D-dimer. ART initiation and viral load suppression among ART-naïve PLHIV in Kenya were associated with significant decrease in D-dimer at 6 months in this large African cohort.

HIV patients dying on anti-tuberculosis treatment: are undiagnosed infections still a problem in French Guiana?

OBJECTIVE: Despite scaling-up testing and antiretroviral treatment in Latin America, advanced HIV remains a significant public health problem. The objective of the present study was look for historical risk factors for death in French Guiana's HIV cohort taking into account the immunological status, the main opportunistic infections, and their treatment. A retrospective cohort study was conducted on data collected between 1992 and 2008 to identify factors associated with death in a cohort 2323 patients. RESULTS: There were 370 deaths for a total 9608 patient-years. Being on tuberculosis treatment was associated with a greater hazard of death. The diagnosis of confirmed tuberculosis, of histoplasmosis, of toxoplasmosis, and pneumocystosis were independently associated with death. Interactions terms between cotrimoxazole treatment and pneumocystosis, or between confirmed tuberculosis and tuberculosis treatment showed a protective treatment-effect. All patients having received anti-tuberculosis treatment (n = 347) did not have a final diagnosis of tuberculosis (n = 93). For histoplasmosis, 199 patients received antifungal treatment while 141 were diagnosed as having histoplasmosis. The number of patients on anti-tuberculosis drugs was far greater that the number of patients with confirmed tuberculosis, and these patients on treatment without confirmed tuberculosis had a twofold greater risk of dying.

Ventriculoperitoneal shunt insertion in human immunodeficiency virus infected adults: a systematic review and meta-analysis.

BACKGROUND: Hydrocephalus is a common, life threatening complication of human immunodeficiency virus (HIV)-related central nervous system opportunistic infection which can be treated by insertion of a ventriculoperitoneal shunt (VPS). In HIV-infected patients there is concern that VPS might be associated with unacceptably high mortality. To identify prognostic indicators, we aimed to compare survival and clinical outcome following VPS placement between all studied causes of hydrocephalus in HIV infected patients. METHODS: The following electronic databases were searched: The Cochrane Central Register of Controlled Trials, MEDLINE (PubMed), EMBASE, CINAHL Plus, LILACS, Research Registry, the metaRegister of Controlled Trials, ClinicalTrials.gov, African Journals Online, and the OpenGrey database. We included observational studies of HIV-infected patients treated with VPS which reported of survival or clinical outcome. Data was extracted using standardised proformas. Risk of bias was assessed using validated domain-based tools. RESULTS: Seven Hunderd twenty-three unique study records were screened. Nine observational studies were included. Three included a total of 75 patients with tuberculous meningitis (TBM) and six included a total of 49 patients with cryptococcal meningitis (CM). All of the CM and two of the TBM studies were of weak quality. One of the TBM studies was of moderate quality. One-month mortality ranged from 62.5-100% for CM and 33.3-61.9% for TBM. These pooled data were of low to very-low quality and was inadequate to support meta-analysis between aetiologies. Pooling of results from two studies with a total of 77 participants indicated that HIV-infected patients with TBM had higher risk of one-month mortality compared with HIV non-infected controls (odds ratio 3.03; 95% confidence-interval 1.13-8.12; p = 0.03). CONCLUSIONS: The evidence base is currently inadequate to inform prognostication in VPS insertion in HIV-infected patients. A population-based prospective cohort study is required to address this, in the first instance.

Causes of Hospitalization and Death among Newly Diagnosed HIV-Infected Adults in Thailand.

More than half of newly diagnosed HIV-infected patients enter to care with a low CD4 count. A retrospective cohort study was conducted among newly diagnosed HIV-infected adults who were hospitalized. Of 148 patients, median (interquartile range [IQR]) age was 39.3 (30.5-47.1) years and 114 (77%) patients were male. Baseline median (IQR) CD4 count was 79 (24-218) cells/mm3. The median (IQR) length of hospital stay was 8 (4-16) days. Half of the patients were hospitalized with AIDS-defining illness (ADI). Common opportunistic infections were Pneumocystis jirovecii pneumonia (20.3%) and tuberculosis (18.9%). CD4 count was statistically significantly associated with hospitalization with ADI (odds ratio: 0.85, per 10 cells/mm3 increased; 95% confidence interval: 0.80-0.90). The mortality was 5.4%. In conclusion, half of newly diagnosed Thai HIV-infected patients were hospitalized with ADI. Early detection of HIV infection leading to early antiretroviral therapy initiation and prevention of serious complications is essential.

Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: a three-arm, open-label, randomised, non-inferiority trial.

BACKGROUND: Optimal treatment regimens for AIDS-associated Kaposi sarcoma, a frequent contributor to morbidity and mortality among people with HIV, have not been systematically evaluated in low-income and middle-income countries, where the disease is most common. In this study, we aimed to investigate optimal treatment strategies for advanced stage disease in areas of high prevalence and limited resources. METHODS: In this open-label, non-inferiority trial, we enrolled people with HIV and advanced stage AIDS-associated Kaposi sarcoma attending 11 AIDS Clinical Trials Group sites in Brazil, Kenya, Malawi, South Africa, Uganda, and Zimbabwe. Eligible participants were randomly assigned (1:1:1) with a centralised computer system to receive either intravenous bleomycin and vincristine or oral etoposide (the investigational arms), or intravenous paclitaxel (the control arm), together with antiretroviral therapy (ART; combined efavirenz, tenofovir disoproxil fumarate, and emtricitabine). The primary outcome was progression-free survival (PFS) at week 48, using a 15% non-inferiority margin to compare the investigational groups against the active control group. Safety was assessed in all eligible treated study participants. The study was registered with ClinicalTrials.gov, NCT01435018. FINDINGS: 334 participants were enrolled between Oct 1, 2013, and March 8, 2018, when the study was closed early due to inferiority of the bleomycin and vincristine plus ART arm, as per the recommendations of the Data and Safety Monitoring Board (DSMB). The etoposide plus ART arm also closed due to inferiority in March, 2016, following a DSMB recommendation. Week-48 PFS rates were higher in the paclitaxel plus ART arm than in both investigational arms. The absolute differences in PFS were -30% (95% CI -52 to -8) for the comparison of paclitaxel plus ART (week 48 PFS 50%, 32 to 67; n=59) and etoposide plus ART (20%, 6 to 33; n=59), and -20% (-33% to -7%) for the comparison of paclitaxel plus ART (64%, 55 to 73; n=138) and bleomycin and vincristine plus ART (44%, 35 to 53; n=132). Both CIs overlapped the non-inferiority margin. The most common adverse events, in 329 eligible participants who began treatment, were neutropenia (48 [15%]), low serum albumin (33 [10%]), weight loss (29 [9%]), and anaemia (28 [9%]), occurring at similar frequency across treatment arms. INTERPRETATION: Non-inferiority of either investigational intervention was not shown, with paclitaxel plus ART showing superiority to both oral etoposide plus ART and bleomycin and vincristine plus ART, supporting its use in treating advanced AIDS-associated Kaposi sarcoma in resource-limited settings. FUNDING: US National Institute of Allergy and Infectious Diseases and National Cancer Institute, National Institutes of Health.

Histoplasmosis diseminada y síndrome hemofagocítico en pacientes VIH: serie de casos en un hospital peruano / Disseminated histoplasmosis and haemophagocytic syndrome in HIV patients: a case series in a Peruvian hospital

ANTECEDENTES: La histoplasmosis diseminada (HD) es una infección fúngica oportunista en pacientes con infección por VIH gravemente inmunocomprometidos. El síndrome hemofagocítico (SHF), que puede presentarse en estos pacientes coinfectados cuando la respuesta inmunitaria está significativamente alterada, suele estar asociado a una elevada mortalidad. OBJETIVOS: Describir las características epidemiológicas, clínicas, analíticas y microbiológicas, así como evaluar la presencia de SHF, en pacientes con HD-VIH. MÉTODOS: Estudio retrospectivo de serie de casos, consistente en la revisión de registros clínicos de pacientes con diagnóstico de HD e infección VIH, durante los años 2014 y 2015. RESULTADOS: El 1,3% (8/597) de los pacientes VIH presentaron HD. El 100% se hallaban en estadio C3 y el 75% (6/8) no se encontraban en terapia antirretroviral combinada (TARVc). Los dos pacientes restantes habían comenzado recientemente el tratamiento con TARVc (posible síndrome de reconstitución inmunológica). El 62,5% (5/8) cumplieron con criterios diagnósticos de SHF. Las manifestaciones clínicas más frecuentes fueron el síndrome linfoproliferativo y consuntivo, el compromiso respiratorio y la citopenia. En el 75% (6/8) de los pacientes se aisló Histoplasma en ganglios, en el 25% (2/8) en muestras hemáticas y en uno adicionalmente en tejido intestinal. La terapia antifúngica fue anfotericina B desoxicolato; no se emplearon adyuvantes. La mortalidad global fue del 50%. CONCLUSIONES: En nuestra serie la coinfección HD-VIH progresó en la mayoría de los casos a SHF con elevada mortalidad. El cuadro clínico puede asemejarse al de otras enfermedades sistémicas, como la tuberculosis, o presentarse simultáneamente a ellas. Con el fin de obtener un diagnóstico precoz y poder prescribir la terapia específica oportuna es importante poseer un adecuado índice de sospecha en pacientes con síndrome linfoproliferativo y consuntivo asociado a citopenia grave

BACKGROUND: Disseminated histoplasmosis (DH) is an opportunistic fungal infection in severely immunocompromised patients with HIV infection. Haemophagocytic syndrome (HFS), which can occur in these co-infected patients when the immune response is significantly altered, is often associated with high mortality. AIMS: To describe the epidemiological, clinical, analytical and microbiological characteristics, along with studying the presence of HFS, in patients with DH-HIV. METHODS: A retrospective study was conducted on a case series using data from the clinical records of patients diagnosed with DH and HIV infection during the years 2014 and 2015. RESULTS: DH was diagnosed in 8 (1.3%) of 597 HIV patients. All patients were in stage C3, and 75% (6/8) were not receiving combined antiretroviral therapy (CART). The remaining two patients had recently begun CART (possible immune reconstitution syndrome). Five (62.5%) of the 8 patients met criteria for HFS. The most frequent clinical symptoms were lymphoproliferative and consumptive syndrome, respiratory compromise, and cytopenia. Histoplasma was isolated in lymph nodes of 75% (6/8) of the patients, in blood samples in 25% (2/8), and also in intestinal tissue in one patient. The antifungal therapy was amphotericin B deoxycholate, without adjuvants. The overall mortality was 50%. CONCLUSIONS: In this case series, DH-HIV co-infection frequently progressed to HFS with high mortality. The clinical picture may resemble that of other systemic opportunistic infections, such as tuberculosis, or can take place simultaneously with other infections. Clinical suspicion is important in patients with severe cytopenia and lymphoproliferative and consumptive syndrome in order to establish an early diagnosis and prescribing a timely specific therapy