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

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

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1016 ◽

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.

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

Clinical Infectious Diseases ◽

10.1093/cid/ciaa037 ◽

2020 ◽

Cited By ~ 1

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 > 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.

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

Clinical Infectious Diseases ◽

10.1093/cid/ciaa244 ◽

2020 ◽

Cited By ~ 1

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.

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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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofw089 ◽

2016 ◽

Vol 3 (2) ◽

Cited By ~ 6

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.

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Timeliness of Human Immunodeficiency Virus Diagnosis and Antiretroviral Treatment Initiation in the Era of Universal Testing and Treatment

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz148 ◽

2019 ◽

Vol 220 (4) ◽

pp. 648-656 ◽

Cited By ~ 3

Author(s):

McKaylee M Robertson ◽

Sarah L Braunstein ◽

Donald R Hoover ◽

Sheng Li ◽

Denis Nash

Keyword(s):

Human Immunodeficiency Virus ◽

Hiv Infection ◽

Antiretroviral Treatment ◽

Proportional Hazards ◽

Treatment Initiation ◽

Hiv Diagnosis ◽

Acute Hiv Infection ◽

Art Initiation ◽

Universal Testing ◽

Immunodeficiency Virus

Abstract Background We describe the timing of human immunodeficiency virus (HIV) diagnosis and antiretroviral treatment (ART) initiation after implementation of universal testing and treatment policies in New York City (NYC). Methods Using NYC population-based HIV registry data for persons with HIV diagnosed from 2012 through 2015 and followed up through June 2017, we examined trends in the proportion with diagnosis soon after HIV infection (ie, with CD4 cell count ≥500/μL or with acute HIV infection) and used Kaplan-Meier plots and proportional hazards regression to examine the timing of ART initiation after diagnosis. Results Among 9987 NYC residents with HIV diagnosed from 2012 to 2015, diagnosis was early in 35%, and 87% started ART by June 2017. The annual proportion of persons with early diagnosis did not increase appreciably (35% in 2012 vs 37% in 2015; P = .08). By 6 months after diagnosis, 62%, 67%, 72% and 77% of persons with HIV diagnosed in 2012, 2013, 2014, or 2015, respectively, had started ART, with median (interquartile range) times to ART initiation of 3.34 (1.34–12.75), 2.62 (1.28–10.13), 2.16 (1.15–7.11), and 2.03 (1.11–5.61) months, respectively. Conclusions Although recommendations for ART initiation on diagnosis are increasingly being implemented, the findings of the current study suggest that immediate treatment initiation is not universal. Continued efforts are needed to expand and better target HIV testing to promote earlier diagnosis.

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Non-therapeutic male circumcision in infancy or childhood and risk of human immunodeficiency virus and other sexually transmitted infections: national cohort study in Denmark

European Journal of Epidemiology ◽

10.1007/s10654-021-00809-6 ◽

2021 ◽

Author(s):

Morten Frisch ◽

Jacob Simonsen

Keyword(s):

Human Immunodeficiency Virus ◽

Cohort Study ◽

Sexually Transmitted Infections ◽

Male Circumcision ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Anogenital Warts ◽

Sexually Transmitted ◽

Immunodeficiency Virus ◽

National Cohort

AbstractWhether male circumcision in infancy or childhood provides protection against the acquisition of human immunodeficiency virus (HIV) or other sexually transmitted infections (STIs) in adulthood remains to be established. In the first national cohort study to address this issue, we identified 810,719 non-Muslim males born in Denmark between 1977 and 2003 and followed them over the age span 0–36 years between 1977 and 2013. We obtained information about cohort members’ non-therapeutic circumcisions, HIV diagnoses and other STI outcomes from national health registers and used Cox proportional hazards regression analyses to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) associated with foreskin status (i.e., circumcised v. genitally intact). During a mean of 22 years of follow-up, amounting to a total observation period of 17.7 million person-years, 3375 cohort members (0.42%) underwent non-therapeutic circumcision, and 8531 (1.05%) received hospital care for HIV or other STIs. Compared with genitally intact males, rates among circumcised males were not statistically significantly reduced for any specific STI. Indeed, circumcised males had a 53% higher rate of STIs overall (HR = 1.53, 95% CI: 1.24–1.89), and rates were statistically significantly increased for anogenital warts (74 cases in circumcised males v. 7151 cases in intact males, HR = 1.51; 95% CI: 1.20–1.90) and syphilis (four cases in circumcised males v. 197 cases in intact males, HR = 3.32; 95% CI: 1.23–8.95). In this national cohort study spanning more than three decades of observation, non-therapeutic circumcision in infancy or childhood did not appear to provide protection against HIV or other STIs in males up to the age of 36 years. Rather, non-therapeutic circumcision was associated with higher STI rates overall, particularly for anogenital warts and syphilis.

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Colorectal Disorders in Acute Human Immunodeficiency Virus Infection: A Case Series

Open Forum Infectious Diseases ◽

10.1093/ofid/ofw014 ◽

2016 ◽

Vol 3 (1) ◽

Cited By ~ 1

Author(s):

Theppharit Panichsillapakit ◽

Derek Patel ◽

Joanne Santangelo ◽

Douglas D. Richman ◽

Susan J. Little ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hiv Infection ◽

Acute Infection ◽

Case Series ◽

Low Grade ◽

Gi Tract ◽

Acute Hiv Infection ◽

First Case ◽

Immunodeficiency Virus ◽

Acute Hiv

Abstract Background. The gastrointestinal (GI) tract is important in the pathogenesis of human immunodeficiency virus (HIV) infection. We report a case series of lower GI endoscopic and histopathologic findings of HIV-infected individuals after presentation with acute infection. Methods. We performed a retrospective case review of individuals infected with HIV who enrolled between August 2010 and April 2013 in a primary infection treatment trial. All participants started the trial during acute infection and underwent colonoscopy with biopsies at baseline and after the start of antiretroviral treatment. Results. Twenty acutely infected individuals were included in the study (mean age, 33 years; range, 20–54 years). All participants were male who reported having receptive anal sex as an HIV risk factor. Nine individuals (45%) had at least 1 finding by colorectal pathology; 1 person had 2 diagnoses (diverticulosis and focal active proctitis). The histopathological findings revealed anal dysplasia in 3 cases: 2 had high-grade anal intraepithelial neoplasia (AIN) and 1 had low-grade AIN. Two persons had a colorectal polyp, 1 hyperplastic and 1 adenomatous. Three persons were diagnosed with diverticulosis, and 2 persons were diagnosed with proctitis, including 1 with focal active proctitis and 1 with cytomegalovirus proctitis. Conclusions. To our knowledge, this is the first case series report of lower GI disorders in acute HIV-infected individuals. Although the causal relationship remains uncertain, we describe the endoscopic findings that were observed during acute HIV infection among men who have sex with men. Understanding the prevalence of these pathologies may likely shed light on how acute HIV infection damages the lower GI tract.

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An association between clotting factor concentrates use and mortality in human immunodeficiency virus-infected hemophilic patients

Blood ◽

10.1182/blood.v86.6.2213.bloodjournal8662213 ◽

1995 ◽

Vol 86 (6) ◽

pp. 2213-2219 ◽

Cited By ~ 8

Author(s):

JB Montoro ◽

J Oliveras ◽

JI Lorenzo ◽

JM Tusell ◽

C Altisent ◽

...

Keyword(s):

Risk Factors ◽

Human Immunodeficiency Virus ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Clotting Factor ◽

Individual Risk ◽

Immunodeficiency Virus ◽

Clotting Factor Concentrates ◽

The Impact

There is much evidence that clotting factor concentrates (CFC), especially the so-called intermediate-purity preparations, exert an immunomodulating effect in vitro. The impact of this effect on the outcome of human immunodeficiency virus (HIV) infection in hemophiliacs is still controversial. In this retrospective cohort study, the effects of treatment with CFC on mortality and progression to acquired immunodeficiency syndrome (AIDS) were estimated while controlling for individual risk factors. Logistic regression and survival analysis, including the Cox proportional-hazards regression model, were performed with data from a 11-year follow-up of 225 hemophilic patients seropositive for HIV type 1 (HIV-1) of two hemophilia centers. Mortality and progression to AIDS rates were strongly associated with lower administration of CFC. After adjusting for age, a statistically significant and robust association was observed. The use of CFC was negatively associated with progression to AIDS (P = .0252) and mortality (P = .0033). The adjusted relative hazards of mortality and progression to AIDS rate between the most treated patients (> 700 IU/kg/yr) versus the least treated (< or = 700 IU/kg/yr) were 0.53 (confidence limits, 0.33 to 0.86) and 0.57 (0.39 to 0.84), respectively. Although the effects of other unmeasured risk factors cannot be excluded with certainty, these results suggest that there is a negative association between treatment with CFC and progression to AIDS and mortality.

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz478 ◽

2019 ◽

Vol 6 (11) ◽

Cited By ~ 2

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.

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