Well-controlled HIV Infection Research Articles

Alcohol consumption and neurocognitive deficits in people with well-treated HIV in Switzerland.

BackgroundHazardous alcohol consumption and HIV infection increase the risk of neurocognitive impairment (NCI). We examined the association between alcohol consumption and specific neurocognitive domain function in people with HIV (PWH) taking modern antiretroviral therapy.MethodsThe Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is a prospective, longitudinal, multicentre and multilingual (French, German and Italian) study of patients aged ≥45 years old enrolled in the Swiss HIV Cohort Study (SHCS). Baseline data from 981 study participants were examined. Five neurocognitive domains were evaluated: motor skills, speed of information processing, attention/working memory, executive function and verbal episodic memory. NCI was examined as binary (presence/absence) and continuous (mean z-score) outcomes against Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) scores using logistic and linear regression models, respectively.ResultsMost participants (96.2%) had undetectable viral loads and 64% were aged >50 years old. Hazardous alcohol consumption was observed in 49.4% of participants and binge drinking in 4.2%. While alcohol consumption frequency and quantity were not associated with NCI, the practice of binge drinking was significantly associated with impaired motor skills and overall neurocognitive function in both binary (odds ratio, OR ≥2.0, P <0.05) and continuous (mean z-score difference -0.2 to -0.4, P ≤0.01) outcomes. A significant U-shaped distribution of AUDIT-C score was also observed for motor skills and overall neurocognitive function.ConclusionsIn this cohort of PWH with well-controlled HIV infection, NCI was associated with the practice of binge drinking rather than alcohol consumption frequency or quantity. Longitudinal analysis of alcohol consumption and NCI in this population is currently underway.

711. Rapid, non-invasive detection and monitoring of Bartonella quintana endocarditis by plasma-based next-generation sequencing of microbial cell-free DNA

BackgroundThere are up to 50,000 new cases of infective endocarditis each year in the United States, of which approximately 20% are culture negative endocarditis (CNE). In-hospital mortality remains high at 20 to 30%. Despite advances in diagnostic testing, determining the timing of surgery and duration of treatment in CNE are significant challenges for clinicians. Plasma next-generation sequencing (NGS) for circulating microbial cell-free DNA (mcfDNA) has shown utility in diagnosing and monitoring the response to treatment in endocarditis.MethodsSerial blood samples were obtained prior to and after aortic valve replacement in a patient with culture negative endocarditis. Microbial cfDNA was extracted from plasma and NGS was performed by Karius, Inc. (Redwood City, California). Human sequences were removed and remaining sequences were aligned to a curated database of over 1,400 pathogens. Organisms present above a predefined statistical significance threshold were reported and quantified in DNA molecules per microliter (MPM). Chart review was performed for clinical correlation.ResultsA 53-year old man with history of homelessness, well-controlled HIV infection and a bioprosthetic aortic valve presented with symptomatic severe aortic stenosis and elevated inflammatory markers 3 years following valve surgery. Transesophageal echocardiography showed a paravalvular leak. Bartonella quintana was detected by Karius NGS (in parallel Bartonella henselae serologies were positive). After 4 weeks of parenteral antibiotics, repeat Karius testing demonstrated a 94% (16-fold) decrease in the Bartonella quintana mcfDNA signal to 8813 MPM. He underwent surgical valve replacement; twenty-four hours after removal of the infected valve repeat Karius testing showed a rapid decay of the Bartonella quintana mcfDNA signal to 103 MPM. The patient completed 3 months of oral antibiotics post-operatively, ultimately returning to his former performance status.ConclusionPlasma-based next-generation sequencing assays for circulating microbial cell-free DNA offer a unique means of pathogen detection, assessment of infection burden and monitoring of response to both medical treatment and surgical debridement/definitive source control in a case of Bartonella quintana endocarditis.DisclosuresAsim A. Ahmed, MD, Karius (Employee)

What Might Surviving Coronavirus Disease 2019 Look Like for People Living with HIV?

What Might Surviving Coronavirus Disease 2019 Look Like for People Living with HIV?

Gastrointestinal mucormycosis due to Rhizopus microsporus following Streptococcus pyogenes toxic shock syndrome in an HIV patient: a case report

BackgroundGastrointestinal (GI) mucormycosis is a rare and often deadly form of mucormycosis. Delayed diagnosis can lead to an increased risk of death. Here, we report a case of GI mucormycosis following streptococcal toxic shock syndrome in a virologically suppressed HIV-infected patient.Case presentationA 25-year-old Thai woman with a well-controlled HIV infection and Grave’s disease was admitted to a private hospital with a high-grade fever, vomiting, abdominal pain, and multiple episodes of mucous diarrhea for 3 days. On day 3 of that admission, the patient developed multiorgan failure and multiple hemorrhagic blebs were observed on all extremities. A diagnosis of streptococcal toxic shock was made before referral to Siriraj Hospital – Thailand’s largest national tertiary referral center. On day 10 of her admission at our center, she developed feeding intolerance and bloody diarrhea due to bowel ischemia and perforation. Bowel resection was performed, and histopathologic analysis of the resected bowel revealed acute suppurative transmural necrosis and vascular invasion with numerous broad irregular branching non-septate hyphae, both of which are consistent with GI mucormycosis. Peritoneal fluid fungal culture grew a grayish cottony colony of large non-septate hyphae and spherical sporangia containing ovoidal sporangiospores. A complete ITS1–5.8S-ITS2 region DNA sequence analysis revealed 100% homology with Rhizopus microsporus strains in GenBank (GenBank accession numbers KU729104 and AY803934). As a result, she was treated with liposomal amphotericin B. However and in spite of receiving appropriate treatment, our patient developed recurrent massive upper GI bleeding from Dieulafoy’s lesion and succumbed to her disease on day 33 of her admission.ConclusionDiagnosis of gastrointestinal mucormycosis can be delayed due to a lack of well-established predisposing factors and non-specific presenting symptoms. Further studies in risk factors for abdominal mucormycosis are needed.

HIV-positive deceased donor-to-HIV-positive recipient kidney transplantation: The HOPE must go on.

Nowadays, HIV infection is a chronic disease, this is due to the efficacy of antiretroviral therapy (ART) in the control of viral replication. The prevalence of chronic kidney disease (CKD) among those well-controlled HIV positive (HIV+) patients is higher than in the general population and kidney transplantation has been established as the best therapeutic option for HIV+ patients with end-stage renal disease. However, this population has lower access to transplantation.

Rituximab for Lupus-Like Membranous Nephropathy in the Setting of Well-Controlled HIV Infection

1Division of Nephrology, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 2Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY The authors have no conflicts of interest to declare.

COVID-19 Pneumonia in Patients With HIV: A Case Series

To the Editors: As our understanding of the coronavirus disease 2019 (COVID-19) improves through emerging data from the general population affected with COVID-19, there is a paucity of information regarding the management and prognosis of patients with HIV infection who may be at an increased risk for morbidity and mortality.1 Here, we describe our experience with the management of COVID-19 in patients with HIV at a health care facility in Newark, the center of the HIV epidemic of New Jersey.2 We included all patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection defined as a positive result on a reverse transcriptase polymerase chain reaction assay of a specimen collected on a nasopharyngeal swab. We identified 27 patients who had a known history of HIV at the time of presentation. Of these, 51% (n = 14) were managed in the ambulatory setting, whereas the rest were hospitalized. The median age was 58 years, there were 15 men and 12 women, and 93% (n = 25) were black or African Americans. The top 4 common symptoms at presentation were fever (67%), cough (63%), dyspnea (63%), and fatigue (48%), which had started over a median duration of 3 days before presentation. More than half of the patients had a history of systemic hypertension (59%), and about one-third reported diabetes mellitus (33%) or chronic kidney disease (27%) (Table 1).TABLE 1.: Demographic, Clinical Characteristics, and Outcomes of HIV Patients With COVID-19 (n = 27)TABLE 1-A.: Demographic, Clinical Characteristics, and Outcomes of HIV Patients With COVID-19 (n = 27)Ambulatory patients were hemodynamically stable at the time of presentation and demonstrated an oxygen saturation of 94–100% on ambient air. They were discharged home with no medical therapy but with the following recommendations: (1) self-quarantine for at least 2 weeks, (2) return to the emergency department for management in case of new-onset symptoms such as fever and dyspnea, and (3) adherence to antiretroviral therapy. Ambulatory patients were followed up with phone calls through a telemedicine platform over a median duration of 14 days. Patients were hospitalized and managed in the inpatient setting if they (1) had signs of sepsis or septic shock defined by the 2016 Third International Consensus Definitions for Sepsis and Septic Shock3 and (2) reported dyspnea requiring a step up in oxygenation therapy to maintain an oxygen saturation between 88% and 94%. Major laboratory markers and immunological data of their HIV status are given in Table 1. The median lymphocyte count was 17%, with a serum d-dimer and procalcitonin of 1.9 ng/mL and 0.26 μ/L, respectively. Patients reported a median CD4 count of 551, and the viral load was <120 in 96% (n = 26) of the patients. Data on antiretroviral regimen before presentation were unavailable in 15% (n = 4) of the patients. Among those with full data, integrase-based regimen was used in 33% (n = 9), nonnucleoside reverse transcriptase inhibitor (NNRTI) in 19% (n = 7), protease inhibitor (PI) + integrase in 19% (n = 7), NNRTI + integrase in 7% (n = 3), and PI based in only 1 patient. Of the hospitalized patients, 26% (n = 7) received hydroxychloroquine and 30% (n = 6) were managed with empiric antibiotics for suspected community-acquired pneumonia. Antiretroviral therapy was held during hospitalization. None of the patients had a superimposed infection, defined as an isolated organism in a positive sputum, urine, or blood culture. After a median hospital course of 10 days, 3 patients required intensive unit level of care and 2 of them had died. The deceased subjects were elderly patients, with multiple coexisting conditions whose course was complicated by septic shock and multiorgan dysfunction syndrome. There were no cases of hospital admission for patients who were managed in the ambulatory setting. In this series of HIV patients with COVID-19, we found a similarity in presentation with what has been reported for the general population. Half of the patients were managed in the ambulatory setting with no reported mortality or morbidity. In-hospital survival was 85% and 23% required intensive care unit admission. Of note, all 27 patients had well-controlled HIV infection evidenced by elevated CD4 count levels and low viral loads. As the challenge involving the management of COVID-19 evolves, large-scale studies are necessary to better understand the management and prognosis of patients with HIV who present with COVID-19.

Safety and Efficacy of Immune Checkpoint Inhibitors in Patients With Cancer Living With HIV: A Perspective on Recent Progress and Future Needs.

Recent studies have identified durable responses with the use of immune checkpoint inhibitors in patients with mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC). The dramatic improvement in clinical outcomes led to the US Food and Drug Administration approval of pembrolizumab, nivolumab, and nivolumab in combination with ipilimumab in metastatic patients with MSI-H/MMR-D CRC who previously experienced progression on cytotoxic therapies. In the clinical trials investigating these agents, HIV-seropositive patients were not included and therefore the clinical efficacy of these agents in patients with metastatic MSI-H/MMR-D CRC living with HIV is unclear. On the basis of growing evidence, immune checkpoint blockade therapies seem to be a safe approach in patients with well-controlled HIV infection. Research on immunotherapeutic approaches in patients living with HIV and cancer is an area of unmet medical need that can be addressed by clinical trial designs that are inclusive of patients with well-controlled seropositive HIV and trials that specifically evaluate immune therapies in patients living with HIV.

Evaluation of left ventricular systolic function by Myocardial Deformation Imaging in asymptomatic HIV patients

Background and Aims: Despite improvements in clinical care, evidence from both industrialized and developing countries indicates that the prevalence of subclinical cardiac dysfunction in individuals with well-controlled HIV infection may approach 50% and represent a newly recognized comorbid condition. The aim of our study was to reveal abnormalities in cardiac function using conventional transthoracic echocardiography and left ventricular strain imaging in HIV infected patients without cardiovascular disease.&#x0D; Methods: This was a hospital based, single center descriptive cross-sectional comparative study conducted in National Academy of Medical Sciences (NAMS), Bir Hospital which included HIV patients with baseline examination including a patient medical history, clinical examination, baseline CD4 count, viral load and a standardized transthoracic echocardiography and strain imaging examination and the findings were compared among age and sex frequency matched healthy adult population.&#x0D; Results: Our study enrolled 142 patients out of which 95 HIV positive patients (mean age 36.7±9.2 years with 58% female) and 47 healthy control (mean age 33.7±8 years with 57.4% female). The median duration of HIV diagnosis was 7 years (IQR 2, 10) and median CD4 count was 464 cells/mm3 (IQR 259,750). There was no significant difference in conventional echocardiographic parameters between two groups except for transmitral E velocity that was lower in HIV group (P value of 0.001). The HIV population has lower mean global longitudinal strain (GLS) value of -19.92% ± 2.54 SD compared to the healthy control population with mean of -21.39% ± 1.54 SD(P value of 0.001) and patients with CD4 count less than 300 cell/mm3 had GLS value significantly lower than -18% (P value of 0.05).&#x0D; Conclusion: HIV infected population without established cardiovascular disease have subclinical left ventricular dysfunction revealed by GLS imaging technique.

Increased Risk of Anemia, Neutropenia, and Thrombocytopenia in People With Human Immunodeficiency Virus and Well-Controlled Viral Replication

Prior to the introduction of combination antiretroviral therapy (cART), cytopenias were common in people with human immunodeficiency virus (PWH), but it is unknown if well-controlled HIV infection is a risk factor for cytopenia. In this study we aimed to determine if HIV infection is an independent risk factor for anemia, neutropenia, lymphocytopenia, and thrombocytopenia. PWH with undetectable viral replication and absence of chronic hepatitis infection (n = 796) were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) study and matched uninfected controls from the Copenhagen General Population Study (n = 2388). Hematology was analyzed in venous blood samples. Logistic regression analyses adjusted for age, sex, ethnicity, smoking status, alcohol, and high-sensitivity C-reactive protein were performed to determine possible associations between HIV and cytopenias. PWH had a higher prevalence of anemia (6.9% vs 3.4%, P < .001), neutropenia (1.3% vs 0.2%, P < .001), and thrombocytopenia (5.5% vs 2.7%, P < .001) compared with uninfected controls. HIV was independently associated with anemia-adjusted odds ratio (aOR) of 2.0 (95% confidence interval [CI], 1.4-3.0); neutropenia aOR, 6.3 (95% CI, 2.0-19.6); and thrombocytopenia aOR, 2.7 (95% CI, 1.8-4.2). No association was found between HIV and lymphocytopenia. Cytopenia is rare in people with well-controlled HIV, but HIV remains a risk factor for anemia, neutropenia, and thrombocytopenia and requires ongoing attention and monitoring.

Abstract 5044: Prostate adenocarcinoma incidence and risk factors in Veterans with well controlled HIV infection

Abstract (a) Although prostate cancer is projected to be one of the most frequently diagnosed cancers in HIV-infected men overall, little is known about its risk in the sub-group with well-controlled HIV-infection. (b) We performed a retrospective cohort study to determine age-adjusted incidence of prostate adenocarcinoma in HIV-positive male veterans utilizing Veterans Administration (VA) healthcare between 10/01/1999 and 12/31/2016. HIV infection and prostate adenocarcinoma diagnosis as well as related clinical, sociodemographic, and lifestyle risk factors were obtained using extant VA administrative healthcare databases, the VA cancer registry, and augmented prostate cancer diagnosis with direct electronic medical record (EMR) review. We defined well controlled HIV as &amp;gt;60% of time with an undetectable HIV viral load and limited our analyses to those with a minimum of 90 days between HIV and prostate diagnosis, death, their last recorded health care encounter, or study end. We employed time-varying Cox proportional hazard regression models and used backward elimination to identify risk factors associated with incident prostate adenocarcinoma; effects are reported as Hazard ratios (HR) and 95% confidence intervals (CI). (c) During an average 10.26 years of follow-up, we identified 587 incident prostate adenocarcinomas among our cohort of 19,079 HIV positive men with well-controlled infection (age-adjusted incidence rate [IR] = 83.31 per 100,000-person years, 95% CI: 76.83-90.33); with a significant increasing trend over time. We identified several factors associated with significant increased risk of incident prostate adenocarcinoma, after adjusting for HIV medication use, in our well-controlled HIV-positive cohort including substance abuse (HR=1.68, 95% CI: 1.27-2.24, p=0.0003), age at HIV diagnosis (HR=1.73, 95% CI: 1.25-2.39, p=0.0010), and black race (HR=2.07, 95% CI: 1.58-2.72, p&amp;lt;.0001). History of alcohol abuse (HR=0.54, 95% CI: 0.39-0.75, p=0.0002), longer time with well-controlled infection (HR=0.63, 95% CI: 0.59-0.67, p&amp;lt;.0001), and receiving integrase inhibitors (HR=0.64, 95% CI: 0.45-0.92, p=0.041) were associated with reduced risk. Several risk factors included in the multivariable model, such as PSA testing, testosterone levels, and maximum BMI, were not found to be significantly associated with or protective for prostate cancer. (d) Further research is needed to confirm our findings and to better identify sub-groups of well-controlled HIV-positive men at greatest increased prostate cancer risk. Citation Format: Kathryn E. Royse, Jose M. Garcia, Donna L. White, Jennifer R. Kramer, Yongquan Dong, Suchismita Raychaudhury, Peter A. Richardson, Christine Hartman, Elizabeth Y. Chiao. Prostate adenocarcinoma incidence and risk factors in Veterans with well controlled HIV infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5044.

PSORIASIFORM MUCOSITIS BY ANY OTHER NAME… A CASE REPORT AND LITERATURE REVIEW OF ORAL PSORIASIS

A 60–year-old male presented for evaluation of “gum” lesions noted by an oral surgeon. The patient had been treated with chlorhexidine rinse, but the lesions had persisted. The medical history was significant for diabetes mellitus type 2, well-controlled HIV infection, and cutaneous psoriasis. On examination, multiple red macules were noted on the palate. Exfoliative cytology was performed and the patient treated empirically for erythematous candidiasis. On return for re-evaluation, the oral lesions had become widespread. The patient reported that he had discontinued apremilast for insurance reasons, and his cutaneous lesions had also worsened. Exfoliative cytology was negative for Candida organisms. A biopsy of the palatal lesions was recommended and a tentative diagnosis of oral psoriasis rendered. Microscopic examination revealed hyperparakeratosis and psoriasiform mucositis. Since the oral lesions were asymptomatic, the patient was reassured and advised to return for evaluation one month after resumption of psoriasis medication. Clinical assessment is ongoing.

Incidence and significance of an elevated red blood cell distribution width among hospitalised HIV-infected adult patients.

We audited the records of unselected hospitalised HIV-positive adults admitted to a University-affiliated inner London hospital to identify the frequency of elevated red blood cell distribution width (RDW), and potential associations with specific diagnoses, and with outcome. Of 259 patients audited, 188 (73%) were men. Patients’ median age was 47 years (interquartile range = 41–54). An elevated RDW was seen in 50 patients (19%); 200 (77%) had an elevated C-reactive protein (CRP), and 77 (30%) had a low haemoglobin. Only five patients had an elevated RDW without an elevated CRP and/or low haemoglobin. An elevated RDW was associated with a wide range of infectious, inflammatory, and malignant conditions similar to observed associations reported in the general non-HIV infected adult population. Additionally an elevated RDW occurred both in patients with well-controlled HIV infection and in receipt of antiretroviral therapy, as well as in those with newly diagnosed and poorly-controlled infection. Five (10%) of 50 patients with an elevated RDW needed intensive care unit (ICU) admission and two (4%) died. Two (0.95%) of 209 patients with a normal RDW needed ICU admission and four (1.9%) died. The findings of this audit are limited by the relatively small number of patients and the single site nature of the audit.

Kaposi sarcoma.

Kaposi sarcoma (KS) gained public attention as an AIDS-defining malignancy; itsappearance on the skin was a highly stigmatizing sign of HIV infection during the height of the AIDS epidemic. The widespread introduction of effective antiretrovirals to control HIV by restoring immunocompetence reduced the prevalence of AIDS-related KS, although KS does occur in individuals with well-controlled HIV infection. KS also presents in individuals without HIV infection in older men (classic KS), in sub-Saharan Africa (endemic KS) and in transplant recipients (iatrogenic KS). The aetiologic agent of KS is KS herpesvirus (KSHV; also known as human herpesvirus-8), and viral proteins can induce KS-associated cellular changes that enable the virus to evade the host immune system and allow the infected cell to survive and proliferate despite viral infection. Currently, most cases of KS occur in sub-Saharan Africa, where KSHV infection is prevalent owing to transmission by saliva in childhood compounded by the ongoing AIDS epidemic. Treatment for early AIDS-related KS in previously untreated patients should start with the control of HIV with antiretrovirals, which frequently results in KS regression. In advanced-stage KS, chemotherapy with pegylated liposomal doxorubicin or paclitaxel is the most common treatment, although it is seldom curative. In sub-Saharan Africa, KS continues to have a poor prognosis. Newer treatments for KS based on the mechanisms of its pathogenesis are being explored.

Systematic De-escalation of Successful Triple Antiretroviral Therapy to Dual Therapy with Dolutegravir plus Emtricitabine or Lamivudine in Swiss HIV-positive Persons

BackgroundStudies increasingly suggest that the efficacy of certain dual antiretroviral therapy (ART) combinations is equal to triple ART. Increasing concerns among HIV-positive patients and physicians in Switzerland include ART cost and long-term ART safety and toxicity, i.e. taking only as many ART agents as necessary. The aims of this retrospective analysis are to report on the de-escalation of our entire clinic population of eligible patients with well-controlled HIV-infection to dolutegravir-containing dual ART. MethodsStarting in March 2015, we systematically considered the de-escalation of eligible patients to either dolutegravir/emtricitabine or dolutegravir/lamivudine, by discontinuing tenofovir disoproxil fumarate or abacavir. We report on the virological efficacy, tolerability and patient satisfaction ≥ 48 weeks after de-escalation. FindingsOf 106 HIV-positive patients followed in our clinic, 70 patients were de-escalated. Three returned to triple ART (insomnia after dolutegravir start, n = 2; new wish for single tablet regimen, n = 1). All de-escalated patients and all who continued triple ART had suppressed HIV viremia at last follow-up and were satisfied with their ART regimen, except for one patient who had virological failure after ART discontinuation in the setting of major depression. The most common reasons to not de-escalate included hepatitis B co-infection (n = 6), physician's concern about ART adherence (n = 6), patient reluctance to switch from a single tablet to a 2-tablet regimen (n = 7), patient satisfied with current ART (n = 5) and others (n = 12). InterpretationART de-escalation to dolutegravir/FTC or dolutegravir/3TC is possible in the majority of patients virologically suppressed on triple ART, and may effectively address patient and physician concerns about long-term safety and cost of ART.

Early Introduction of cART Reverses Brain Aging Pattern in Well-Controlled HIV Infection: A Comparative MR Spectroscopy Study.

Introduction: The aim of this study was to compare age-related changes in chronically infected, asymptomatic HIV-positive patients under combination antiretroviral therapy (cART), with age-, gender-, and educational-level-matched healthy subjects, using multi-voxel magnetic-resonance spectroscopy (MRS).Methods: There were 66 chronically infected HIV-positive subjects and 65 age-, gender-, and educational-level-matched control subjects, divided into four groups according to the age: group 1 (20–29 years old), group 2 (30–39), group 3 (40–49) and group 4 (50–59). MRS was performed and ratios of N-acetyl-aspartate (NAA)/creatine (Cr) were analyzed in ten locations of the supracallosal gray matter. For the comparison of NAA/Cr ratios in healthy and HIV-positive subjects, ANCOVA with age and education as covariates was performed. Correlations of NAA/Cr ratios with duration of cART were performed using Pearson’s correlation test. Statistical significance was set at p < 0.05.Results: The NAA/Cr ratios were decreased in the 20–29-year-old HIV-positive subjects in 8/10 locations (p < 0.005) compared to the healthy controls, while in the 50–59-year-old groups they were significiantly lower only in one location (p = 0.004). There were significant positive correlations of NAA/Cr levels with the duration of cART in the oldest group of HIV-positive subjects, while in the youngest group there were no significant correlations.Conclusion: The aging pattern in chronic HIV infection under cART is accentuated rather than accelerated. There is an initial HIV-related neuronal damage with a significant decline in NAA/Cr ratios; after the initiation of cART, however, NAA/Cr ratios increase continuously to become similar to healthy aging individuals, probably due to beneficial effect of long-standing cART.Summary: Brain aging in chronic HIV infection under cART is accentuated, with an initial HIV-related neuronal damage followed by a subtle NAA/Cr increase after the initiation of cART. Under cART, in advanced age, NAA/Cr ratios become similar to healthy aging individuals.

Personalized Risk Index for Neurocognitive Decline Among People With Well-Controlled HIV Infection.

Little is known about the predictors of neurocognitive decline in HIV+ individuals with good virological control. Identification of modifiable risk factors would allow targeted interventions to reduce the risk of decline in higher risk individuals. The objective of this study was to develop a risk index to predict neurocognitive decline over 3 years in aviremic HIV+ individuals. As part of the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study, HIV+ adults completed clinical evaluation and neuropsychological tests every 6 months. Group-based trajectory analysis was used to detect patterns of neurocognitive change; individuals who deteriorated ≥ 0.5 SD on at least one neuropsychological test were considered decliners. Multiple logistic regression was used to identify baseline sociodemographic, clinical, biological, and lifestyle factors associated with decline in the subgroup that was consistently aviremic during the first 3 years. A risk index was developed using the beta-coefficients from the final regression model. Neurocognitive decline occurred in 23 of 191 (12%) participants followed longitudinally. The baseline factors that predicted decline were glomerular filtration rate ≤50 mL/min, known duration of HIV infection ≥15 years, education ≤12 years, and cerebrospinal fluid protein >45 mg/dL. Using this analytic approach, neurocognitive decline was uncommon in this sample of aviremic HIV+ individuals. The 3-year risk of decline ranged from 2% in those with no risk factors to 95% in those with all 4. The strongest predictor was glomerular filtration rate, also a predictor of cardiovascular disease. This raises the possibility that controlling vascular risk factors could reduce the risk of neurocognitive decline.

Four-year persistence of type-specific immunity after quadrivalent human papillomavirus vaccination in HIV-infected children: Effect of a fourth dose of vaccine

ObjectiveAlthough HIV-infected children are recommended to receive quadrivalent human papillomavirus vaccine (QHPV) there is limited information on their response to QHPV. This study in HIV-infected children, evaluated the magnitude and duration of immune responses to QHPV. This report describes type-specific serum antibody responses over a 4-to-5year period after either 3 or 4 doses of QHPV. Design/methodsHIV-infected children, ages 7-to-11years, received 3 doses of QHPV (n=96) or placebo (n=30). At 72weeks QHPV recipients received a fourth dose (n=84), while placebo recipients began the 3-dose QHPV schedule (n=27). HPV serotype-specific antibody was determined, by competitive Luminex immunoassay (cLIA) and IgG Luminex immunoassay, at 2, 3.5, and 4-to-5years after the last dose of QHPV in each treatment arm. ResultsAt 4-to-5years after the last dose of QHPV, antibody titers were significantly higher in 4-dose than in 3-dose group. However, the proportion of vaccinees with a seroresponse in the cLIA assay was not different between the two groups (86–93% for HPV types 6, 11, and 16, and 64% for HPV type 18). These results were very similar to the seroresponse rate in these HIV-infected children at 1month after completing vaccination. ConclusionsChildren with well-controlled HIV infection who receive 3 doses of the QHPV vaccine maintain seropositivity and antibody levels that are generally similar to children of the same age who are not HIV-infected. Antibody titer correlated strongly with low log HIV RNA, low CD8%, and high CD4%. Additionally, a fourth dose of vaccine in HIV-infected children produces a marked rise in antibody characteristic of an anamnestic response and persistence of high antibody levels.Study identification: IMPAACT P1085 (V501-021). CLINICALTRIALS.GOV identifier: NCT01206556.

Contemporary Recommendations for Primary Care Management of Patients with HIV Infection

The morbidity and mortality associated with HIV infection has decreased significantly in the current era of antiretroviral therapy, with HIV-infected individuals now anticipating a normal life expectancy in developed countries. HIV has transformed from a disease of certain death into a chronic condition that can be managed medically. Reflecting this change, the Infectious Disease Society of America (IDSA) recently released an update on the management of HIV with a new emphasis on primary care and enhanced screening for comorbid conditions. For individuals with well-controlled HIV infection, the frequency of viral load and CD4 cell count monitoringcan is reduced from every 3-4 months to every 6-12 months. Increased attention is devoted to immunizations with new recommendations for HPV vaccination in males and an updated pneumococcal vaccination schedule. There is also an enhanced section on sexually transmitted diseases including annual screening for trichomoniasisin women, yearly screening for gonorrhea and chlamydia in at risk individuals, and anal cytologic screening in certain risk groups. This article reviews the 2013IDSA guidelines, highlights significant changes from prior IDSA guidelines, and contrasts these recommendations with other United States screening guidelines.

Hepatitis C virus (HCV) RNA profiles among chronic HIV/HCV-coinfected individuals in ESPRIT; spontaneous HCV RNA clearance observed in nine individuals.

Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among those with the CC interleukin (IL)-28B genotype. This study describes HCV RNA profiles and factors associated with changes over time in HCV RNA levels in the ESPRIT study. HIV/HCV-coinfected individuals positive for HCV RNA were included in the study. Follow-up was counted from the first HCV RNA positive test and censored at the initiation of interferon-based treatment. HCV RNA and IL-28B measurements were performed in the same reference laboratory. Random effects mixed models were used to analyse changes over time in HCV RNA. A total of 312 ESPRIT patients were included in the study (151 in the arm receiving subcutaneous recombinant IL-2 and 161 in the control arm). Most of the patients were white (89%) and male (76%), and they had a median of 5 HCV RNA measurements per person [interquartile range (IQR) 3-6; range 1-9]. Median follow-up was 5 years (IQR: 2-6 years). At baseline, 96% of patients were taking cART and 93% had undetectable HIV RNA. Mean HCV RNA levels decreased by 13% per year over the study period [95% confidence interval (CI) 8-18%; P < 0.0001]. Baseline HCV RNA levels and the change over time in HCV RNA did not differ by randomization arm (P = 0.16 and P = 0.56, respectively). Nine individuals spontaneously cleared HCV RNA during follow-up [IL-28B genotypes: CC, five patients (56%); CT, four patients (44%)]. HCV RNA levels decreased over time in this population with well-controlled HIV infection. Spontaneous clearance of HCV RNA was documented in five individuals with IL-28B genotype CC and four with the CT genotype.