Effectiveness of JYNNEOS Vaccine Against Diagnosed Mpox Infection - New York, 2022.

In 2022, an international Monkeypox virus outbreak, characterized by transmission primarily through sexual contact among gay, bisexual, and other men who have sex with men (MSM), resulted in 375 monkeypox (mpox) cases in the state of New York outside of New York City (NYC).*,† The JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), licensed by the U.S. Food and Drug Administration (FDA) against mpox as a 2-dose series, with doses administered 4 weeks apart,§ was deployed in a national vaccination campaign.¶ Before this outbreak, evidence to support vaccine effectiveness (VE) against mpox was based on human immunologic and animal challenge studies (1-3). New York State Department of Health (NYSDOH) conducted a case-control study to estimate JYNNEOS VE against diagnosed mpox in New York residents outside of NYC, using data from systematic surveillance reporting. A case-patient was defined as a man aged ≥18 years who received a diagnosis of mpox during July 24-October 31, 2022. Contemporaneous control patients were men aged ≥18 years with diagnosed rectal gonorrhea or primary syphilis and a history of male-to-male sexual contact, without mpox. Case-patients and control patients were matched to records in state immunization systems. JYNNEOS VE was estimated as 1 - odds ratio (OR) x 100, and JYNNEOS vaccination status (vaccinated versus unvaccinated) at the time of diagnosis was compared, using conditional logistic regression models that adjusted for week of diagnosis, region, patient age, and patient race and ethnicity. Among 252 eligible mpox case-patients and 255 control patients, the adjusted VE of 1 dose (received ≥14 days earlier) or 2 doses combined was 75.7% (95% CI = 48.5%-88.5%); the VE for 1 dose was 68.1% (95% CI = 24.9%-86.5%) and for 2 doses was 88.5% (95% CI = 44.1%-97.6%). These findings support recommended 2-dose JYNNEOS vaccination consistent with CDC and NYSDOH guidance.

Assessing the Impact of a PrEP Aware Week Campaign on PrEP Prescription Fills in NYS.

CONTEXT: The New York State (NYS) Department of Health AIDS Institute engaged stakeholders across NYS to participate in the state's first "PrEP Aware Week" (PAW). PAW sought to increase the knowledge, interest, and number of PrEP (pre-exposure prophylaxis) prescriptions filled across NYS. PAW activities were designed to be easy to implement, with minimal cost. Stakeholders were provided activities to implement, along with a social media tool kit featuring videos, graphic ads, and sample social media posts in English and Spanish to use as is or modify. PAW included more than 750 distinct events and activities undertaken by more than 250 participating providers. OBJECTIVE: To assess the impact of PAW on PrEP prescription filling patterns in NYS. DESIGN: An interrupted time-series analysis was conducted to estimate the impact of PAW on overall and new PrEP prescription filling patterns. Separate models were developed by sex (male, female), race and ethnicity (White non-Hispanic, Black non-Hispanic, Hispanic, other, unknown), and region (New York City, rest of NYS). SETTING: PAW took place across NYS during the week beginning October 20, 2019. PARTICIPANTS: PAW was undertaken by more than 250 health care providers, nonmedical health & human services providers, local and state health department staff, and colleges and universities. MAIN OUTCOME MEASURES: The number of overall and new PrEP prescriptions. RESULTS: PAW was associated with modest increases (6%-9%) in the number of PrEP prescription fills in NYS. The PAW impact lasted for about 2 months, generated an estimated 2727 additional PrEP prescription fills statewide, and was realized across sex, region, and racial and ethnic subgroups. Increased prescription fills were driven by those previously prescribed PrEP. Increases in new prescriptions were noted among Latinx individuals (21% increase, 55 additional prescriptions) but not overall or across other groups. CONCLUSION: NYS's PAW was effective at increasing PrEP prescription refills in NYS.

Factors associated with SARS-CoV-2-related hospital outcomes among and between persons living with and without diagnosed HIV infection in New York State.

BACKGROUND: Persons living with diagnosed HIV (PLWDH) are at increased risk for severe illness due to COVID-19. The degree to which this due to HIV infection, comorbidities, or other factors remains unclear. METHODS: We conducted a retrospective matched cohort study of individuals hospitalized with COVID-19 in New York State between March and June 2020, during the first wave of the pandemic, to compare outcomes among 853 PLWDH and 1,621 persons without diagnosed HIV (controls). We reviewed medical records to compare sociodemographic and clinical characteristics at admission, comorbidities, and clinical outcomes between PLWDH and controls. HIV-related characteristics were evaluated among PLWDH. RESULTS: PLWDH were significantly more likely to have cardiovascular (matched prevalence-ratio [mPR], 1.22 [95% CI, 1.07-1.40]), chronic liver (mPR, 6.71 [95% CI, 4.75-9.48]), chronic lung (mPR, 1.76 [95% CI, 1.40-2.21]), and renal diseases (mPR, 1.77 [95% CI, 1.50-2.09]). PLWDH were less likely to have elevated inflammatory markers upon hospitalization. Relative to controls, PLWDH were 15% less likely to require mechanical ventilation or extracorporeal membrane oxygenation (ECMO) and 15% less likely to require admission to the intensive care unit. No significant differences were found in in-hospital mortality. PLWDH on tenofovir-containing regimens were significantly less likely to require mechanical ventilation or ECMO (risk-ratio [RR], 0.73 [95% CI, 0.55-0.96]) and to die (RR, 0.74 [95% CI, 0.57-0.96]) than PLWDH on non-tenofovir-containing regimens. CONCLUSIONS: While hospitalized PLWDH and controls had similar likelihood of in-hospital death, chronic disease profiles and degree of inflammation upon hospitalization differed. This may signal different mechanisms leading to severe COVID-19.

Postpartum Mother-To-Child Transmission of HIV in a Breastfeeding Infant.

This article is an examination of MTCT of HIV through breastfeeding in a mother who seroconverted postnatally.

COVID-19 Outcomes Among Persons Living With or Without Diagnosed HIV Infection in New York State.

Importance: New York State has been an epicenter for both the US coronavirus disease 2019 (COVID-19) and HIV/AIDS epidemics. Persons living with diagnosed HIV may be more prone to COVID-19 infection and severe outcomes, yet few studies have assessed this possibility at a population level. Objective: To evaluate the association between HIV diagnosis and COVID-19 diagnosis, hospitalization, and in-hospital death in New York State. Design, Setting, and Participants: This cohort study, conducted in New York State, including New York City, between March 1 and June 15, 2020, matched data from HIV surveillance, COVID-19 laboratory-confirmed diagnoses, and hospitalization databases to provide a full population-level comparison of COVID-19 outcomes between persons living with diagnosed HIV and persons living without diagnosed HIV. Exposures: Diagnosis of HIV infection through December 31, 2019. Main Outcomes and Measures: The main outcomes were COVID-19 diagnosis, hospitalization, and in-hospital death. COVID-19 diagnoses, hospitalizations, and in-hospital death rates comparing persons living with diagnosed HIV with persons living without dianosed HIV were computed, with unadjusted rate ratios and indirect standardized rate ratios (sRR), adjusting for sex, age, and region. Adjusted rate ratios (aRRs) for outcomes specific to persons living with diagnosed HIV were assessed by age, sex, region, race/ethnicity, transmission risk, and CD4+ T-cell count-defined HIV disease stage, using Poisson regression models. Results: A total of 2988 persons living with diagnosed HIV (2109 men [70.6%]; 2409 living in New York City [80.6%]; mean [SD] age, 54.0 [13.3] years) received a diagnosis of COVID-19. Of these persons living with diagnosed HIV, 896 were hospitalized and 207 died in the hospital through June 15, 2020. After standardization, persons living with diagnosed HIV and persons living without diagnosed HIV had similar diagnosis rates (sRR, 0.94 [95% CI, 0.91-0.97]), but persons living with diagnosed HIV were hospitalized more than persons living without diagnosed HIV, per population (sRR, 1.38 [95% CI, 1.29-1.47]) and among those diagnosed (sRR, 1.47 [95% CI, 1.37-1.56]). Elevated mortality among persons living with diagnosed HIV was observed per population (sRR, 1.23 [95% CI, 1.07-1.40]) and among those diagnosed (sRR, 1.30 [95% CI, 1.13-1.48]) but not among those hospitalized (sRR, 0.96 [95% CI, 0.83-1.09]). Among persons living with diagnosed HIV, non-Hispanic Black individuals (aRR, 1.59 [95% CI, 1.40-1.81]) and Hispanic individuals (aRR, 2.08 [95% CI, 1.83-2.37]) were more likely to receive a diagnosis of COVID-19 than White individuals, but they were not more likely to be hospitalized once they received a diagnosis or to die once hospitalized. Hospitalization risk increased with disease progression to HIV stage 2 (aRR, 1.29 [95% CI, 1.11-1.49]) and stage 3 (aRR, 1.69 [95% CI, 1.38-2.07]) relative to stage 1. Conclusions and Relevance: In this cohort study, persons living with diagnosed HIV experienced poorer COVID-related outcomes relative to persons living without diagnosed HIV; Previous HIV diagnosis was associated with higher rates of severe disease requiring hospitalization, and hospitalization risk increased with progression of HIV disease stage.

Elevated COVID-19 outcomes among persons living with diagnosed HIV infection in New York State: Results from a population-level match of HIV, COVID-19, and hospitalization databases.

BACKGROUND: New York State (NYS) has been an epicenter for both COVID-19 and HIV/AIDS epidemics. Persons Living with diagnosed HIV (PLWDH) may be more prone to COVID-19 infection and severe outcomes, yet few population-based studies have assessed the extent to which PLWDH are diagnosed, hospitalized, and have died with COVID-19, relative to non-PLWDH. METHODS: NYS HIV surveillance, COVID-19 laboratory confirmed diagnoses, and hospitalization databases were matched. COVID-19 diagnoses, hospitalization, and in-hospital death rates comparing PLWDH to non-PLWDH were computed, with unadjusted rate ratios (RR) and indirect standardized RR (sRR), adjusting for sex, age, and region. Adjusted RR (aRR) for outcomes among PLWDH were assessed by age/CD4-defined HIV disease stage, and viral load suppression, using Poisson regression models. RESULTS: From March 1-June 7, 2020, PLWDH were more frequently diagnosed with COVID-19 than non-PLWDH in unadjusted (RR [95% confidence interval (CI)]: 1.43[1.38-1.48), 2,988 PLWDH], but not in adjusted comparisons (sRR [95% CI]: 0.94[0.91-0.97]). Per-population COVID-19 hospitalization was higher among PLWDH (RR [95% CI]: 2.61[2.45-2.79], sRR [95% CI]: 1.38[1.29-1.47], 896 PLWDH), as was in-hospital death (RR [95% CI]: 2.55[2.22-2.93], sRR [95%CI]: 1.23 [1.07-1.40], 207 PLWDH), albeit not among those hospitalized (sRR [95% CI]: 0.96[0.83-1.09]). Among PLWDH, hospitalization risk increased with disease progression from HIV Stage 1 to Stage 2 (aRR [95% CI]:1.27[1.09-1.47]) and Stage 3 (aRR [95% CI]: 1.54[1.24-1.91]), and for those virally unsuppressed (aRR [95% CI]: 1.54[1.24-1.91]). CONCLUSION: PLWDH experienced poorer COVID-related outcomes relative to non-PLWDH, with 1-in-522 PLWDH dying with COVID-19, seemingly driven by higher rates of severe disease requiring hospitalization.

Investigation of Presumptive HIV Transmission Associated with Hospitalization Using Nucleotide Sequence Analysis - New York, 2017.

Since implementation of Standard Precautions* for the prevention of bloodborne pathogen transmission in 1985, health care-associated transmission of human immunodeficiency virus (HIV) in the United States has been rare (1). In October 2017, the New York City Department of Health and Mental Hygiene (NYCDOHMH) and the New York State Department of Health (NYSDOH) were notified by a clinician of a diagnosis of acute HIV infection in a young adult male (patient A) without recognized risk factors (i.e., he was monogamous, had an HIV-negative partner, and had no injection drug use) who had recently been hospitalized for a chronic medical condition. The low risk coupled with the recent hospitalization and medical procedures prompted NYSDOH, NYCDOHMH, and CDC to investigate this case as possible health care-associated transmission of HIV. Among persons with known HIV infection who had hospitalization dates overlapping those of patient A, one person (patient B) had an HIV strain highly similar to patient A's strain by nucleotide sequence analysis. The sequence relatedness, combined with other investigation findings, indicated a likely health care-associated transmission. Nucleotide sequence analysis, which is increasingly used for detecting HIV clusters (i.e., persons with closely related HIV strains) and to inform public health response (2,3), might also be used to identify possible health care-associated transmission of HIV to someone with health care exposure and no known HIV risk factors (4).

Evaluation of Algorithms Used for PrEP Surveillance Using a Reference Population From New York City, July 2016-June 2018.

OBJECTIVE: Daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) use as HIV preexposure prophylaxis (PrEP) is monitored by identifying TDF/FTC prescriptions from pharmacy databases and applying diagnosis codes and antiretroviral data to algorithms that exclude TDF/FTC prescribed for HIV postexposure prophylaxis (PEP), HIV treatment, and hepatitis B virus (HBV) treatment. We evaluated the accuracy of 3 algorithms used by the Centers for Disease Control and Prevention (CDC), Gilead Sciences, and the New York State Department of Health (NYSDOH) using a reference population in Bronx, New York. METHODS: We extracted diagnosis codes and data on all antiretroviral prescriptions other than TDF/FTC from an electronic health record database for persons aged ≥16 prescribed TDF/FTC during July 2016-June 2018 at Montefiore Medical Center. We reviewed medical records to classify the true indication of first TDF/FTC use as PrEP, PEP, HIV treatment, or HBV treatment. We applied each algorithm to the reference population and compared the results with the medical record review. RESULTS: Of 2862 patients included in the analysis, 694 used PrEP, 748 used PEP, 1407 received HIV treatment, and 13 received HBV treatment. The algorithms had high specificity (range: 98.4%-99.0%), but the sensitivity of the CDC algorithm using a PEP definition of TDF/FTC prescriptions ≤30 days was lower (80.3%) than the sensitivity of the algorithms developed by Gilead Sciences (94.7%) or NYSDOH (96.1%). Defining PEP as TDF/FTC prescriptions ≤28 days improved CDC algorithm performance (sensitivity, 95.8%; specificity, 98.8%). CONCLUSIONS: Adopting the definition of PEP as ≤28 days of TDF/FTC in the CDC algorithm should improve the accuracy of national PrEP surveillance.

Notes from the Field: Increase in Reported Hepatitis A Infections Among Men Who Have Sex with Men - New York City, January-August 2017.

Since 2011, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) has typically been notified of three or fewer cases of hepatitis A virus (HAV) infection each year among men who have sex with men (MSM) who reported no travel to countries where HAV is endemic. This year, DOHMH noted an increase in HAV infections among MSM with onsets in January-March 2017, and notified other public health jurisdictions via Epi-X, CDC's communication exchange network. As a result, 51 patients with HAV infection involving MSM were linked to the increase in NYC.

Prevalencia de infección anal por el virus del papiloma humano en el Hospital Comandante Manuel Fajardo / Prevalence of HPV anal infection at Comandante Manuel Fajardo Hospital

Introducción: la infección anal por el virus del papiloma humano, se ha convertido en una entidad muy frecuente y se ha demostrado su relación con el cáncer anal. Objetivo: estimar la prevalencia del virus del papiloma humano en pacientes atendidos en el servicio de coloproctología del Hospital Comandante Manuel Fajardo. Métodos: se realizó estudio observacional descriptivo y transversal en 102 pacientes sin patologías agudas anorrectales que dieron su consentimiento. El estudio se realizó desde enero de 2010 hasta diciembre 2013. Se aplicó entrevista a los pacientes, recogida de datos de historia clínica, examen físico anogenital y examen citológico anal. Las variables de estudio fueron: edad, color de la piel, estado civil, nivel escolar y factores de riesgo. Resultados: de 102 citologías realizadas, 29, (25,66 por ciento) fueron positivas a la infección anal por el virus del papiloma humano. La prevalencia de citologías positivas a la infección anal por el virus del papiloma humano según variables fue: sexo femenino: 57 (55,80 por ciento); edades entre 18 y 40 años; mestizos (35 por ciento); divorciados (55,55 por ciento); pacientes con nivel primario; portadores al VIH (73,07 por ciento). Conclusiones: la citología anal constituyó un procedimiento factible para la detección de la incidencia por la infección anal por el virus del papiloma humano y los factores de riesgo son similares a los encontrados en otras regiones y publicaciones(AU)

Introduction: Human papillomavirus anal infection has become a very common entity and been proved its relationship with anal cancer. Objective: To estimate the prevalence of HPV in patients treated by the coloproctology service at Manuel Fajardo Hospital. Methods: A observational, descriptive and cross-sectional study with 102 patients without any acute anorectal pathologies, and who gave their informed consent. The studied was conducted from January 2010 to December 2013. The patients were interviewed, clinical record data were gathered, anal-genital physical examination and anal-cytological examination were performed. The study variables were age, skin color, marital status, educational level and risk factors. Results: Out of 102 smear tests performed, 29 (25.66 por ciento) were Human papillomavirus anal infection-positive. The prevalence of Human papillomavirus anal infection-positive smears according to variables were: female sex (57, 55.80 por ciento), aged 18-40; mestizos (35 por ciento); divorced (55.55 por ciento); primary education patients; HIV-carriers (73.07 por ciento). Conclusions: Anal cytology was an effective procedure for detecting the incidence of HPVAI, and the risk factors are similar to those found in other regions and publications(AU)

Prevalencia de infección anal por el virus del papiloma humano en el Hospital Comandante Manuel Fajardo / Prevalence of HPV anal infection at Comandante Manuel Fajardo Hospital

Introducción: la infección anal por el virus del papiloma humano, se ha convertido en una entidad muy frecuente y se ha demostrado su relación con el cáncer anal. Objetivo: estimar la prevalencia del virus del papiloma humano en pacientes atendidos en el servicio de coloproctología del Hospital Comandante Manuel Fajardo. Métodos: se realizó estudio observacional descriptivo y transversal en 102 pacientes sin patologías agudas anorrectales que dieron su consentimiento. El estudio se realizó desde enero de 2010 hasta diciembre 2013. Se aplicó entrevista a los pacientes, recogida de datos de historia clínica, examen físico anogenital y examen citológico anal. Las variables de estudio fueron: edad, color de la piel, estado civil, nivel escolar y factores de riesgo. Resultados: de 102 citologías realizadas, 29, (25,66 por ciento) fueron positivas a la infección anal por el virus del papiloma humano. La prevalencia de citologías positivas a la infección anal por el virus del papiloma humano según variables fue: sexo femenino: 57 (55,80 por ciento); edades entre 18 y 40 años; mestizos (35 por ciento); divorciados (55,55 por ciento); pacientes con nivel primario; portadores al VIH (73,07 por ciento). Conclusiones: la citología anal constituyó un procedimiento factible para la detección de la incidencia por la infección anal por el virus del papiloma humano y los factores de riesgo son similares a los encontrados en otras regiones y publicaciones(AU)

Introduction: Human papillomavirus anal infection has become a very common entity and been proved its relationship with anal cancer. Objective: To estimate the prevalence of HPV in patients treated by the coloproctology service at Manuel Fajardo Hospital. Methods: A observational, descriptive and cross-sectional study with 102 patients without any acute anorectal pathologies, and who gave their informed consent. The studied was conducted from January 2010 to December 2013. The patients were interviewed, clinical record data were gathered, anal-genital physical examination and anal-cytological examination were performed. The study variables were age, skin color, marital status, educational level and risk factors. Results: Out of 102 smear tests performed, 29 (25.66 por ciento) were Human papillomavirus anal infection-positive. The prevalence of Human papillomavirus anal infection-positive smears according to variables were: female sex (57, 55.80 por ciento), aged 18-40; mestizos (35 por ciento); divorced (55.55 por ciento); primary education patients; HIV-carriers (73.07 por ciento). Conclusions: Anal cytology was an effective procedure for detecting the incidence of HPVAI, and the risk factors are similar to those found in other regions and publications(AU)

Using computer-based monitoring and intervention to prevent harmful combinations of antiretroviral drugs in the New York State AIDS Drug Assistance Program.

BACKGROUND: Despite the growing number of HIV-infected people and the acknowledged complexity of HIV therapy, there are no standard safeguards in the outpatient setting against dangerous antiretroviral (ARV) therapy combinations in the publicly financed arena. METHODS: Using quarterly pharmacy claims data from the New York State AIDS Drug Assistance Program, a three-phase approach was developed: The extent of contraindicated ARV combinations was ascertained; prescriber alerts were developed; and, finally, the reimbursement of contraindicated ARV combinations was blocked at pharmacy. ARV dosages, the number of ARV medications in a regimen, clinical adequacy of the regimen, medication claim denials, clinician adjudication, and subsequent clinician prescribing patterns were analyzed. RESULTS: For the 27-month study period (October 1, 2006-December 31, 2009), 112,383 ARV regimens involving 396,303 ARV medications for 25,463 unique recipients were individually analyzed. A total of 1,089 interventions occurred; denials and interventions increased per quarter from a baseline of 129 to 217 by the study's end. All contraindicated combinations referred for adjudication during the study were upheld. More than 88.3% (range, 87.1% to 89.9%) of regimens per quarter were consistent with effective ARV as promulgated by current guidelines. The targeted dissemination of ARV drug interaction safety alerts to previous prescribers of contraindicated combinations during the first year of the review curtailed the practice by 77.3%. CONCLUSION: A systems-level intervention can be used on a state level to reduce ARV contraindicated medication errors in the outpatient setting through a coordinated approach of prescriber clinical education and electronic pharmacy and billing systems and provides an effective safety and quality monitoring model.

Long-term efficacy and safety of the HIV integrase inhibitor raltegravir in patients with limited treatment options in a Phase II study.

BACKGROUND: Raltegravir in combination therapy has demonstrated potent suppression of HIV-1 with a favorable safety profile. This report provides 96-week efficacy and safety data from Protocol 005, a Phase II study. METHODS: HIV-infected patients with very limited treatment options and failing antiretroviral therapy were randomized to raltegravir 200, 400, or 600 mg or placebo b.i.d., plus optimized background therapy for >or=24 weeks; all patients were then offered open-label raltegravir 400 mg b.i.d. Efficacy measurements included changes in viral load and CD4 count from baseline and percent of patients with HIV-1 RNA <400 and <50 copies/mL. RESULTS: One hundred and thirty-three patients received raltegravir and 45 received placebo. No dose-dependent differentiation in the safety or antiviral activity of raltegravir was observed during the double-blind phase. For the combined raltegravir groups, mean change in viral load from baseline was -1.60 log10 copies/mL at week 48 and -1.38 log10 copies/mL at week 96 (observed failure approach). At week 48, HIV-1 RNA levels were <400 copies/mL in 68% of raltegravir recipients and <50 copies/mL in 55%; these levels were maintained in 55% and 48% of raltegravir recipients, respectively, at week 96 (noncompleter = failure). There were few discontinuations of raltegravir (4%) due to adverse events. CONCLUSIONS: In patients with limited treatment options, raltegravir with OBT had a potent and sustained antiretroviral effect and was generally well tolerated through 96 weeks.

A preliminary study of cytokines in suicidal and nonsuicidal adolescents with major depression.

BACKGROUND: Increased systemic cytokine levels, modulators of the immune system, have been repeatedly documented in adult and adolescent major depressive disorder (MDD). This preliminary study extends this work to test the role of cytokines in suicidal symptomatology in adolescent MDD. Hypotheses were that acutely suicidal depressed adolescents would have: (1) increased plasma levels of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1beta, and (2) a proinflammatory/antiinflammatory cytokine imbalance (indexed by plasma IFN-gamma/IL-4), compared to nonsuicidal depressed adolescents and healthy controls. METHODS: Twelve suicidal adolescents with MDD (7 females [58%]; 5 medication-free/naïve), 18 nonsuicidal adolescents with MDD (12 females [67%]; 8 medication-free/naïve), and 15 controls (8 females [53%]) were enrolled. MDD had to be of at least 6 weeks duration, with a minimum severity score of 40 on the Children's Depression Rating Scale-Revised. Plasma cytokines were examined using enzyme-linked immunosorbent assays. Nonparametric tests were used to compare subject groups. RESULTS: Unexpectedly, suicidal adolescents with MDD had significantly decreased plasma TNF-alpha concentrations compared to nonsuicidal adolescents with MDD (1.33 +/- 2.95 pg/mL versus 30.9 +/- 110.9 pg/mL; p = 0.03). IFN-gamma was increased in both suicidal and nonsuicidal adolescents with MDD compared to controls (2.14 +/- 6.22 and 4.20 +/- 14.48 versus 0.37 +/- 0.64; p < 0.02, p = 0.005). Findings remained evident when controlled for age and gender. CONCLUSIONS: Our preliminary findings suggest that immune system dysregulation may be associated with suicidal symptomatology in adolescent MDD. These findings should be replicated in larger samples with medication-free adolescents.

A cytokine study in children and adolescents with Tourette's disorder.

BACKGROUND: While immune system dysregulation has been postulated to play a role in Tourette's disorder (TD), most research has focused on the hypothesis of an autoimmune process similar to rheumatic fever. This study examined the potential role of cytokines, modulators of the immune system. We hypothesized that children with TD would have increased levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-12, IL-1 beta and IL-6, and decreased IL-2. We also explored whether comorbid obsessive compulsive disorder (OCD) had an effect on the cytokine profile of TD patients. METHOD: Thirty-two children and adolescents with TD (27 males, ages 7-18 years), 17 with comorbid OCD (14 males), and 16 healthy comparison subjects (7 males, ages 9-19), were enrolled. Plasma cytokines were examined using an enzyme-linked immunosorbent assay. The Mann-Whitney and binary logistic regression tests were used to compare the groups. RESULTS: Only patients with comorbid OCD (TD+OCD; n=17) had significantly elevated IL-12 plasma levels compared to controls (2.73+/-5.12 pg/ml vs. 0.55+/-0.88 pg/ml, rank statistic=222.5; p<0.04). IL-2 was significantly higher in the TD+OCD subgroup compared to the non-OCD TD subgroup (0.74+/-0.29 pg/ml vs. 0.49+/-0.24 pg/ml, rank statistics=108.5; p<0.03). There were no other significant cytokine differences between groups. CONCLUSIONS: Findings suggest a role for IL-12 and IL-2 in TD, and that the TD+OCD subgroup may involve different neuroimmunological functions than the TD-OCD subgroup. Larger studies with medication-free patients should follow.

Immune system dysregulation in adolescent major depressive disorder.

BACKGROUND: A large body of evidence suggests that immune system dysregulation is associated with Major Depressive Disorder (MDD) in adults. This study extends this work to adolescent MDD to examine the hypotheses of immune system dysregulation in adolescents with MDD, as manifested by significantly: (i) elevated plasma levels of cytokines (interferon [IFN]-gamma, tumor necrosis factor-alpha, interleukin [IL]-6, IL-1beta, and IL-4); and (ii) Th1/Th2 cytokine imbalance shifted toward Th1 as indexed by increased IFN-gamma/IL-4. METHOD: Thirty adolescents with MDD (19 females; 13 medication-free/naïve; ages 12-19) of at least 6 weeks duration and a minimum severity score of 40 on the Children's Depression Rating Scale-Revised, and 15 healthy comparisons (8 females), group-matched for age, were enrolled. Plasma cytokines were examined using enzyme-linked immunosorbent assay. Mann-Whitney test was used to compare subjects with MDD and controls. RESULTS: Adolescents with MDD had significantly elevated plasma IFN-gamma levels (3.38+/-11.8 pg/ml versus 0.37+/-0.64 pg/ml; p<0.003), and IFN-gamma/IL-4 ratio (16.6+/-56.5 versus 1.76+/-2.28; p=0.007). A trend for IL-6 to be elevated in the MDD group was also observed (1.52+/-2.88 pg/ml versus 0.49+/-0.90 pg/ml; p=0.09). Importantly, findings remained evident when medicated subjects were excluded. CONCLUSIONS: Findings suggest that immune system dysregulation may be associated with adolescent MDD, with an imbalance of Th1/Th2 shifted toward Th1, as documented in adult MDD. Larger studies with medication-free adolescents should follow.

Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial.

BACKGROUND: Raltegravir (MK-0518) is an HIV-1 integrase inhibitor with potent in-vitro activity against HIV-1 strains including those resistant to currently available antiretroviral drugs. The aim of this study was to assess the safety and efficacy of raltegravir when added to optimised background regimens in HIV-infected patients. METHODS: HIV-infected patients with HIV-1 RNA viral load over 5000 copies per mL, CD4 cell counts over 50 cells per muL, and documented genotypic and phenotypic resistance to at least one nucleoside reverse transcriptase inhibitor, one non-nucleoside reverse transcriptase inhibitor, and one protease inhibitor were randomly assigned to receive raltegravir (200 mg, 400 mg, or 600 mg) or placebo orally twice daily in this multicentre, triple-blind, dose-ranging, randomised study. The primary endpoints were change in viral load from baseline at week 24 and safety. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, with the number NCT00105157. FINDINGS: 179 patients were eligible for randomisation. 44 patients were randomly assigned to receive 200 mg raltegravir, 45 to receive 400 mg raltegravir, and 45 to receive 600 mg raltegravir; 45 patients were randomly assigned to receive placebo. One patient in the 200 mg group did not receive treatment and was therefore excluded from the analyses. For all groups, the median duration of previous antiretroviral therapy was 9.9 years (range 0.4-17.3 years) and the mean baseline viral load was 4.7 (SD 0.5) log10 copies per mL. Four patients discontinued due to adverse experiences, three (2%) of the 133 patients across all raltegravir groups and one (2%) of the 45 patients on placebo. 41 patients discontinued due to lack of efficacy: 14 (11%) of the 133 patients across all raltegravir groups and 27 (60%) of the 45 patients on placebo. At week 24, mean change in viral load from baseline was -1.80 (95% CI -2.10 to -1.50) log10 copies per mL in the 200 mg group, -1.87 (-2.16 to -1.58) log10 copies per mL in the 400 mg group, -1.84 (-2.10 to -1.58) log10 copies per mL in the 600 mg group, and -0.35 (-0.61 to -0.09) log(10) copies per mL for the placebo group. Raltegravir at all doses showed a safety profile much the same as placebo; there were no dose-related toxicities. INTERPRETATION: In patients with few remaining treatment options, raltegravir at all doses studied provided better viral suppression than placebo when added to an optimised background regimen. The safety profile of raltegravir is comparable with that of placebo at all doses studied.

Daily low-dose subcutaneous interleukin-2 added to single- or dual-nucleoside therapy in HIV infection does not protect against CD4+ T-cell decline or improve other indices of immune function: results of a randomized controlled clinical trial (ACTG 248).

CONTEXT: Approaches to preserve or enhance immune function in HIV-1 infection are needed. OBJECTIVES: To examine the ability of daily low-dose interleukin-2 (IL-2) in combination with antiretroviral therapy to preserve circulating CD4+ T-cell counts, the clinical safety and tolerability of this treatment, and safety with respect to changes in plasma HIV-1 RNA levels. DESIGN: Twenty-four-week, phase 2, multicenter, randomized, open-label trial conducted at 12 AIDS Clinical Trials Units between September 1995 and May 1997. PARTICIPANTS: A total of 115 HIV-infected persons with screening CD4+ T-cell counts between 300 and 700 cells/mm who were on stable single- or dual-nucleoside therapy for at least 2 months, 11% of whom were also on a protease inhibitor at study entry. INTERVENTIONS: Patients were randomly assigned to receive IL-2 at a dose of 1 million IU subcutaneously once daily plus continued anti-retroviral therapy (ART + IL-2, n = 57) vs. continued ART alone (ART alone, n = 58). IL-2 dose reductions were made for objective or subjective toxicities. All subjects randomly assigned to the IL-2 arm who interrupted ART were also required to discontinue IL-2 for the same period. MAIN OUTCOME MEASURES: The primary endpoint was a decrease in CD4 T-cell count from baseline; the safety analysis was based on change in plasma HIV RNA by bDNA; and clinical safety and tolerability were analyzed by standard clinical criteria. RESULTS: Of the patients with a baseline CD4 T-cell count recorded, 15 (27%) of 55 patients randomly assigned to ART alone had a drop of > or =25% in their CD4 T-cell count and 23 (41%) of 56 patients randomly assigned to ART + IL-2 had a drop of > or =25% in their CD4 T-cell count at some time over the 24 weeks of the study. This difference was not statistically significant. There was a statistically significant greater variance in CD4 T-cell counts in the IL-2-treated group. More patients in the IL-2 group had at least a 25% increase in CD4 T-cell counts over baseline (34 vs. 13%, P = 0.007). A comparison of grade 3 or worse toxicity showed no differences between the arms, but IL-2 was associated with significantly more grade 2 or worse general body symptoms, primarily discomfort and fatigue. There was no significant difference between the groups with regard to changes in plasma HIV RNA, lymphocyte proliferation, natural killer cell activity, skin test responses to recall antigens, or antibody responses to immunization. Plasma markers of immune activation all increased significantly in IL-2 recipients. CONCLUSIONS: In patients with baseline CD4 T-cell counts > or =300 cells/mm primarily treated with single- or dual-nucleoside ART, subcutaneously administered IL-2 at a dose of 1 million IU daily for up to 24 weeks had low toxicity but showed no consistent benefit in preventing decline in CD4 T-cell counts and minimal evidence of immunologic improvement vs. continued ART alone.