Nadir CD4 Cell Count Research Articles

Therapeutic drug monitoring of boosted PIs in HIV-positive patients: undetectable plasma concentrations and risk of virological failure

Therapeutic drug monitoring (TDM) of antiretroviral drugs is performed in selected HIV-positive patients. The aim of this study was to estimate the prevalence of undetectable plasma concentrations of ritonavir and boosted PIs and to evaluate the association between those and the 48 week risk of virological failure. A TDM registry study and a retrospective follow-up study were conducted. Plasma concentrations were measured through validated methods. According to PI and ritonavir concentrations, patients were stratified as adherent, partially non-adherent or non-adherent. Virological outcome was evaluated 48 weeks afterwards. The TDM registry study included 2468 samples collected from 723 patients (68.1% male, median age 43.5 years). Eighty-seven samples (3.5%, 74 patients) and 68 samples (2.8%, 52 patients) were in the partially non-adherent and non-adherent groups, respectively; more patients on atazanavir/ritonavir (7.9%) versus darunavir/ritonavir (2% twice daily and 1.9% once daily) and lopinavir/ritonavir (1.5%; P < 0.001) were observed in the partially non-adherent group. Two hundred and ninety patients were included in the follow-up study (64.1% male, median age 40 years). Patients in the adherent group had a higher chance of viral control [81.9% (167/204)] versus the partially non-adherent group and the non-adherent group [71.7% (33/46) and 53.1% (17/32), respectively; P = 0.001]. Based on multivariate analysis, baseline HIV RNA >50 copies/mL ( P < 0.001), genotypic susceptibility score ≤2 ( P = 0.001), lower nadir CD4 cell count ( P = 0.003) and not being in the adherent group ( P = 0.029) were independent predictors of HIV RNA >50 copies/mL at 48 weeks. The measurement of PI and ritonavir plasma levels can uncover incomplete compliance with treatment; TDM may represent a useful tool for identifying patients in need of adherence-promoting interventions.

Predictors and incidence of sexually transmitted Hepatitis C virus infection in HIV positive men who have sex with men

BackgroundSexual transmission of Hepatitis C virus (HCV) in men who have sex with men (MSM) and its interaction with HIV status, sexually transmitted infections and sexual behaviour is poorly understood. We assessed the incidence and predictors of HCV infection in HIV positive MSM.MethodsThe electronic medical record and laboratory results from HIV positive MSM in care at a large urban public specialist HIV clinic embedded in a sexual health centre in Melbourne Australia were collected. Patients with two or more HCV antibody tests between January 2008 and March 2016 and with no record of injecting drug use were included. The HCV exposure intervals were the periods between a negative HCV test and the next HCV test. We compared HCV exposure intervals temporally associated with and without newly acquired syphilis or anorectal chlamydia. HCV exposure intervals were also categorised as being before or after HIV virological suppression and by most recent and nadir CD4 cell count.ResultsThirty seven new HCV infections were diagnosed in 822 HIV positive MSM with no history of injecting drug use over 3114 person years (PY) of follow-up. Mean age was 43.1 years (±12.5) and mean CD4 cell count nadir was 362 cells/uL (±186). The incidence of HCV infection in the study population was 1.19/100PY (0.99–1.38). The incidence in exposure periods temporally close to new syphilis infection was 4.72/100PY (3.35–6.08) and to new anorectal chlamydia infection was 1.37/100PY (0.81–1.93). The incidence in men without supressed viral load was 3.19/100PY (1.89–4.49). In the multivariate Cox regression analysis only younger age (aHR 0.67 (0.48–0.92)), exposure periods temporally associated to new syphilis infection (aHR 4.96 (2.46–9.99)) and higher CD4 cell count nadir (aHR 1.26 per 100 cells/uL (1.01–1.58)) were associated with increased risk of HCV infection. During the study period the incidence of syphilis increased dramatically but the incidence of HCV infection remained the same.ConclusionsIncidence of HCV infection is associated with syphilis but not anorectal chlamydia which suggests a biological rather than behavioural risk modification. Rising syphilis incidence may offset declines in HCV transmission through HCV treatment as prevention.

Outcomes following detection of low level plasma HIV RNA in HIV-infected patients previously virologically suppressed on antiretroviral therapy: a retrospective observational study

Progressively sensitive assays for plasma HIV RNA have led to increased detection of plasma HIV RNA between 20 and 200 copies/ml, known as low level viremia (LLV) when recurrent or persistent, in HIV-infected patients on antiretroviral therapy (ART). The aim of this study was to determine outcomes following initial detection of LLV in an Australian cohort. A retrospective study using the HIV Service Database (Alfred Hospital) included all patients on ART who recorded plasma HIV RNA 20-200 copies/mL following prior virological suppression (viral load (VL) HIV RNA <20 copies/mL) over 2 years (2010 to 2012), with follow-up to June 2013. Factors associated with subsequent virological outcome were assessed via univariate and multivariate analysis. Of 919 patients managed by The Alfred HIV service, 207 (22.5%) met inclusion criteria. Mean age was 48.8 years, 91.3% were male. During follow-up, 54% patients recorded no further HIV RNA 20-200 copies/mL (viral blip); 39% had recurrent or persistent VL 20-200 copies/mL (LLV); and 7% progressed to virological failure with VL >200 copies/mL. Factors associated with LLV included co-morbid type 2 diabetes, shorter prior virological suppression and lower nadir CD4 cell count. Clinician management of VL 20-200 copies/mL was generally conservative, with infrequent requests for genotypic analysis (3.3% cases) or change in ART (<1% cases). LLV following virological suppression is common, and occurred as an isolated viral blip in half the patients. Those patients with persistent or recurrent LLV had higher rates of type 2 diabetes, shorter prior virological suppression and lower nadir CD4 cell count.

Prevalence and predictors of low muscle mass in HIV/viral hepatitis coinfection.

Low muscle mass is associated with reduced survival in HIV, possibly mediated by systemic inflammation. Viral hepatitis coinfection can induce additional inflammation and hepatic dysfunction that may exacerbate low muscle mass. We determined the prevalence of and risk factors for low muscle mass in HIV/viral hepatitis coinfection. A cross-sectional study of participants in the Multicenter AIDS Cohort Study and Women's Interagency HIV Study with anthropometry performed after 1 January 2000. Viral hepatitis defined by positive hepatitis B virus surface antigen and/or hepatitis C virus RNA. Low muscle mass defined as less than 10th percentile of age-matched and sex-matched reference values for mid-upper arm circumference. Using multivariable logistic regression, we determined adjusted odds ratios with 95% confidence intervals (CIs) of the association of HIV/viral hepatitis coinfection with low muscle mass and factors associated with low muscle mass in coinfected persons. Analyses adjusted for age, race, BMI, alcohol use, and IDU (also, nadir CD4 cell count and HIV RNA where appropriate). Among 3518 participants (164 HIV/viral hepatitis, 223 viral hepatitis alone, 1070 HIV alone, and 2061 uninfected), HIV/viral hepatitis-coinfected persons had a 3.50-fold (95% CI, 1.51-8.09), 1.93-fold (1.17-3.20), and 2.65-fold (1.62-4.35) higher odds of low muscle mass than viral hepatitis-monoinfected, HIV-monoinfected, and uninfected persons, respectively. Lack of HIV RNA suppression [odds ratio, 2.26 (95% CI, 1.10-4.63)] was the only factor associated with low muscle mass in coinfected persons. HIV/viral hepatitis-coinfected persons have a higher likelihood of low muscle mass than those with viral hepatitis monoinfection, HIV monoinfection, or neither infection. HIV viremia is an important risk factor for low muscle mass among coinfected persons.

Clinical and Emotional Factors Related to Erectile Dysfunction in HIV-Infected Men.

The prevalence and associated factors of erectile dysfunction (ED) in Human Immunodeficiency Virus (HIV)–infected men remain controversial. The authors evaluated ED, clinical, and emotional variables in a group of 501 HIV-infected men in a cross-sectional 4-month observational study. ED was assessed using the International Index of Erectile Function–5 and emotional status using the Hospital Anxiety and Depression (HAD) questionnaire. Median age (interquartile range) was 42 (35, 48) years. Time since HIV diagnosis was 6.3 (2.6, 17.1) years, 92% were taking antiretroviral treatment and 81.8% had an HIV-RNA viral load <50 copies. The prevalence of ED was 58.5%. ED was mild in 30.1%, mild to moderate in 19.5%, moderate in 6.1%, and severe in 2.5%. ED medications were used by 19% of men. In the univariate analysis, the variables associated with all degrees of ED were older age, longer time since HIV diagnosis, higher scores in HAD, not taking efavirenz, taking etravirine, taking ritonavir, HIV/Hepatitis C Virus coinfection, and taking a protease inhibitor-containing regimen. For mild to moderate, moderate, and severe ED, the same variables were significant, as were lower nadir CD4 cell count, lower social support, taking atazanavir, concomitant conditions, and concomitant treatments. The variables that remained significant in the multivariate analyses, considering all degrees of ED or excluding mild ED were the following: older age and higher scores in HAD total. In summary, ED affected more than half of this cohort of well controlled HIV-infected men. Age and emotional status seemed to play a fundamental role in its presence.

Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications.

HIV-1 DNA persists in infected cells despite combined antiretroviral therapy (cART), forming viral reservoirs. Recent trials of strategies targeting latent HIV reservoirs have rekindled hopes of curing HIV infection, and reliable markers are thus needed to evaluate viral reservoirs. Total HIV DNA quantification is simple, standardized, sensitive, and reproducible. Total HIV DNA load influences the course of the infection and is therefore clinically relevant. In particular, it is predictive of progression to AIDS and death, independently of HIV RNA load and the CD4 cell count. Baseline total HIV DNA load is predictive of the response to cART. It declines during cART but remains quantifiable, at a level that reflects both the history of infection (HIV RNA zenith, CD4 cell count nadir) and treatment efficacy (residual viremia, cumulative viremia, immune restoration, immune cell activation). Total HIV DNA load in blood is also predictive of the presence and severity of some HIV-1-associated end-organ disorders. It can be useful to guide individual treatment, notably, therapeutic de-escalation. Although it does not distinguish between replication-competent and -defective latent viruses, the total HIV DNA load in blood, tissues, and cells provides insights into HIV pathogenesis, probably because all viral forms participate in host cell activation and HIV pathogenesis. Total HIV DNA is thus a biomarker of HIV reservoirs, which can be defined as all infected cells and tissues containing all forms of HIV persistence that participate in pathogenesis. This participation may occur through the production of new virions, creating new cycles of infection and disseminating infected cells; maintenance or amplification of reservoirs by homeostatic cell proliferation; and viral transcription and synthesis of viral proteins without new virion production. These proteins can induce immune activation, thus participating in the vicious circle of HIV pathogenesis.

Cervical HPV infection in Romanian women infected with HIV during early childhood.

Human papillomavirus (HPV) is the most common cause of cervical cancer worldwide, and Romania has the highest rate of cervical cancer in Europe. Sixty-five young Romanian women infected with HIV during early childhood and 25 control subjects were evaluated for the presence of cervical HPV infection and for cytologic abnormalities. HPV infection was evaluated longitudinally in 42 HIV-infected individuals. Overall 28/65 (43.1%) of HIV-infected and 8/25 (32.0%) of uninfected subjects were infected with HPV, and 21/65 (32.3%) and 6/25 (24%) had high-risk subtypes, respectively. In HIV-infected women, those maintaining or acquiring a new subtype in follow-up were more likely to have a lower nadir (p = 0.04) and current (p = 0.01) CD4 cell counts. The incidence rate for HPV acquisition events was 0.69 per subject per year, and 0.52 for high-risk subtypes. In the HIV-infected group, 9/13 (69.2%) individuals with abnormal cytology progressed at follow-up. Although HPV prevalence was similar to controls, the rate of Pap smear abnormalities was much higher, possibly due to the decreased ability to mount new immune responses. Given the high rate of incident detection of vaccine preventable strains and cytologic progression in this cohort, HPV vaccination may be beneficial at any age in co-infected women.

Incidence and risk factors of fever in a contemporary cohort of HIV-patients with good access to antiretroviral therapy

Objective: To study incidence and to determine risk factors of fever in a contemporary cohort of HIV-infected patients with access to antiretroviral therapy.Methods: Prospective study in a cohort of HIV-infected patients in Belgium from 2009 to 2013.Results: 759 patients were followed for a total of 2136 patient years. The incidence of fever was low, with an incidence rate of 0.103 (95% CI 0.078; 0.135) febrile episodes per patient per year for temperature 38.3 °C or higher measured by a health care provider. Gender, age, ethnicity, and calendar year of measurement were no significant risk factors for fever in univariable analysis, but recent HIV diagnosis, prior AIDS, nadir CD4 cell count, last CD4 cell count, and viral load were, as were use of antiretroviral therapy, recent start of antiretroviral therapy and recent switch of antiretroviral therapy. Recent stop of antiretroviral therapy was no significant risk factor. In multivariable analysis prior AIDS, last CD4 and viral load remained significant risk factors, but use of antiretroviral therapy not.Conclusion: In this contemporary cohort, incidence of fever was low but CD4 cell count less than 200/mm³ remained associated with the highest incidence of fever.

Six-month survival of critically ill patients with HIV-related disease and tuberculosis: a retrospective study.

BackgroundTuberculosis is one of the leading causes of death from infectious diseases worldwide, mainly after the human immunodeficiency virus (HIV) epidemics. Patient with HIV-related illness are more likely to present with severe TB due to immunosuppression. Very few studies have explored HIV/TB co-infection in critically ill patients. The goal of this study was to analyze factors associated with long-term mortality in critically ill patient with HIV-related disease coinfected with TB.MethodsWe conducted a retrospective study in an infectious disease reference center in Brazil that included all patient with HIV-related illness admitted to the ICU with laboratory-confirmed tuberculosis from March 2007 until June 2012. Clinical and laboratory variables were analyzed based on six-month survival.ResultsForty-four patients with HIV-related illness with a confirmed diagnosis of tuberculosis were analyzed. The six-month mortality was 52 % (23 patients). The main causes of admission were respiratory failure (41 %), severe sepsis/septic shock (32 %) and coma/torpor (14 %). The median time between HIV diagnosis and ICU admission was 5 (1–60) months, and 41 % of patients received their HIV infection diagnosis ≤ 30 days before admission. The median CD4 count was 72 (IQR: 23–136) cells/mm3. The clinical presentation was pulmonary tuberculosis in 22 patients (50 %) and disseminated TB in 20 patients (45.5 %). No aspect of TB diagnosis or treatment was different between survivors and nonsurvivors. Neurological dysfunction was more prevalent among nonsurvivors (43 % vs. 14 %, p = 0.04). The nadir CD4 cell count lower than 50 cells/mm3 was independently associated with Six-month mortality (hazard ratio 4.58 [1.64–12.74], p < 0.01), while HIV diagnosis less than three months after positive serology was protective (hazard ratio 0.27, CI 95 % [0.10–0.72], p = 0.01).ConclusionThe Six-month mortality of HIV critically ill patients with TB coinfection is high and strongly associated with the nadir CD4 cell count less than 50 cels/mm3.

Factors associated with virological response to a switch regimen containing maraviroc for antiretroviral-experienced HIV-1-infected patients.

There are few data on clinical and virological factors associated with maraviroc virological response (VR) in clinical practice. This study aimed to identify factors associated with VR in 94 treatment-experienced, but CCR5 inhibitor-naive, HIV-1 patients switched to maraviroc-containing regimens. Patients with HIV-1 RNA viral load (VL) <50 copies/mL switching to an antiretroviral treatment containing maraviroc were followed. VR was defined at month 3 as VL <50 copies/mL. The impact of age, baseline tropism, zenith VL, nadir CD4 cell count and CD4 cell count, HIV subtype (B versus non-B), genotypic susceptibility score of treatment, once- or twice-daily treatment and presence of raltegravir in optimized background therapy on VR was investigated. Baseline characteristics were: median age 49 years (range 25-73 years), median CD4 cell count 481 cells/mm(3) (range 57-1830 cells/mm(3)) and median nadir CD4 cell count 99 cells/mm(3) (range 3-585). Maraviroc was administered twice daily in 88 of 94 patients and once daily in 6 of 94 patients (300 mg/day for 4 of 6 and 150 mg/day for 2 of 6). At month 3, 89.4% of patients were responders. A better VR to a switch regimen containing maraviroc was associated with the B subtype (P = 0.0216) and a lower zenith VL (median of 5.24 and 5.70 log10 copies/mL for patients in success or in failure, respectively) in univariate analysis. Only B subtype was associated with a better VR in multivariate analysis. This study evidenced the efficacy of a switch regimen containing maraviroc in clinical practice. VR was better for patients with a lower zenith VL and B subtype.

Decay of ccc-DNA marks persistence of intrahepatic viral DNA synthesis under tenofovir in HIV-HBV co-infected patients

In the presence of highly-potent antivirals, persistence of hepatitis B virus (HBV) is most well-characterized by covalently-closed circular DNA (cccDNA) and total intrahepatic DNA (IH-DNA). We sought to determine how antiviral therapy could affect their levels during human immunodeficiency virus (HIV)-HBV co-infection. Sixty co-infected patients from a well-defined cohort with ⩾1 liver biopsy were studied. HBV cccDNA and total IH-DNA were extracted from biopsies and quantified by real-time PCR. Factors associated with intrahepatic viral load were determined using mixed-effect linear regression and half-life viral kinetics during reconstructed follow-up using non-linear exponential decay models. At biopsy, 35 (58.3%) patients were hepatitis B "e" antigen (HBeAg)-positive and 33 (55.0%) had detectable plasma HBV-DNA (median=4.58log10IU/ml, IQR=2.95-7.43). Overall, median cccDNA was -0.95log10copies/cell (IQR=-1.70, -0.17) and total IH-DNA was 0.27log10copies/cell (IQR=-0.39, 2.00). In multivariable analysis, significantly lower levels of cccDNA and total IH-DNA were observed in patients with HBeAg-negative serology, nadir CD4(+) cell counts >250/mm(3), and longer cumulative TDF-duration, but not lamivudine- or adefovir-duration. In post-hoc analysis using reconstructed TDF-duration (median 29.6months, IQR=15.0-36.1, n=31), average half-life of cccDNA was estimated at 9.2months (HBeAg-positive=8.6, HBeAg-negative=26.2) and total IH DNA at 5.8months (HBeAg-positive=1.3, HBeAg-negative=13.6). Intrahepatic viral loads remained detectable for all patients, even with prolonged TDF-exposure. In co-infection, TDF-use is associated with lower levels of HBV replication intermediates and cccDNA. Slow decay of intrahepatic viral loads underscores that TDF is unable to completely block intracellular viral DNA synthesis, which possibly accounts for continuous replenishment of the cccDNA pool. Chronic hepatitis B virus (HBV) is a persistent infection, while the only real way of knowing the extent of this persistence is through measuring levels of virus in the liver. In this study, we examine levels of HBV in the liver among patients with both HBV and human immunodeficiency virus, or HIV, infection. It would appear that the currently available medication, namely "tenofovir", works well to decrease virus levels in the liver, but it remains at low levels despite long periods of treatment.

Compensatory activation in fronto-parietal cortices among HIV-infected persons during a monetary decision-making task.

HIV infection can cause direct and indirect damage to the brain and is consistently associated with neurocognitive disorders, including impairments in decision-making capacities. The tendency to devalue rewards that are delayed (temporal discounting) is relevant to a range of health risk behaviors. Making choices about delayed rewards engages the executive control network of the brain, which has been found to be affected by HIV. In this case-control study of 18 HIV-positive and 17 HIV-negative adults, we examined the effects of HIV on brain activation during a temporal discounting task. Functional MRI (fMRI) data were collected while participants made choices between smaller, sooner rewards and larger, delayed rewards. Choices were individualized based on participants' unique discount functions, so each participant experienced hard (similarly valued), easy (disparately valued), and control choices. fMRI data were analyzed using a mixed-effects model to identify group-related differences associated with choice difficulty. While there was no difference between groups in behavioral performance, the HIV-positive group demonstrated significantly larger increases in activation within left parietal regions and bilateral prefrontal regions during easy trials and within the right prefrontal cortex and anterior cingulate during hard trials. Increasing activation within the prefrontal regions was associated with lower nadir CD4 cell count and risk-taking propensity. These results support the hypothesis that HIV infection can alter brain functioning in regions that support decision making, providing further evidence for HIV-associated compensatory activation within fronto-parietal cortices. A history of immunosuppression may contribute to these brain changes. Hum Brain Mapp 37:2455-2467, 2016. © 2016 Wiley Periodicals, Inc.

Prevalence of osteo-renal impairment in the Romanian HIV cohort.

BackgroundThe Romanian HIV cohort has certain particularities that render it unique in Europe. We have performed a study to evaluate the prevalence of bone and kidney impairment in this particular group of HIV-infected patients.MethodsWe performed dual-energy X-ray absorptiometry (DXA) evaluation of the lumbar vertebrae and the femur, as well as laboratory tests including standard serum panels, bone-related markers and urinalysis in patients from the Romanian HIV cohort.ResultsThe study included 72 patients, of which 46 (58.3 %) were males. The median (IQR) age was 38 (18) years and the median (IQR) time from HIV infection diagnosis was 9 (13) years. Most patients (55.6 %) were non-smokers, but a relatively high proportion (37.5 %) was currently smoking. Only a small percentage of patients (20.8 %) did not present any comorbidities, while 40.3 % had one comorbidity, the most frequent being dyslipidemia (present in 25 patients, 38.5 %). Only 6 patients had a medical history suggestive for renal disease and 3 for bone-related abnormalities.The median (IQR) glomerular filtration rate was 97.5 (33.0) mL/min/1.73sqm. We diagnosed 21 patients (29.6 %) with stage 2 chronic kidney disease and one patient (1.4 %) with stage 3 chronic kidney disease. Proteinuria was present in 9 (12.7 %) patients. The estimated glomerular filtration rate was significantly lower in patients with cardiac comorbidities (p = 0.013).Vitamin D was significantly lower in smokers compared with non-smokers, with a mean value of 15 vs. 21 ng/mL and a moderate effect size (Cohen’s d = −0.5) (p = 0.046). Lumbar osteopenia and osteoporosis were diagnosed in 33.3 and 13.7 % of patients, while femoral osteopenia and osteoporosis were diagnosed in 37.3 and 7.8 %, respectively. Lower nadir CD4 cell counts were found in patients with bone-related comorbidities (p = 0.000).ConclusionsWe identified a relatively high prevalence of chronic kidney disease in the Romanian HIV cohort, and a fairly low prevalence of osteopenia and osteoporosis, compared with other European countries. In this category of patients smoking should be avoided altogether, as it may be an indirect risk factor for kidney disease (associating cardiac comorbidities) and it may impair bone metabolism by altering serum levels of hydroxy-vitamin D.

Feasibility and efficacy of early lung cancer diagnosis with chest computed tomography in HIV-infected smokers.

Lung cancer screening with chest computed tomography (CT) is beneficial in smokers aged 55 to 74 years. We studied the risks, benefits and feasibility of early lung cancer diagnosis with CT in HIV-infected smokers. French, multicentre, single round chest CT study in France, realized between February 2011 and June 2012. Patients were HIV-infected smokers at least 40 years, at least 20 pack-years, with a CD4 T-lymphocyte nadir count below 350 cells/μl. Single chest CT with a proposed standardized workup algorithm of positive images. The outcome was the number of histologically proven lung cancers diagnosed by CT with a 2-year follow-up. Median age of the 442 included patients was 49.8 years, 81.6% were under 55 years, 84% were men, median smoking was 30 pack-years, median nadir and last CD4 cell counts were 168 and 574 cells/μl, respectively, and 90% of patients had a plasma HIV RNA below 50 copies/ml. A positive image at baseline was reported in 94 (21%) patients, and 15 (3.4%) patients had 18 invasive procedures with no serious adverse events. Lung cancer was diagnosed in 10 patients (six at early stages), of which nine (2.0%, 95% confidence interval: 0.9-3.8) were CT detected, and eight in patients below 55 years. Early lung cancer diagnosis with CT in HIV-infected smokers was feasible, safe, and yielded a significant number of cancers. Lung cancer screening of HIV-infected smokers with an important history of immunodeficiency revealed a substantial number of cancers at younger ages than the targeted range in the general population.

9. Epidemiological and Immunologic Profile in an Outpatient HIV Clinic in Southeastern Ontario

Kingston represents a unique enclave within Southeastern Ontario owing to the preponderance of correctional facilities within its environs, as well as its geographic location at the crossroads between three of Canada’s largest cities – Toronto, Ottawa and Montreal. This gives the Kingston HIV epidemic a distinctive character. This study provides attempts to construct the epidemiological profile of HIV‐infected patients in Kingston by two prognostic variables –CD4 cell count and viral load– to elucidate any trends in immunologic status and efficacy of treatment for patients followed at the Clinical Immunology Outpatient Clinic (CIOC) in Kingston, Ontario. We conducted a retrospective analysis of HIV‐infected patients managed at the CIOC. Patients were stratified according to gender and year of diagnosis. Median CD4 cell count and viral load at first and most recent visit were compared for both groups. Bivariate analysis of age, gender, HCV co‐infection, nadir CD4 cell count and proportion of patients achieving viral suppression was also undertaken. 528 patients were included in the analysis: 158 active, 106 incarcerated, 94 transferred, 93 known deceased and 77 lost to follow‐up. There were 453 males and 75 females. Male patients had a greater age at diagnosis and a lower proportion of HCV coinfection. Female patients had a greater median CD4 cell count for both the first and most recent visit. There was no significant difference in viral load values between male and female patients. 439 patients had a year of diagnosis on file; 290 were diagnosed before 1997 and 149 were diagnosed in or after 1997. There was no significant change in gender distribution or HCV co‐infection, but patients diagnosed after 1997 had a greater age at diagnosis, a greater first viral load, a greater most recent CD4 cell count and were less likely to be virologically suppressed at first visit. The demographics of patients presenting at the CIOC have been changing in concert with a broader Canada‐wide shift. The findings of this study indicate differences in immunologic status and other prognostic parameters between males and females and a marked shift in demographic and immunologic parameters following the introduction of Highly Active Antiretroviral Treatment (HAART) in 1997. New treatment stratagems will have to be implemented to reflect the changing face of HIV epidemic in Kingston and Ontario.

Performance of genotypic algorithms for predicting tropism of HIV-1CRF02_AG subtype

BackgroundSeveral genotypic rules for predicting HIV-1 non-B subtypes tropism are commonly used, but there is no consensus about their performances. ObjectivesThree genotypic methods were compared for CRF02_AG HIV-1 tropism determination. Study designV3 env region of 178HIV-1 CRF02_AG from Pitié-Salpêtrière and Saint-Antoine Hospitals was sequenced from plasma HIV-1 RNA. HIV-1 tropism was determined by Geno2Pheno algorithm, false positive rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25 and net charge rule. ResultsA concordance of 91.6% was observed between Geno2pheno 5% and the combined criteria. The results were nearly similar for the comparison between Geno2pheno 5% and the 11/25 rule. More mismatches were observed when Geno2pheno was used with the FPR 10%. A lower nadir CD4 cell count was associated with a discordance of tropism prediction between Geno2pheno 5% and the combined criteria or the 11/25 rule (p=0.02 and p=0.03, respectively). A lower HIV-1 viral load was associated with some discordance for the comparison of Geno2pheno 10% and the combined rule (p=0.02). ConclusionGeno2pheno FPR 5% or 10% predicted more X4-tropic viruses for this set of CRF02_AG sequences than the combined criteria or the 11/25 rule alone. Furthermore, Geno2pheno FPR 5% was more concordant with the 11/25 rule and the combined rule than Geno2pheno 10% to predict HIV-1 tropism. Overall, Geno2pheno 5% could be used to predict CRF02_AG tropism as well as other genotypic rules.

Factors associated with long-term CD4 cell recovery in HIV-infected patients on successful antiretroviral therapy.

The aim of the study was to study the factors associated with immunological recovery in HIV-infected patients with suppressed viral load. Nadir and current CD4 cell counts were recorded in 821 patients, as well as many demographic, epidemiological, lifestyle, clinical, therapeutic, genetic, laboratory, liver fibrosis and viral hepatitis parameters. The median age of the patients was 44.4 years [interquartile range (IQR) 40.3-48.0 years], the median time since HIV diagnosis was 15.3 years (IQR 10.5-18.9 years), the median time of suppressed viral load was 7.0 years (IQR 4.0-10.0 years) and the median time on the current antiretroviral regimen was 2.8 years (IQR 1.4-4.7 years). The median nadir and current CD4 counts were 193.0 (IQR 84.0-301.0) and 522.0 (IQR 361.0-760) cells/μL, respectively, separated by a median period of 10.2 years (IQR 5.9-12.9 years). The median CD4 count gain during follow-up was 317.0 (IQR 173.0-508.0) cells/μL. Many variables were associated with CD4 cell gains in univariate analyses, including age, gender, epidemiology, prior clinical conditions, fibrosis stage, transient elastometry, aspartate aminotransferase (AST), nadir CD4 count and hepatitis B and C virus infections and genotypes, as well as the durations of follow-up since nadir CD4 count, overall antiretroviral treatment, current antiretroviral regimen, protease inhibitor therapy and suppression of viral load. Multivariate analysis revealed that longer duration of HIV suppression (P < 0.0001), more advanced clinical Centers for Disease Control and Prevention (CDC) stages (P < 0.0001), younger age (P = 0.0003), hepatitis C virus genotypes 1 and 4 (P = 0.003), sexual acquisition of HIV (P = 0.004), and lower transient elastometry values (P = 0.03) were independent predictors of CD4 cell gains. Overall, the model accounted for 14.2% of the variability in CD4 count. In addition to the duration of HIV suppression, HIV-related diseases, HIV epidemiology, age, hepatitis C virus genotypes, and liver fibrosis were independently associated with long-term immunological recovery.

Cerebral vasoreactivity is impaired in treated, virally suppressed HIV-infected individuals.

To compare cerebral vasoreactivity, a measure of cerebrovascular endothelial function, between treated, virally suppressed HIV-infected individuals and HIV-uninfected controls and to evaluate the effect of HIV-specific factors on cerebral vasoreactivity. Cross-sectional study of 65 antiretroviral therapy-treated, virally suppressed HIV-infected individuals and 28 HIV-uninfected controls. Participants underwent noninvasive assessment of cerebral vasoreactivity using transcranial Doppler ultrasound and inhaled carbon dioxide (CO2). We used mixed effects multivariable linear regression to determine the association of HIV infection and HIV-specific factors with cerebral vasoreactivity. Mean age was 57.2 years for HIV-infected participants and 53.5 years for HIV-uninfected controls. Most participants (95%) were men. Twenty-six per cent of HIV-infected participants were nonwhite compared to 32% of controls. Among HIV-infected participants, mean CD4 cell count was 596 cells/μl, and mean duration of viral suppression was 7.8 years. Cerebral vasoreactivity in response to hypercapnia (cerebral VRhyper) was lower in HIV-infected individuals compared to uninfected controls (3.23 versus 3.81%, P = 0.010). After adjusting for demographic and vascular risk factors, HIV infection was independently associated with lower cerebral vasoreactivity (-0.86%, 95% CI -1.30 to -0.42%, P < 0.001). We did not find a statistically significant effect of recent or nadir CD4 cell count on cerebral vasoreactivity. There was a trend toward higher cerebral vasoreactivity for each additional year of viral suppression. Treated, virally suppressed HIV infection negatively impacted cerebral vasoreactivity even after adjustment for traditional vascular risk factors. These data highlight the potential contribution of cerebrovascular endothelial dysfunction to the elevated risk of stroke observed in HIV-infected individuals.

High rate of lymphoma among a UK cohort of adolescents with vertically acquired HIV-1 infection transitioning to adult care in the era of antiretroviral therapy.

Among an inner London UK cohort of 147 adolescents transitioning from paediatric into adult care between 2007 and 2015, a new diagnosis of lymphoma was made in five patients; incidence rate = 0.425/100 person-years (95% confidence interval = 0.424-0.426). Previously described risk factors, including low nadir CD4 cell count and ongoing HIV-1 viraemia, appeared to be important. These data suggest that careful surveillance and a low threshold for investigating relevant symptoms continue to be essential for such patients.

Incidence and predictors of hypertension in adults with HIV-initiating antiretroviral therapy in south-western Uganda.

The successful scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has led to increasing life expectancy, and thus increased risk of hypertension. We aimed to describe the incidence and predictors of hypertension in HIV patients receiving ART at a publicly funded clinic in rural Uganda. We abstracted data from medical records of adult patients who initiated ART at an HIV clinic in south-western Uganda during 2010-2012. We defined hypertension as at least two consecutive clinical visits, with a SBP at least 140 mmHg and/or SBP of at least 90 mmHg, or prescription for an antihypertensive medication. We calculated the incidence of hypertension and fit multivariable Cox proportional-hazards models to identify predictors of hypertension. A total of 3389 patients initiated ART without a prior diagnosis of hypertension during the observation period. Over 3990 person-years of follow-up, 445 patients developed hypertension, for a crude incidence of 111.5/1000 (95% confidence interval 101.9-121.7) person-years. Rates were highest among men aged at least 40 years (158.8 per/1000 person-years) and lowest in women aged 30-39 years (80/1000 person-years). Lower CD4 cell count at ART initiation, as well as traditional risk factors including male sex, increasing age, and obesity, were independently associated with hypertension. We observed a high incidence of hypertension in HIV-infected persons on ART in rural Uganda, and increased risk with lower nadir CD4 cell counts. Our findings call for increased attention to screening of and treatment for hypertension, along with continued prioritization of early ART initiation.