scholarly journals Seizures in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: Predictors and Outcomes

2019 ◽  
Vol 6 (11) ◽  
Author(s):  
Katelyn A Pastick ◽  
Ananta S Bangdiwala ◽  
Mahsa Abassi ◽  
Andrew G Flynn ◽  
Bozena M Morawski ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cerebrospinal Fluid ◽  
Cryptococcal Meningitis ◽  
Proportional Hazards ◽  
Neurocognitive Function ◽  
Cox Proportional Hazards ◽  
Neurocognitive Performance ◽  
Cox Proportional Hazards Models ◽  
Immunodeficiency Virus ◽  
Z Scores

Abstract Background Seizures commonly occur in patients with cryptococcal meningitis, yet risk factors and outcomes related to seizures are not well described. Methods We performed post hoc analyses on participants prospectively enrolled in 3 separate human immunodeficiency virus (HIV)-associated cryptococcal meningitis clinical trials during 2010–2017. Documentation of seizures at presentation or during hospitalization and antiseizure medication receipt identified participants with seizures. We summarized participant characteristics by seizure status via Kruskal-Wallis and χ 2 tests. Cox proportional hazards models analyzed the relationship between seizures and mortality. We compared mean quantitative neurocognitive performance Z (QNPZ-8) scores, and individual domain z-scores, at 3-months using independent t tests. Results Among 821 HIV-infected cryptococcal meningitis participants, 28% (231 of 821) experienced seizures: 15.5% (127 of 821) experienced seizures at presentation, and 12.7% (104 of 821) experienced incident seizures. Participants with seizures at presentation had a significantly lower Glasgow coma scale ([GCS] <15; P < .001), CD4 count (<50 cells/mcL; P = .02), and higher cerebrospinal fluid (CSF) opening pressure (>25 cm H2O; P = .004) when compared with participants who never experienced seizures. Cerebrospinal fluid fungal burden was higher among those with seizures at presentation (125 000 Cryptococcus colony-forming units [CFU]/mL CSF) and with seizures during follow-up (92 000 CFU/mL) compared with those who never experienced seizures (36 000 CFU/mL, P < .001). Seizures were associated with increased 10-week mortality (adjusted hazard ratio = 1.45; 95% confidence interval, 1.11–1.89). Participants with seizures had lower neurocognitive function at 3 months (QNPZ-8 = −1.87) compared with those without seizures (QNPZ-8 = −1.36; P < .001). Conclusions Seizures were common in this HIV-associated cryptococcal meningitis cohort and were associated with decreased survival and neurocognitive function.

scholarly journals A Single Quantifiable Viral Load Is Predictive of Virological Failure in Human Immunodeficiency Virus (HIV)-Infected Patients on Combination Antiretroviral Therapy: The Austrian HIV Cohort Study

2016 ◽  
Vol 3 (2) ◽  
Author(s):  
Gisela Leierer ◽  
Katharina Grabmeier-Pfistershammer ◽  
Andrea Steuer ◽  
Mario Sarcletti ◽  
Maria Geit ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Virological Failure ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Combination Antiretroviral Therapy ◽  
Limit Of Quantification ◽  
Cox Proportional Hazards Models ◽  
Increased Risk ◽  
Immunodeficiency Virus

Abstract Background.  Viral loads (VLs) detectable at low levels are not uncommon in patients on combination antiretroviral therapy (cART). We investigated whether a single quantifiable VL predicted virological failure (VF). Methods.  We analyzed patients receiving standard regimens with at least 1 VL measurement below the limit of quantification (BLQ) in their treatment history. The first VL measurement after 6 months of unmodified cART served as baseline VL for the subsequent analyses of the time to reach single VL levels of ≥200, ≥400, and ≥1000 copies/mL. Roche TaqMan 2.0 was used to quantify human immunodeficiency virus-1 ribonucleic acid. Factors associated with VF were determined by Cox proportional hazards models. Results.  Of 1614 patients included in the study, 68, 44, and 34 experienced VF ≥200, ≥400, and ≥1000 copies/mL, respectively. In multivariable analyses, compared with patients who were BLQ, a detectable VL ≤ 50 and VL 51–199 copies/mL predicted VF ≥ 200 copies/mL (hazards ratio [HR] = 2.19, 95% confidence interval [CI] = 1.06–4.55 and HR = 4.21, 95% CI = 2.15–8.22, respectively). In those with VL 51–199 copies/mL, a trend for an increased risk of VF ≥400 and VF ≥1000 copies/mL could be found (HR = 2.13, 95% CI = 0.84–5.39 and HR = 2.52, 95% CI = 0.96–6.60, respectively). Conclusions.  These findings support closer monitoring and adherence counseling for patients with a single measurement of quantifiable VL <200 copies/mL.

scholarly journals Cerebrospinal Fluid Culture Positivity and Clinical Outcomes After Amphotericin-Based Induction Therapy for Cryptococcal Meningitis

2015 ◽  
Vol 2 (4) ◽  
Author(s):  
Melissa A. Rolfes ◽  
Joshua Rhein ◽  
Charlotte Schutz ◽  
Kabanda Taseera ◽  
Henry W. Nabeta ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cerebrospinal Fluid ◽  
Clinical Outcomes ◽  
Antifungal Therapy ◽  
Induction Therapy ◽  
Cryptococcal Meningitis ◽  
Cox Regression ◽  
Culture Positivity ◽  
Immunodeficiency Virus ◽  
Cerebrospinal Fluid Culture

Abstract Background.  Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis. However, 40%–50% of individuals have positive cerebrospinal fluid (CSF) fungal cultures at completion of 2 weeks of amphotericin induction therapy. Residual CSF culture positivity has historically been associated with poor clinical outcomes. We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort. Methods.  Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Uganda and South Africa received amphotericin (0.7–1.0 mg/kg per day) plus fluconazole (800 mg/day) for 2 weeks, followed by “enhanced consolidation” therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile, and then 400 mg/day for 8 weeks. Participants were randomized to receive antiretroviral therapy (ART) either 1–2 or 5 weeks after diagnosis and observed for 6 months. Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures. Mortality, immune reconstitution inflammatory syndrome (IRIS), and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression. Results.  Of 132 participants surviving 2 weeks, 57% had sterile CSF at 2 weeks, 23 died within 5 weeks, and 40 died within 6 months. Culture positivity was not significantly associated with mortality (adjusted 6-month hazard ratio, 1.2; 95% confidence interval, 0.6–2.3; P = .28). Incidence of IRIS or relapse was also not significantly related to culture positivity. Conclusions.  Among patients, all treated with enhanced consolidation antifungal therapy and ART, residual cryptococcal culture positivity was not found to be associated with poor clinical outcomes.

scholarly journals Relationship of Human Immunodeficiency Virus Viral Load in Cerebrospinal Fluid and Plasma in Patients Co-infected With Cryptococcal Meningitis

2017 ◽  
Vol 4 (2) ◽  
Author(s):  
Christina C. Chang ◽  
Richard Kangethe ◽  
Saleha Omarjee ◽  
Keshni Hiramen ◽  
Bernadett Gosnell ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cerebrospinal Fluid ◽  
Cryptococcal Meningitis ◽  
Cd4 T Cell ◽  
Hiv Rna ◽  
Cell Percentage ◽  
Immunodeficiency Virus ◽  
A Prospective Study ◽  
Relationship Of ◽  
Inflammatory Syndrome

Abstract We measured human immunodeficiency virus (HIV) ribonucleic acid (RNA) in paired cerebrospinal fluid (CSF) and plasma samples in a prospective study of 91 HIV-infected, antiretroviral therapy-naive patients with cryptococcal meningitis. Cerebrospinal fluid HIV RNA was lower than in plasma (median 4.7 vs 5.2 log10 copies/mL, P < .0001) and positively correlated with plasma HIV RNA, peripheral CD4+ T-cell percentage, and CSF CXCL10. Plasma/CSF ratio of HIV RNA ranged widely from 0.2 to 265.5 with a median of 2.6. Cerebrospinal fluid quantitative cryptococcal culture positively correlated with CSF CCL2 and CCL3. CSF-plasma viral discordance was not associated with cryptococcal-associated immune reconstitution inflammatory syndrome.

scholarly journals Unique Cerebrospinal Fluid Profiles of Patients With Human Immunodeficiency Virus- Associated Cryptococcal Meningitis With a Ventriculoperitoneal Shunt : A Retrospective Cohort Study

2021 ◽  
Author(s):  
Ran Tao ◽  
Lijun Xu ◽  
Yongzheng Guo ◽  
Xiaoke Xu ◽  
Jiesheng Zheng ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cerebrospinal Fluid ◽  
Cohort Study ◽  
Cryptococcal Meningitis ◽  
Retrospective Cohort ◽  
Protein Levels ◽  
Ventriculoperitoneal Shunting ◽  
Immunodeficiency Virus ◽  
Cerebrospinal Fluid Protein

Abstract Background: The long-term complications of ventriculoperitoneal shunting in patients with human immunodeficiency virus-associated cryptococcal meningitis remain unclear. We conducted a case-control study investigating the long-term effects of ventriculoperitoneal shunting in patients with human immunodeficiency virus-associated cryptococcal meningitis. Methods: Between January 2011 and December 2019, 112 patients with human immunodeficiency virus-associated cryptococcal meningitis from our hospital were enrolled in this retrospective cohort study. Of those, 30 (26.8%) patients underwent ventriculoperitoneal shunting (VPS group); the remaining (n = 82; 73.2%) were included in the non-VPS group. Survival was estimated using the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were performed to identify factors associated with ventriculoperitoneal shunting. Results: The VPS group (n=21) had lower cerebrospinal fluid glucose (2.51±0.81 vs. 3.16±0.48 mmol/L; P=0.002) and higher cerebrospinal fluid protein levels (1.37 [0.83–1.49] vs. 0.49 [0.49–0.49] g/L; P=0.011) than did the non-VPS group (n=21). Intracranial pressure decreased from 400 (375–450) to 164 (145–172) mmH2O in the VPS group (log-rank, P<0.001). The 24-week cumulative survival rates in the VPS and non-VPS groups were 100.0% and 79.8%, respectively (P=0.035). The misdiagnosis rates of tuberculous meningitis were 28.6% and 0.0%, respectively (P=0.008). Conclusions: Ventriculoperitoneal shunting decreased the intracranial pressure and 24-week mortality in patients with human immunodeficiency virus-associated cryptococcal meningitis, but significantly increased cerebrospinal fluid protein levels, leading to a higher misdiagnosis rate of tuberculous meningitis. Physicians should be aware of these changes in the cerebrospinal fluid profiles of patients with human immunodeficiency virus-associated cryptococcal meningitis with a ventriculoperitoneal shunt.

scholarly journals Deaths Attributable to Cancer in the US Human Immunodeficiency Virus Population During 2001–2015

2020 ◽  
Author(s):  
Marie-Josèphe Horner ◽  
Meredith S Shiels ◽  
Ruth M Pfeiffer ◽  
Eric A Engels
Keyword(s):  
Human Immunodeficiency Virus ◽  
Proportional Hazards ◽  
Kaposi Sarcoma ◽  
Cancer Registries ◽  
The United States ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Attributable Mortality ◽  
Immunodeficiency Virus ◽  
The Us

Abstract Background Antiretroviral therapy (ART) has reduced mortality among people living with human immunodeficiency virus (HIV), but cancer remains an important cause of death. We characterized cancer-attributable mortality in the HIV population during 2001–2015. Methods We used data from population-based HIV and cancer registries in the United States (US). Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) associating cancer diagnoses with overall mortality, we could perhaps cut these words to accommodate the word limit. However readers will probably want to know what statistical adjustments were made to the model. Population-attributable fractions (PAFs) were calculated using these HRs and the proportion of deaths preceded by cancer. Cancer-specific PAFs and cancer-attributable mortality rates were calculated for demographic subgroups, AIDS-defining cancers (Kaposi sarcoma [KS], non-Hodgkin lymphoma [NHL], cervical cancer), and non–AIDS-defining cancers. Results Cancer-attributable mortality was 386.9 per 100 000 person-years, with 9.2% and 5.0% of deaths attributed to non–AIDS-defining and AIDS-defining cancers, respectively. Leading cancer-attributable deaths were from NHL (3.5%), lung cancer (2.4%), KS (1.3%), liver cancer (1.1%), and anal cancer (0.6%). Overall, cancer-attributable mortality declined from 484.0 per 100 000 person-years during 2001–2005 to 313.6 per 100 000 person-years during 2011–2015, while the PAF increased from 12.6% to 17.1%; the PAF for non–AIDS-defining cancers increased from 7.2% to 11.8% during 2011–2015. Cancer-attributable mortality was highest among those aged ≥60 years (952.2 per 100 000 person-years), with 19.0% of deaths attributed to non–AIDS-defining cancers. Conclusions Although cancer-attributable mortality has declined over time, it remains high and represents a growing fraction of deaths in the US HIV population. Mortality from non–AIDS-defining cancers may rise as the HIV population ages. ART access, early cancer detection, and improved cancer treatment are priorities for reducing cancer-attributable mortality.

scholarly journals Persistence With Human Immunodeficiency Virus Pre-exposure Prophylaxis in the United States, 2012–2017

2020 ◽  
Author(s):  
Ya-Lin A Huang ◽  
Guoyu Tao ◽  
Dawn K Smith ◽  
Karen W Hoover
Keyword(s):  
Human Immunodeficiency Virus ◽  
Proportional Hazards ◽  
Patient Characteristics ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Research Database ◽  
Female Sex ◽  
Younger Age ◽  
Immunodeficiency Virus ◽  
Exposure Prophylaxis

Abstract Background Daily oral pre-exposure prophylaxis (PrEP) is highly effective in preventing human immunodeficiency virus (HIV) infection if used adherently throughout periods of HIV risk. We estimated PrEP persistence among cohorts of persons with commercial or Medicaid insurance. Methods We analyzed data from the IBM MarketScan Research Database to identify persons aged 18–64 years who initiated PrEP between 2012 and 2017. We assessed PrEP persistence by calculating the time period that each person continued filling PrEP prescriptions until there was a gap in prescription fills &gt; 30 days. We used Kaplan-Meier time-to-event methods to estimate the proportion of PrEP users who persisted with PrEP at 3, 6, and 12 months after initiation, and constructed Cox proportional hazards models to determine patient characteristics associated with nonpersistence. Results We studied 11 807 commercially insured and 647 Medicaid insured persons with PrEP prescriptions. Commercially insured patients persisted for a median time of 13.7 months (95% confidence interval [CI], 13.3–14.1), compared to 6.8 months (95% CI, 6.1–7.6) among Medicaid patients. Additionally, female sex, younger age, residence in rural location, and black race were associated with shorter persistence. After adjusting for covariates, we found that female sex (hazard ratio [HR], 1.81 [95% CI, 1.56–2.11]) and younger age (18–24 years: HR, 2.38 [95% CI, 2.11–2.69]) predicted nonpersistence. Conclusions More than half of commercially insured persons who initiated PrEP persisted with it for 12 months, compared to a third of those with Medicaid. A better understanding of reasons for nonpersistence is important to support persistent PrEP use and to develop interventions designed for the diverse needs of at-risk populations.

scholarly journals Hepatotoxicity and Liver-Related Mortality in Women of Childbearing Potential Living With Human Immunodeficiency Virus and High CD4 Cell Counts Initiating Efavirenz-Containing Regimens

2020 ◽  
Author(s):  
Debika Bhattacharya ◽  
Amita Gupta ◽  
Camlin Tierney ◽  
Sharon Huang ◽  
Marion G Peters ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Women Of Childbearing Age ◽  
Childbearing Age ◽  
Severe Hepatotoxicity ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Related Mortality

Abstract Background Severe hepatotoxicity in people with human immunodeficiency virus (HIV) receiving efavirenz (EFV) has been reported. We assessed the incidence and risk factors of hepatotoxicity in women of childbearing age initiating EFV-containing regimens. Methods In the Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, ART-naive pregnant women with HIV and CD4 count ≥ 350 cells/μL and alanine aminotransferase ≤ 2.5 the upper limit of normal were randomized during the antepartum and postpartum periods to antiretroviral therapy (ART) strategies to assess HIV vertical transmission, safety, and maternal disease progression. Hepatotoxicity was defined per the Division of AIDS Toxicity Tables. Cox proportional hazards models were constructed with covariates including participant characteristics, ART regimens, and timing of EFV initiation. Results Among 3576 women, 2435 (68%) initiated EFV at a median 121.1 weeks post delivery. After EFV initiation, 2.5% (61/2435) had severe (grade 3 or higher) hepatotoxicity with an incidence of 2.3 (95% confidence interval [CI], 2.0–2.6) per 100 person-years. Events occurred between 1 and 132 weeks postpartum. Of those with severe hepatotoxicity, 8.2% (5/61) were symptomatic, and 3.3% (2/61) of those with severe hepatotoxicity died from EFV-related hepatotoxicity, 1 of whom was symptomatic. The incidence of liver-related mortality was 0.07 (95% CI, .06–.08) per 100 person-years. In multivariable analysis, older age was associated with severe hepatotoxicity (adjusted hazard ratio per 5 years, 1.35 [95% CI, 1.06–1.70]). Conclusions Severe hepatotoxicity after EFV initiation occurred in 2.5% of women and liver-related mortality occurred in 3% of those with severe hepatotoxicity. The occurrence of fatal events underscores the need for safer treatments for women of childbearing age.

scholarly journals In Vitro and In Vivo Efficacies of the New Triazole Albaconazole against Cryptococcus neoformans

2004 ◽  
Vol 48 (2) ◽  
pp. 384-387 ◽  
Author(s):  
J. L. Miller ◽  
W. A. Schell ◽  
E. A. Wills ◽  
D. L. Toffaletti ◽  
M. Boyce ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cerebrospinal Fluid ◽  
Cryptococcus Neoformans ◽  
Cryptococcal Meningitis ◽  
Rabbit Model ◽  
Weight Basis ◽  
Csf Penetration ◽  
Immunodeficiency Virus

ABSTRACT The activity of albaconazole (UR-9825; J. Uriach & Cía. S.A., Barcelona, Spain) was compared to that of fluconazole against 12 isolates of Cryptococcus neoformans in vitro and against 1 isolate in vivo in a rabbit model of cryptococcal meningitis. Albaconazole was 100-fold more potent in vitro than fluconazole on a per-weight basis and was fungicidal at potentially relevant concentrations for two isolates. MICs ranged from ≤0.0012 to 1.25 μg/ml, with the MICs for most isolates being between 0.039 and 0.156 μg/ml. Isolates were from human immunodeficiency virus (HIV)-infected and non-HIV-infected patients and were of serotypes A, B, and C; and the fluconazole MICs for some of the isolates were elevated. Infected rabbits were treated with either fluconazole or albaconazole at dosages ranging from 5 to 80 mg/kg of body weight/day. The peak concentrations of albaconazole in serum and cerebrospinal fluid (CSF) averaged 4.14 and 0.62 μg/ml, respectively, in animals receiving 80 mg/kg/day. Comparison of the concentrations in serum and CSF suggested a level of CSF penetration of approximately 15%. Despite limited penetration into the subarachnoid space, at all three doses tested albaconazole was as effective as fluconazole for the treatment of cryptococcal meningitis in rabbits.

Cancer in human immunodeficiency virus-infected children: a case series from the Children's Cancer Group and the National Cancer Institute.

1998 ◽  
Vol 16 (5) ◽  
pp. 1729-1735 ◽  
Author(s):  
M O Granovsky ◽  
B U Mueller ◽  
H S Nicholson ◽  
P S Rosenberg ◽  
C S Rabkin
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Cancer Diagnosis ◽  
National Cancer Institute ◽  
Death Rate ◽  
Proportional Hazards ◽  
Case Series ◽  
Cox Proportional Hazards ◽  
Cancer Group ◽  
Immunodeficiency Virus

PURPOSE To describe the spectrum of malignancies in human immunodeficiency virus (HIV)-infected children and the clinical outcome of patients with these tumors. METHODS We retrospectively surveyed the Children's Cancer Group (CCG) and the National Cancer Institute (NCI) for cases of cancer that occurred between July 1982 and February 1997 in children who were HIV seropositive before or at the time of cancer diagnosis. We used Kaplan-Meier survivorship curves, hazard function estimates, and Cox proportional hazards models to evaluate survival. RESULTS Sixty-four children (39 boys, 25 girls) with 65 tumors were reported. Thirty-seven children (58%) acquired HIV infection vertically (median age at cancer diagnosis, 4.3 years); 22 children (34%) acquired HIV through transfusion of blood or blood products (median age at cancer diagnosis, 13.4 years). Forty-two children (65%) had non-Hodgkin's lymphoma (NHL). Eleven children (17%) had leiomyosarcomas (or leiomyomas), which are otherwise exceptionally rare in children. Other malignancies included acute leukemia (five children), Kaposi's sarcoma (KS; three children), Hodgkin's disease (two children), vaginal carcinoma in situ (one child), and tracheal neuroendocrine carcinoma (one child). Median survival after NHL diagnosis was 6 months (range, 1 day to 89 months) and after leiomyosarcoma was 12 months (range, 10 days to 19 months). The average monthly death rate after NHL diagnosis was 12% in the first 6 months, which decreased to about 2% thereafter. In contrast, the monthly death rate after leiomyosarcoma diagnosis increased from 5% in the first 6 months to about 20% thereafter. CONCLUSION After NHL, leiomyosarcoma is the second leading cancer in children with HIV infection. Both cancers have high mortality rates; improved outcome for NHL, in particular, may depend on earlier diagnosis and therapy.

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