RESUMO
BACKGROUND: Although immunotherapy has emerged as a therapeutic strategy for many cancers, there are limited studies establishing the safety and efficacy in people living with HIV (PLWH) and cancer. METHODS: PLWH and solid tumors or Kaposi sarcoma (KS) receiving antiretroviral therapy and a suppressed HIV viral load received nivolumab at 3 mg/kg every 2 weeks, in two dose deescalation cohorts stratified by CD4 count (stratum 1: CD4 count > 200/µL and stratum 2: CD4 count 100-199/µL). An expansion cohort of 24 participants with a CD4 count > 200/µL was then enrolled. RESULTS: A total of 36 PLWH received nivolumab, including 15 with KS and 21 with a variety of other solid tumors. None of the first 12 participants had dose-limiting toxicity in both CD4 strata, and five patients (14%) overall had grade 3 or higher immune related adverse events. Objective partial response occurred in nine PLWH and cancer (25%), including in six of 15 with KS (40%; 95% CI, 16.3-64.7). The median duration of response was 9.0 months overall and 12.5 months in KS. Responses were observed regardless of PDL1 expression. There were no significant changes in CD4 count or HIV viral load. CONCLUSIONS: Nivolumab has a safety profile in PLWH similar to HIV-negative subjects with cancer, and also efficacy in KS. Plasma HIV remained suppressed and CD4 counts remained stable during treatment and antiretroviral therapy, indicating no adverse impact on immune function. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02408861.
Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Sarcoma de Kaposi , Humanos , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Nivolumabe/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Sarcoma de Kaposi/tratamento farmacológico , Contagem de Linfócito CD4 , Carga ViralRESUMO
PURPOSE: To determine whether treatment of anal high-grade squamous intraepithelial lesions (HSIL), vs active monitoring, is effective in reducing incidence of anal cancer in persons living with HIV, the US National Cancer Institute funded the Phase III ANal Cancer/HSIL Outcomes Research (ANCHOR) clinical trial. As no established patient-reported outcomes (PRO) tool exists for persons with anal HSIL, we sought to estimate the construct validity and responsiveness of the ANCHOR Health-Related Symptom Index (A-HRSI). METHODS: The construct validity phase enrolled ANCHOR participants who were within two weeks of randomization to complete A-HRSI and legacy PRO questionnaires at a single time point. The responsiveness phase enrolled a separate cohort of ANCHOR participants who were not yet randomized to complete A-HRSI at three time points: prior to randomization (T1), 14-70 (T2), and 71-112 (T3) days following randomization. RESULTS: Confirmatory factor analysis techniques established a three-factor model (i.e., physical symptoms, impact on physical functioning, impact on psychological functioning), with moderate evidence of convergent validity and strong evidence of discriminant validity in the construct validity phase (n = 303). We observed a significant moderate effect for changes in A-HRSI impact on physical functioning (standardized response mean = 0.52) and psychological symptoms (standardized response mean = 0.60) from T2 (n = 86) to T3 (n = 92), providing evidence of responsiveness. CONCLUSION: A-HRSI is a brief PRO index that captures health-related symptoms and impacts related to anal HSIL. This instrument may have broad applicability in other contexts assessing individuals with anal HSIL, which may ultimately help improve clinical care and assist providers and patients with medical decision-making.
Assuntos
Neoplasias do Ânus , Infecções por HIV , Lesões Intraepiteliais Escamosas , Humanos , Qualidade de Vida/psicologia , Lesões Intraepiteliais Escamosas/diagnóstico , Lesões Intraepiteliais Escamosas/patologia , Canal Anal , Inquéritos e Questionários , Neoplasias do Ânus/patologia , Infecções por HIV/patologiaRESUMO
Emerging evidence shows that tumor cells secrete extracellular vesicles (EVs) that carry bioactive cell surface markers, such as programmed death-ligand 1 (PD-L1), which can modulate immune responses and inhibit anti-tumor responses, potentially playing a role in lymphomagenesis and in promoting the growth of these cancers. In this study, we investigated the role of EVs expressing cell surface molecules associated with B cell activation and immune regulation. We measured levels of EVs derived from plasma from 57 subjects with AIDS-related non-Hodgkin lymphoma (AIDS-NHL) enrolled in the AIDS Malignancies Consortium (AMC) 034 clinical trial at baseline and post-treatment with rituximab plus concurrent infusional EPOCH chemotherapy. We found that plasma levels of EVs expressing PD-L1, CD40, CD40L or TNF-RII were significantly reduced after cancer treatment. AIDS-NHL patients with the diffuse large B cell lymphoma (DLBCL) tumor subtype had decreased plasma levels of EVs bearing PD-L1, compared to those with Burkitt's lymphoma. CD40, CD40L and TNF-RII-expressing EVs showed a significant positive correlation with plasma levels of IL-10, CXCL13, sCD25, sTNF-RII and IL-18. Our results suggest that patients with AIDS-NHL have higher levels of EVs expressing PD-L1, CD40, CD40L or TNF-RII in circulation before cancer treatment and that levels of these EVs are associated with levels of biomarkers of microbial translocation and inflammation.
Assuntos
Síndrome da Imunodeficiência Adquirida , Vesículas Extracelulares , Linfoma Relacionado a AIDS , Antígeno B7-H1 , Antígenos CD40 , Ligante de CD40 , Humanos , Receptores Tipo II do Fator de Necrose TumoralRESUMO
BACKGROUND: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking. METHODS: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer. RESULTS: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test). CONCLUSIONS: Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).
Assuntos
Neoplasias do Ânus , Infecções por HIV , Lesões Pré-Cancerosas , Lesões Intraepiteliais Escamosas , Conduta Expectante , Adulto , Neoplasias do Ânus/etiologia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/prevenção & controle , Neoplasias do Ânus/terapia , Biópsia , Feminino , Infecções por HIV/complicações , Homossexualidade Masculina , Humanos , Masculino , Infecções por Papillomavirus/complicações , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/terapia , Estudos Prospectivos , Lesões Intraepiteliais Escamosas/etiologia , Lesões Intraepiteliais Escamosas/patologia , Lesões Intraepiteliais Escamosas/terapiaRESUMO
PURPOSE: Program evaluation to describe nursing hours per patient day (NHPPD) within the Veterans Health Administration (VHA) and to evaluate Staffing Methodology in the VHA Community Living Centers (CLCs). METHODS: Targeted and actual NHPPD were compiled retrospectively for each VHA CLC unit over a one-year timeframe for calendar year 2019. For descriptive analyses, actual NHPPD were averaged across months for each CLC unit. RESULTS: The mean for actual hours as a percent of target was 121.6% (95% CI, 118.5 to 124.7%) indicating the units' average hours across 2019 were 21.6% significantly higher than target. The actual NHPPD significantly differed across months (p<0.001) with the 2019 months of January and October having the highest NHPPD. CONCLUSIONS: Veteran safety is a VHA priority and appropriate nurse staffing is key to providing care that improves Veteran outcomes. Further exploration is needed on the impact of nurse staffing on Veteran outcomes, safety, and satisfaction.
Assuntos
Saúde dos Veteranos , Veteranos , Humanos , Admissão e Escalonamento de Pessoal , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Estados Unidos , Recursos HumanosAssuntos
Radiologia , Estudantes de Medicina , Escolha da Profissão , Humanos , Radiografia , Radiologia/educaçãoRESUMO
PURPOSE: The purpose of this quality improvement project was to examine the feasibility of rapidly converting a Tai Chi program for older Veterans from face-to-face to virtual classes. METHODS: Eighteen Veterans attending our face-to-face Tai Chi course were invited to transition to virtual classes. Feasibility was defined as the ability of program staff and participants to successfully connect and complete the initial and subsequent classes by VA Video Connect (VVC) with little to no technical difficulties, participant ability to participate in the course without safety concerns, and favorable feedback from participants and program staff. RESULTS: Nine of 18 Veterans agreed to transition to the virtual program and attended a median (interquartile range) of 11 (4-15) classes; they were younger (62.7 + 11.5 vs. 70.5 + 7.0 years, p < .05) and more likely to have the knowledge and equipment needed to participate (78% vs. 0%, p < .01) than nonparticipants. Tai Chi instructors and participating Veterans reported being able to connect to and complete the classes virtually with only minimal technical problems. No adverse events were reported. Feedback from the instructors and Veterans was positive and included comments on ease of use and enjoyability. CONCLUSION: Results suggest that virtual Tai Chi classes via VVC are feasible for some older Veterans.
Assuntos
COVID-19 , Tai Chi Chuan , Veteranos , Humanos , Pandemias , Melhoria de QualidadeRESUMO
It is well established that persons living with HIV (PLWH) have highly elevated rates of anal HSIL and anal cancer compared with those who are not living with HIV. The 5-year risk of anal cancer following anal HSIL has been reported to be as high as 14.1% among PLWH compared with 3.2% among those who are not living with HIV. To address these concerns, the AIDS Malignancy Consortium completed a large-scale, randomized trial to compare strategies for the prevention of anal cancer among PLWH with anal HSIL. The objective of the study was to determine whether treating anal HSIL was effective in reducing the incidence of anal cancer in PLWH compared with active monitoring. This paper describes the design of the ANal Cancer/HSIL Outcomes Research Study (ANCHOR) with respect to estimating the anal cancer event rate in this high risk population.
Assuntos
Neoplasias do Ânus , Infecções por HIV , Infecções por Papillomavirus , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/prevenção & controle , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Avaliação de Resultados em Cuidados de Saúde , Infecções por Papillomavirus/epidemiologia , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
PURPOSE: Evaluate the effectiveness of compression while receiving chemotherapy compared with chemotherapy alone in the treatment of HIV-associated Kaposi sarcoma (KS) lymphedema. METHODS: A randomized controlled trial was conducted in a single oncology clinic in western Kenya (NCT03404297). A computer-generated randomization schedule was used to allocate treatment arms. Randomized block design was used for stratification by lymphedema stage. Participants were HIV positive adults age ≥ 18 years on antiretroviral therapy with biopsy-proven KS associated with leg lymphedema and being initiated on chemotherapy. The intervention was 10 weeks of weekly clinic-based application of two-component paste compression bandages. The primary outcome was change in the Lower Extremity Lymphedema Index (LELI) score from week 0 to week 14. The secondary outcomes were change in the Lymphedema Quality of Life measure (LYMQOL) and change in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 score from week 0 to week 14. Blinded outcome assessments were conducted. RESULTS: Of 30 participants randomly assigned, 25 eligible patients (chemotherapy [control], n = 13; compression plus chemotherapy [intervention], n = 12) returned at week 14. Change in LELI, LYMQOL, and EORTC QLQ-C30 scores between week 14 and week 0 did not significantly differ by arm. The mean (standard deviation) change in LELI score was -25.9 (34.6) for the control arm compared with -13.3 (29.5) for the intervention arm, P = .340. The difference (95% CI) in the change in LELI score was -12.6 (-39.3 to 14.1). CONCLUSION: Future studies evaluating a 14-week change in LELI for KS lymphedema should assume a standard deviation of approximately 30. Lessons learned from this pilot trial should inform the development of a larger, multicenter trial to evaluate the effectiveness of compression for KS lymphedema.
Assuntos
Infecções por HIV , Linfedema , Sarcoma de Kaposi , Adolescente , Adulto , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Quênia , Perna (Membro) , Linfedema/complicações , Linfedema/terapia , Qualidade de Vida , Sarcoma de Kaposi/tratamento farmacológico , Sarcoma de Kaposi/terapiaRESUMO
BACKGROUND: Substance use disorders are a leading cause of morbidity and mortality in the United States, with opioid use disorder representing a growing public health concern and economic burden. Veterans within the Veterans Health Administration are impacted by opioid use disorder. SIGNIFICANCE: A common medication-assisted treatment is sublingual Suboxone (buprenorphine/naloxone) used in combination with behavior modification therapy. Missed Suboxone doses may lead to withdrawal and potential drug diversion. Sublocade (buprenorphine extended-release) is an alternative once-monthly subcutaneous injection administered by a healthcare provider. The purpose of this quality improvement project was to examine the effects of Sublocade on cravings in veterans with opioid use disorder. METHODS: Veterans were considered for Sublocade monthly injections if they were enrolled in the Suboxone program, not taking Suboxone as prescribed, and disenrolled from the Suboxone program more than 2 times. Cravings were measured before and after Sublocade program enrollment. RESULTS: Fifteen veterans were enrolled in the Sublocade program over a 12-month timeframe. Most were male (93%) with a median (range) age of 42 (33-62) years. The following were the primary opioids used before enrollment in the substance use disorder program: hydrocodone (47%), oxycodone (20%), and heroin (20%). Sublocade significantly reduced cravings (p = .001). In this small group, cravings were fully eliminated. DISCUSSION: Recent studies have shown Sublocade effectively blocks the effects of other opioids and minimizes the risk of medication diversion that occurs with Suboxone. For these reasons, Sublocade is an alternative medication-assisted treatment for veterans with opioid use disorder.
Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Veteranos , Masculino , Humanos , Estados Unidos , Adulto , Pessoa de Meia-Idade , Feminino , Combinação Buprenorfina e Naloxona/uso terapêutico , Buprenorfina/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Resultado do Tratamento , Antagonistas de Entorpecentes/uso terapêuticoRESUMO
BACKGROUND: Oral human papillomavirus (HPV) infection has been causally linked to a subset of oropharyngeal cancers in Western populations, and both oropharyngeal cancer and oral HPV infection are increased among HIV-positive individuals. India has high incidences of oral and oropharyngeal cancers, and Indian HIV-positive men who have sex with men (MSM) may be at increased risk of developing oropharyngeal cancers. However, there is little information available on the prevalence of oral HPV in this population. METHODS: We tested 302 HIV-positive Indian MSM for oral HPV infection using L1 HPV DNA PCR with probes specific for 29 types and a mixture of 10 additional types. CD4+ level and plasma HIV viral load (VL) were measured. Participants completed an interviewer-administered questionnaire including a sexual history. RESULTS: The prevalence of oral HPV was 23.7% (95% CI: 19-29%) and 2.4% of participants had oncogenic HPV types. No participants had oral HPV type 16 (HPV-16) and the prevalence of other anogenital HPV types was low. Participants with higher CD4+ levels had reduced odds of having any oral HPV infection (OR: 3.1 [1.4-6.9]) in multivariable analyses. CONCLUSIONS: This is the first report of oral HPV among Indian HIV-positive MSM. Our results show a high prevalence of oral HPV infection consistent with studies from Western populations. However, oncogenic anogenital HPV types were relatively uncommon in our study population. It is unknown what the impact of this distribution of oral HPV will be on oropharyngeal cancers. HIV-positive MSM in India should be monitored closely for oral and oropharyngeal pre-cancer and cancer.
Assuntos
Infecções por HIV/complicações , Doenças da Boca/epidemiologia , Infecções por Papillomavirus/epidemiologia , Minorias Sexuais e de Gênero , Estudos Transversais , Soropositividade para HIV/epidemiologia , Homossexualidade Masculina , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças da Boca/etiologia , Infecções por Papillomavirus/complicações , Prevalência , Fatores de RiscoRESUMO
PURPOSE: AIDS-related non-Hodgkin lymphoma (ARL) is the most common cancer in HIV-infected individuals in the United States and other countries in which HIV-positive persons have access to effective combination antiretroviral therapy (cART). Our prior work showed that pretreatment/postdiagnosis plasma levels of some cytokines, such as IL6, IL10, and CXCL13, have the potential to serve as indicators of clinical response to treatment and survival in ARL. The aims of this study were to identify novel prognostic biomarkers for response to treatment and/or survival in persons with ARL, including biomarkers of microbial translocation and inflammation. EXPERIMENTAL DESIGN: We quantified plasma levels of several biomarkers (sCD14, LBP, FABP2, EndoCab IgM, IL18, CCL2/MCP-1, sCD163, IP-10/CXCL10, TARC/CCL17, TNFα, BAFF/BLyS, sTNFRII, sCD44, and sIL2Rα/sCD25) by multiplexed immunometric assays (Luminex) or ELISA in plasma specimens obtained from ARL patients enrolled in the AMC-034 trial, which compared infusional combination chemotherapy (EPOCH: etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone) with concurrent or sequential rituximab. Plasma was collected prior to the initiation of therapy (n = 57) and after treatment initiation (n = 55). RESULTS: We found that several biomarkers decreased significantly after treatment, including TNFα, sCD25, LBP, and TARC (CCL17). Moreover, pretreatment plasma levels of BAFF, sCD14, sTNFRII, and CCL2/MCP-1 were univariately associated with overall survival, and pretreatment levels of BAFF, sTNFRII, and CCL2/MCP-1 were also associated with progression-free survival. CONCLUSIONS: Our results suggest that patients with ARL who responded to therapy had lower pretreatment levels of inflammation and microbial translocation as compared with those who did not respond optimally.
Assuntos
Translocação Bacteriana , Linfoma Relacionado a AIDS/imunologia , Linfoma Relacionado a AIDS/microbiologia , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/microbiologia , Biomarcadores , Humanos , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , PrognósticoRESUMO
BACKGROUND: Women living with HIV (WLWH) experience high rates of anal cancer. Screening using anal cytology, high-resolution anoscopy (HRA) with biopsies, can histologically diagnose anal cancer precursors called high-grade squamous intraepithelial lesions (HSIL). The low specificity of screening using anal cytology results in HRA referral for many WLWH without HSIL. Screening using high-risk human papillomavirus (HR-HPV) may improve specificity. METHODS: Two hundred seven WLWH (63% non-Hispanic black) were screened for anal histologic HSIL (hHSIL) using cytology, HRA-guided biopsies, and Xpert HPV. Xpert performance for predicting anal hHSIL was compared with that of cytology. Usng Xpert 5 HPV genotypic results and accompanying cycle thresholds, receiver operator characteristic curve and recursive partitioning analyses were used to create predictive models for hHSIL. RESULTS: The performance of Xpert to predict hHSIL was not different from that of cytology with a sensitivity (Sn) of 89% and specificity (Sp) of 49%. Interpretation of Xpert was modified using genotypic results and receiver operator characteristic curve analysis, which produced a screen with an Sn and Sp of 75% and 84% for hHSIL, respectively. Another reinterpretation of Xpert was created using recursive partitioning and cycle thresholds, which predicted hHSIL with an Sn and Sp of 75% and 86%, respectively. The detection of HPV-16 was highly predictive of hHSIL in all analyses. These modified screening tests would reduce HRA referral in this population by almost half compared with anal cytology. CONCLUSIONS: Xpert HPV is an alternative to anal cytology to screen for anal HSIL and can be optimized to reduce the number of unnecessary HRAs performed in WLWH.
Assuntos
Infecções por HIV/complicações , HIV-1 , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Lesões Intraepiteliais Escamosas/virologia , Adulto , Canal Anal/patologia , Feminino , Humanos , Lesões Intraepiteliais Escamosas/diagnósticoRESUMO
BACKGROUND: Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV)-related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied. METHODS: Two hundred and sixty MSMLWH aged 18-26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24. RESULTS: Among 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type-associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18-associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events. CONCLUSIONS: 18-26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type-associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.
Assuntos
Alphapapillomavirus , Neoplasias do Ânus , Infecções por HIV , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Minorias Sexuais e de Gênero , Lesões Intraepiteliais Escamosas , Adolescente , Adulto , Canal Anal , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/prevenção & controle , HIV , Infecções por HIV/complicações , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Prevalência , Comportamento Sexual , Vacinação , Adulto JovemRESUMO
BACKGROUND: Antibodies to programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) may perturb human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) by reversing HIV latency and/or boosting HIV-specific immunity, leading to clearance of infected cells. We tested this hypothesis in a clinical trial of anti-PD-1 alone or in combination with anti-CTLA-4 in people living with HIV (PLWH) and cancer. METHODS: This was a substudy of the AIDS Malignancy Consortium 095 Study. ART-suppressed PLWH with advanced malignancies were assigned to nivolumab (anti-PD-1) with or without ipilimumab (anti-CTLA-4). In samples obtained preinfusion and 1 and 7 days after the first and fourth doses of immune checkpoint blockade (ICB), we quantified cell-associated unspliced (CA-US) HIV RNA and HIV DNA. Plasma HIV RNA was quantified during the first treatment cycle. Quantitative viral outgrowth assay (QVOA) to estimate the frequency of replication-competent HIV was performed before and after ICB for participants with samples available. RESULTS: Of 40 participants, 33 received nivolumab and 7 nivolumab plus ipilimumab. Whereas CA-US HIV RNA did not change with nivolumab monotherapy, we detected a median 1.44-fold increase (interquartile range, 1.16-1.89) after the first dose of nivolumab and ipilimumab combination therapy (P = .031). There was no decrease in the frequency of cells containing replication-competent HIV, but in the 2 individuals on combination ICB for whom we had longitudinal QVOA, we detected decreases of 97% and 64% compared to baseline. CONCLUSIONS: Anti-PD-1 alone showed no effect on HIV latency or the latent HIV reservoir, but the combination of anti-PD-1 and anti-CTL-4 induced a modest increase in CA-US HIV RNA and may potentially eliminate cells containing replication-competent HIV. CLINICAL TRIALS REGISTRATION: NCT02408861.
Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , HIV-1 , Neoplasias , Antígeno CTLA-4 , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Receptor de Morte Celular Programada 1 , Latência ViralRESUMO
BACKGROUND: Human papillomavirus (HPV)-associated cervical cancer is a leading cause of death among Indian women. Indian women living with HIV (WLWH) may be at especially high risk. The quadrivalent HPV (qHPV) vaccine is effective in prevention of initial infection with HPV-6/11/16/18 in HIV-negative women. Little is known about previous exposure to HPV-6/11/16/18, safety, and immunogenicity of qHPV in Indian WLWH. METHODOLOGY: One hundred fifty WLWH with different CD4 levels and HIV viral load (VL) were vaccinated at 0/2/6 months at CART-CRS-IDMC, Chennai, India. Serology was performed at weeks 0, 28, and 52 for HPV-6/11/16/18 using a competitive Luminex immunoassay and for HPV-16/18 using a pseudovirion-based neutralization assay. RESULTS: Mean age was 30.8 years (range, 19-44 years). 71/87/73/81% of women were naive (sero-negative and DNA-negative) to HPV-6/11/16/18 at baseline, respectively. Among per-protocol women naive to HPV-6/11/16/18 at baseline, 100/99/99/90%, respectively, seroconverted at week 28 and 95/96/98/71% were sero-positive at week 52, respectively. Pseudovirion-based neutralization assay identified more seroconversion to HPV-18 than competitive Luminex immunoassay. There were no significant differences in the proportion seroconverting by baseline or nadir CD4 or HIV VL; however, there was a trend for increased proportion seroconverting to HPV-18 among women with higher baseline CD4 level (P = 0.052). There were no qHPV-related serious adverse events and no change in CD4 level or HIV VL among women on ART. CONCLUSIONS: qHPV vaccine was safe and immunogenic in Indian WLWH. A high proportion were naive to HPV-6/11/16/18 and may benefit from vaccination although many were married and several years post-initiation of sexual activity.
Assuntos
Anticorpos Antivirais/sangue , Infecções por HIV/tratamento farmacológico , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/efeitos adversos , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Infecções por Papillomavirus/prevenção & controle , Adulto , Feminino , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Humanos , Índia , Infecções por Papillomavirus/virologia , Projetos Piloto , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação , Carga Viral/imunologia , Adulto JovemRESUMO
RATIONALE AND OBJECTIVES: The purpose of this study is to analyze the significance of specific factors in choosing radiology as a specialty compared to switching to/from a different specialty as reported in the Graduation Questionnaire (GQ) and Matriculating Student Questionnaire (MSQ) data provided by Association of American Medical Colleges. METHOD AND MATERIALS: The study cohort included students who completed both the MSQ and GQ questionnaires in the span of 3-5 years. The cohort was divided into three groups-"Committed" (students who chose radiology in both the first and final year of medical school), "Switched Away" (students who chose radiology on the MSQ but later switched to a different specialty, and "Switched-To" (students who chose radiology on GQ after initially selecting an alternate specialty on the MSQ). RESULTS: Of 1965 students who chose radiology between the years 2013 and 2016, 281 were Committed, 625 Switched-Away, and 1059 Switched-To. There were significant differences among the groups for salary, length of residency, and work-life balance factors. In the Switched-Away group, more students were influenced by length of residency (18% vs. 5%, p < 0.001) and fewer were influenced by salary (21% vs. 30%, p=0.004) or work-life balance (54% vs. 66%, pâ¯=â¯0.001) when compared to the Committed group. The Switched-To group did not significantly differ from the Committed group (all p > 0.05) for length of residency (6% vs. 5%), salary (30% vs. 30%) and work-life balance (69% vs. 66%). CONCLUSION: The data provide insight into factors that influence medical students to initially commit to, switch away from, and switch to radiology during medical school. Understanding these dynamics can inform mentors to guide medical students who are interested in a radiology career.
Assuntos
Educação Médica , Internato e Residência , Radiologia , Estudantes de Medicina , Escolha da Profissão , Humanos , Faculdades de Medicina , Inquéritos e QuestionáriosRESUMO
PURPOSE: To evaluate the effectiveness of an evidence-based 12-week Tai Chi course designed to improve balance and physical function in a population of older veterans. METHODS: Community dwelling veterans of all ages with gait and balance problems were invited to participate in the Tai Chi program. Participants completed the Berg Balance Scale (BBS), the Timed Up and Go (TUG) test, and the Falls Efficacy Scale-International (FES-I) at baseline and again at the end of the program. Descriptive statistics were used to summarize study participants' characteristics. The change from baseline to the end of the 12-week program was calculated for each of the three primary outcome variables (BBS, TUG, FES-I). RESULTS: Twenty-two veterans, aged 58 years and above, with perceived gait and/or balance issues were enrolled in the program with completion by 11 veterans. Veterans who completed their final assessments showed the BBS, improved significantly (p = 0.004) from baseline to the 12-week assessment. The TUG scores improved by a median of 1.3 s (p = 0.022). There was not a significant change in the FES-I. CONCLUSIONS: Preliminary findings provide evidence of the effectiveness of a 12-week Tai Chi program to improve functional outcomes for older veterans with mild to moderate gait and balance problems.
Assuntos
Tai Chi Chuan , Veteranos , Acidentes por Quedas/prevenção & controle , Humanos , Pacientes Ambulatoriais , Equilíbrio PosturalRESUMO
BACKGROUND: We aimed to determine if treatment of male sexual partners of women with recurrent bacterial vaginosis (BV) with oral metronidazole 2×/day for 7 days (ie, multidose metronidazole) significantly decreased BV recurrence rates in the female. METHODS: This was a multicenter, 2-arm, double-blind, placebo-controlled study. Women with recurrent BV and current diagnosis of BV by Amsel and Nugent were enrolled. Multidose metronidazole for 7 days was dispensed to women. Male partners were randomized to placebo versus multidose metronidazole for 7 days and asked to refrain from unprotected sex for 14 days. Female follow-up visits were conducted at day 21 and 8 and 16 weeks. Male follow-up visits occurred at days 14-21. BV cure was defined as 0-2 Amsel criteria and Nugent score 0-6 in the female partner with the primary endpoint at 16 weeks. RESULTS: 214 couples were enrolled. In the intent-to-treat population, there was no significant difference between treatment arms for the primary outcome. BV treatment failure occurred in 81% and 80% of women in the metronidazole and placebo arms through the third follow-up visit, respectively (Pâ >â .999). However, women whose male partners adhered to study medication were less likely to fail treatment (adjusted relative risk, .85; 95% CI, .73-.99; Pâ =â .035). This finding persisted in post hoc comparisons in the metronidazole arm. CONCLUSIONS: Overall, this study did not find that male partner treatment with multidose metronidazole significantly reduces BV recurrence in female partners, although women whose partners adhered to multidose metronidazole were less likely to fail treatment. CLINICAL TRIALS REGISTRATION: (NCT02209519).