Fulminant Hepatic Failure as the Initial Presentation of Hodgkin Lymphoma in 4 Patients With Human Immunodeficiency Virus.

In the era of antiretroviral therapy (ART), Hodgkin Lymphoma (HL) is a common non-AIDS-defining cancer with increasing incidence in people with human immunodeficiency virus (PWH). Through review of these cases, we identify clinical patterns such as declining CD4 count despite ART, hyperbilirubinemia and recurrent fever, which preceded diagnosis. Identifying these important signs and symptoms may lead to earlier diagnosis and initiation of therapy. Fulminant hepatic failure limits the ability to give standard of care chemotherapy, likely jeopardizing outcomes in this patient population. Alternative bridging therapies should be considered until hepatic function improves.

Cancer in patients with and without HIV infection in the national cancer registry of Rwanda.

OBJECTIVE: As antiretroviral therapy (ART) has been widely scaled up in Rwanda, life expectancies among people with HIV (PWH) have increased. With increasing viral suppression, AIDS-defining cancers (ADCs) typically decrease; however, as the PWH population ages, non-AIDS-defining cancers (NADCs) will be expected to increase. The aim of this study was to compare cancer diagnoses between PWH and patients without HIV in Rwanda and to describe the changes in the number and types of cancer over time. DESIGN: Retrospective cohort study. METHODS: Rwanda National Cancer Registry (RNCR) recorded the HIV status, primary site, and morphological description for cancer diagnoses from 2007 to 2018. Descriptive analyses were carried out by cancer group (HIV+ and HIV-). A portion of patients whose HIV status was unknown (63%) were excluded from the present analysis. RESULTS: Among the 20 258 cases registered in the Registry, there were 1048 PWH and 6359 HIV- individuals. The proportion of ADCs were significantly higher in the PWH group compared to those without HIV ( P  < 0.001). Among PWH, there was a longitudinal increase in NADCs and a decrease in ADCs ( P  < 0.001) over time. Among the ADCs in the PWH group, there was a significant decline in Kaposi sarcoma cases over time. CONCLUSIONS: The study demonstrates a decreasing frequency of ADCs driven by declines in Kaposi sarcoma diagnoses and an increased frequency of NADCs among PWH in Rwanda over time. These findings support a need for focusing early detection and management efforts on NADCs, as they begin to play a larger role in the disease processes that affect the aging PWH population.

Nosocomial disseminated fusariosis in a hematopoietic stem cell transplant recipient.

We report a case of nosocomial disseminated Fusarium in a stem cell transplant recipient. Identification of hospital fungal water reservoirs with routine surveillance cultures could potentially decrease rates of invasive infection.

HHV-6 Encephalitis After Chimeric Antigen Receptor T-cell Therapy (CAR-T): 2 Case Reports and a Brief Review of the Literature.

Human herpesvirus 6 (HHV-6) reactivation can occur in patients who are highly immunosuppressed, including those who have undergone hematopoietic stem cell transplantation (HSCT). HHV-6 encephalitis is a severe manifestation that is well described in the HSCT population. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel cancer-directed immunotherapy that results in severe immunosuppression. Patients undergoing CAR-T therapy may be at risk for HHV-6 encephalitis, which can be difficult to distinguish from a common adverse effect of CAR-T therapy, neurotoxicity. Herein, we describe 2 patients diagnosed with HHV-6 encephalitis after CAR-T therapy and discuss the diagnostic approach and differential diagnosis for altered mental status after CAR-T therapy. Diagnosing HHV-6 encephalitis can be difficult in this patient population as altered mental status is common after CAR-T therapy and may be attributed to CAR-T-associated neurotoxicity.

CMV Infection in Hematopoietic Stem Cell Transplantation: Prevention and Treatment Strategies.

PURPOSE OF REVIEW: Cytomegalovirus (CMV) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (Allo-HSCT). New strategies and methods for prevention and management of CMV infection are urgently needed. We aim to review the new developments in diagnostics, prevention, and management strategies of CMV infection in Allo-HSCT recipients. RECENT FINDINGS: The approval of the novel anti-CMV drug letermovir in 2017 has led to an increase in the use of antiviral prophylaxis as a preferred approach for prevention in many centers. Real-world studies have shown efficacy similar to the clinical trial. CMV-specific T cell-mediated immunity assays identify patients with immune reconstitution and predict disease progression. Phase 2 trials of maribavir have shown its efficacy as preemptive therapy and treatment of resistant and refractory CMV infections. Adoptive T cell therapy is an emerging option for treatment of refractory and resistant CMV. Of the different CMV vaccine trials, PepVax has shown promising results in a phase 1 trial. SUMMARY: CMV cell-mediated immunity assays have potential to be used as an adjunctive test to develop individualized management plan by identifying the patients who develop immune reconstitution; however, further prospective interventional studies are needed. Maribavir and adoptive T cell therapy are promising new therapies for treatment of CMV infections. CMV vaccine trials for prevention are also under way.

Intravesicular Cidofovir in the Treatment of BK Virus-Associated Hemorrhagic Cystitis Following Hematopoietic Stem Cell Transplantation.

Background: BK virus hemorrhagic cystitis (BKV-HC) is a common complication following hematopoietic stem cell transplant (HSCT); optimal management remains uncertain. Supportive care (bladder irrigation and blood transfusions) and intravenous and intravesicular cidofovir have all been used with varying success. Objective: The purpose of this study was to determine the safety and effectiveness of intravesicular cidofovir for BKV-HC following HSCT. Methods: A retrospective analysis of all HSCT patients with BKV-HC prescribed intravesicular cidofovir from 2012 to 2017. Results: 33 patients were treated for BKV-HC. The median age was 50 years (range 23-73), and 18 (55%) were male. The median HC symptom severity was 2, with a median BK urine viral load pretreatment of 100,000,000 IU/mL. Patients received a median of 2 intravesicular treatments (range 1-7) at a dosage of 5 mg/kg per instillation. In all, 19 (59%) patients demonstrated complete clinical resolution of symptoms; 9 (28%) had a partial response; and 4 (13%) had no change in symptoms. Patients with a high pretreatment BK viral load (>100 million) and high HC grade (2-4) had a lower frequency of complete remission. The main side effect of intravesicular instillation was severe bladder spasms in 4 patients (12%). Conclusion and Relevance: This is the largest study of intravesicular cidofovir treatment of BKV HC reported to date; 88% of patients with BVK-HC achieved clinical improvement of symptoms with minimal side effects. Clinical trials of intravesicular cidofovir could provide further evidence for this treatment for BKV-HC.

Case-control study of PD-1, PD-L1 and B7-H3 expression in lung cancer patients with and without human immunodeficiency virus (HIV) infection.

OBJECTIVE: Co-signaling molecules PD-L1, B7-H3, and PD-1 play a key role in cancer immunology. There are limited but emerging data on expression of these molecules in HIV-infected lung cancer patients. MATERIALS AND METHODS: We reviewed archived lung cancer tissue samples from HIV-infected cases (n = 13) and HIV-uninfected controls (n = 13) from 2001-2015. Cases and controls were matched by histology and stage. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 and B7-H3, and percent of tumor infiltrating immune cells (TII) expressing PD-1 and PD-L1. Positive expression was defined as >5%. Statistical analysis was performed using the non-parametric Mann-Whitney test and the chi-square test. RESULTS: PD-L1 expression on tumor cells was positive in 23% of cases and 46% of controls. B7-H3 expression on tumor cells was positive in 92% of cases and 69% of controls. PD-1 expression on TII was positive in 69% of cases and 54% of controls. PD-L1 expression on TII was positive in 31% of cases and 69% of controls. B7-H3 percent expression on tumor cells was significantly higher in cases vs. controls (median 90% vs 20%, p = 0.005), but there were no significant differences in percent expression of PD-L1 on tumor cells, PD-1 on TII or PD-L1 on TII. CONCLUSION: HIV-infected lung cancer patients had significantly higher B7-H3 tumor expression compared to HIV-uninfected controls, with similar rates of tumor PD-L1 expression, as well as PD-1 and PD-L1 expression on TII. These results support inclusion of HIV-infected lung cancer patients in future immunotherapy trials.

Gynecologic cancer in HIV-infected women: treatment and outcomes in a multi-institutional cohort.

OBJECTIVE: To evaluate gynecologic cancer treatments in HIV-infected women for adherence to National Comprehensive Cancer Network (NCCN) guidelines and to describe survival by adherence to guidelines. DESIGN: Beyond cervical cancer, there are little data on treatment and outcomes for these women. This is a retrospective cohort study of HIV-infected women with gynecologic cancers. METHODS: HIV-infected women with gynecologic cancers from 2000 to 2015 were identified at two urban, comprehensive cancer centers. Chart reviews extracted demographic, HIV, and cancer-related variables. Cancer treatment was evaluated for adherence to NCCN guidelines. Overall survival was compared between those who received NCCN adherent and nonadherent cancer care. RESULTS: Fifty-seven women were identified; 15 vulvar (26%), 26 cervical (46%), nine ovarian (16%), and seven endometrial (12%) cancers. Median time from HIV to cancer diagnosis was 8.5 years, and 88% of women were black. Thirty patients (53%) had stage I, and 27 (47%) had stage II-IV disease. Overall, 28 women (49%) received NCCN-adherent care; 22 of 30 stage I (73%) and six of 27 stage II-IV patients (22%). Among 29 women not receiving NCCN-adherent care, 69% were due to patient-related factors or toxicity. Among women with II-IV cancers, 48-month survival was higher in women who received NCCN-adherent care than those who did not (60 versus 28%). CONCLUSION: Most HIV-infected women with advanced gynecologic cancers did not receive NCCN-adherent care and had worse survival compared to those who did. Focus on treatment-related toxicities and patient-related barriers to cancer care are necessary in this population.

Virologic and Immunologic Outcomes in HIV-Infected Patients with Cancer.

Achievement and maintenance of virologic suppression after cancer diagnosis have been associated with improved outcomes in HIV-infected patients, but few studies have analyzed the virologic and immunologic outcomes after a cancer diagnosis. All HIV-infected patients with a diagnosis of cancer between 2000 and 2011 in an urban clinic population in Baltimore, MD, were included for review. HIV-related outcomes (HIV-1 RNA viral load and CD4 cell count) were abstracted and compared for patients with non-AIDS-defining cancers (NADCs) and AIDS-defining cancers (ADCs). Four hundred twelve patients with baseline CD4 or HIV-1 RNA viral load data were analyzed. There were 122 (30%) diagnoses of ADCs and 290 (70%) NADCs. Patients with NADCs had a higher median age (54 years vs. 43 years, p < .0001) and a higher frequency of hepatitis C coinfection (52% vs. 36%, p = .002). The median baseline CD4 was lower for patients with ADCs (137 cells/mm3 vs. 314 cells/mm3) and patients with NADCs were more likely to be suppressed at cancer diagnosis (59% vs. 25%) (both p < .0001). The median CD4 for patients with NADCs was significantly higher than patients with ADCs at 6 and 12 months after diagnosis and higher at 18 and 24 months, but not significantly. Patients with an NADC had 2.19 times (95% CI 1.04-4.62) the adjusted odds of being suppressed at 12 months and 2.17 times the odds (95% CI 0.92-5.16) at 24 months compared to patients with an ADC diagnosis. For patients diagnosed with ADCs and NADCs in this urban clinic setting, both virologic suppression and immunologic recovery improved over time. Patients with NADCs had the highest odds of virologic suppression in the 2 years following cancer diagnosis.

Colonoscopy Findings in HIV-Infected Men and Women from an Urban U.S. Cohort Compared with Non-HIV-Infected Men and Women.

INTRODUCTION: As HIV-infected patients live longer, non-AIDS-defining cancers are now a major cause of morbidity and mortality. The purpose of this study was to compare the prevalence, type, and location of colorectal neoplastic lesions found on colonoscopy in HIV-infected patients from an urban U.S. cohort with non-HIV-infected patients. METHODS: We collected clinical data and colonoscopy findings on 263 HIV-infected patients matched with 657 non-HIV-infected patients on age, race, and sex. Frequency distributions and descriptive statistics were used to characterize the study population. The primary exposure was HIV infection, and the primary outcome was any adenoma or adenocarcinoma. Logistic regression models were used to estimate odds ratios with 95% confidence intervals (CIs). RESULTS: Participants were primarily African American and 40% were women. HIV-infected patients were less likely to have any neoplastic lesions (21.3% vs. 27.7%, p < .05), adenoma (20.5% vs. 27.1%, p = .04), tubular adenomas >10 mm (0.4% vs. 2.9%, p = .02), and serrated adenomas (0.0% vs.2.6%, p = <.01). There was a nonsignificant increased prevalence of adenocarcinoma in HIV-infected individuals compared with non-HIV-infected individuals (1.5% vs. 0.8%, p = .29). The lower prevalence of any adenoma remained after controlling for age, sex, smoking status, body-mass index, and diabetes mellitus [adjusted odds ratio (aOR), 0.61; 95% CI, 0.43-0.88]. HIV-infected patients had a lower prevalence of colorectal neoplastic lesions, including high-risk adenomas, than non-HIV-infected patients. CONCLUSIONS: Our findings suggest that HIV infection in a primarily African American population is associated with a lower prevalence of colorectal adenomas, but not adenocarcinoma, found by colonoscopy.

TRACnet Internet and Short Message Service Technology Improves Time to Antiretroviral Therapy Initiation Among HIV-infected Infants in Rwanda.

BACKGROUND: Delays in testing HIV-exposed infants and obtaining results in resource-limited settings contribute to delays for initiating antiretroviral therapy (ART) in infants. To overcome this challenge, Rwanda expanded its national mobile and Internet-based HIV/AIDS informatics system, called TRACnet, to include HIV polymerase chain reaction (PCR) results in 2010. This study was performed to evaluate the impact of TRACnet technology on the time to delivery of test results and the subsequent initiation of ART in HIV-infected infants. METHODS: A retrospective cohort study was conducted on 380 infants who initiated ART in 190 health facilities in Rwanda from March 2010 to June 2013. Program data collected by the TRACnet system were extracted and analyzed. RESULTS: Since the introduction of TRACnet for processing PCR results, the time to receive results has significantly decreased from a median of 144 days [interquartile range (IQR): 121-197 days] to 23 days (IQR: 17-43 days). The number of days between PCR sampling and health facility receipt of results decreased substantially from a median of 90 days (IQR: 83-158 days) to 5 days (IQR: 2-8 days). After receiving PCR results at a health facility, it takes a median of 44 days (IQR: 32-77 days) before ART initiation. Result turnaround time was significantly associated with time to initiating ART (P < 0.001). An increased number of staff trained for HIV care and treatment was also significantly associated with decreased time to ART initiation (P = 0.004). CONCLUSIONS: The use of mobile technology for communication of HIV PCR results, coupled with well-trained and skilled personnel, can reduce delays in communicating results to providers. Such reductions may improve timely ART initiation in resource-limited settings.

Cryptococcus neoformans infection in malignancy.

Cryptococcosis is an opportunistic invasive fungal infection that is well described and easily recognised when it occurs as meningitis in HIV-infected persons. Malignancy and its treatment may also confer a higher risk of infection with Cryptococcus neoformans, but this association has not been as well described. A case of cryptococcosis in a cancer patient is presented, and all cases of coincident C. neoformans infection and malignancy in adults published in the literature in English between 1970 and 2014 are reviewed. Data from these cases were aggregated in order to describe the demographics, type of malignancy, site of infection, clinical manifestations, treatment and outcomes of cryptococcosis in patients with cancer. Haematologic malignancies accounted for 82% of cases, with lymphomas over-represented compared to US population data (66% vs. 53% respectively). Cryptococcosis was reported rarely in patients with solid tumours. Haematologic malignancy patients were more likely to have central nervous system (P < 0.001) or disseminated disease (P < 0.001), receive Amphotericin B as part of initial therapy (P = 0.023), and had higher reported mortality rates than those with solid tumours (P = 0.222). Providers should have heightened awareness of the possibility of cryptococcosis in patients with haematologic malignancy presenting with infection.

HIV-associated lymphoma sub-type distribution, immunophenotypes and survival in an urban clinic population.

HIV-infected patients have an increased risk for both Hodgkin and non-Hodgkin lymphomas. A retrospective cohort of all HIV-infected patients diagnosed with lymphoma in urban clinics from 2000-2013 was evaluated to characterize the distribution and determine effects of sub-type and immunophenotype on survival. Of 160 cases identified, 131 (82%) had complete information and were analyzed. The most common sub-types were diffuse large B cell (41%), Burkitt (21%) and Hodgkin lymphoma (18%). Advanced (78% stage III/IV) and extranodal disease (82%) at presentation were common. CD20 was the most commonly expressed immunophenotypic marker (89%). Overall mortality rate was high (26.1 per 100 person-years). Lower mortality was noted in CD10 + and CD20 + lymphomas, but differences were not statistically significant. After adjustment, low CD4 count (≤ 200) at diagnosis was associated with higher mortality (adjusted hazard ration (AHR) = 1.75; 95% CI = 1.00-3.61). Mortality in this cohort of patients with HIV-associated lymphomas was high and exceeds that from published data from the general population.

Patterns of HIV viremia and viral suppression before diagnosis of non-AIDS-defining cancers in HIV-infected individuals.

BACKGROUND: The association between HIV viremia and non-AIDS-defining cancers (NADCs) is not well characterized. Viremia may contribute directly or indirectly to cancer development and may have a differential impact on various cancer types. Our objective was to characterize patterns of HIV viremia in a retrospective, urban, clinical cohort (N = 320) of patients diagnosed with NADCs. FINDINGS: The most common NADC's were lung (n = 60), prostate (n = 47), oropharyngeal (n = 32), liver (n = 29), and anal cancer (n = 20) and Hodgkin lymphoma (n = 18). In the year before cancer diagnosis, 66 % of all patients were virally suppressed. Patients with oropharyngeal (70 %) and prostate cancer (78 %) had a higher proportion of visits with suppressed viral loads. Patients diagnosed with anal cancer and Hodgkin lymphoma were infrequently virally suppressed and more frequently had viral loads ≥5 log10 copies/ml in the ten years prior to cancer diagnosis. CONCLUSIONS: In this cohort of HIV-infected patients diagnosed with NADCs, there were important differences in the patterns and levels of viremia between the different NADCs in the ten years prior to cancer diagnosis. Patients with anal cancer and Hodgkin lymphoma had the highest proportion of high level viremia in the ten years before cancer and the lowest frequency of viral load suppression at cancer diagnosis.

Anal Cancer Screening in an Urban HIV Clinic: Provider Perceptions and Practice.

In this article, we sought to understand the perceptions and practice of providers on anal cancer screening in HIV-infected patients. Providers in an academic outpatient HIV practice were surveyed. Data were analyzed to determine the acceptability and perceptions of providers on anal Papanicolaou tests. Survey response rate was 55.3% (60.7% among male and 47.4% among female providers). One-third of the providers had received screening requests from patients. Female providers had higher self-rated comfort with anal Papanicolaou tests, with a mean score of 7.1 (95% confidence interval [CI] 4.7-9.5) compared to 3.6 (95% CI 1.5-5.7) for male providers, P = .02. Sixty-seven percent of male providers and 37.5% of female providers would like to refer their patients for screening rather than perform the test themselves. Only 54.2% of our providers have ever performed anal cytology examination. Our survey revealed that not all providers were comfortable performing anal cancer screening for their patients.