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1.
HIV Med ; 21(5): 309-321, 2020 05.
Article in English | MEDLINE | ID: mdl-31927793

ABSTRACT

OBJECTIVES: The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes. METHODS: We identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1 year. We analysed outcomes of viral suppression (< 200 HIV-1 RNA copies/mL) and appearance of new major drug resistance mutations (DRMs) using Cox and Poisson models, with stratification by new drug regimen (excluding 3TC/FTC) and Bayesian implementation, and estimated the effect of 3TC/FTC adjusted for individual and viral characteristics. RESULTS: We included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. We found a negative adjusted association between 3TC/FTC use and viral suppression [hazard ratio (HR) 0.84; 95% credibility interval (CrI) 0.71-0.98]. On subgroup analysis of individual drugs, there was no evidence of an association with viral suppression for 3TC (n = 184; HR 0.94; 95% CrI 0.73-1.15) or FTC (n = 454; HR 0.99; 95% CrI 0.80-1.19) amongst those on tenofovir-containing regimens, but we estimated a reduced rate of viral suppression for people on 3TC amongst those without tenofovir use (n = 481; HR 0.71; 95% CrI 0.54-0.90). We found no association between 3TC/FTC and detection of any new DRM (overall HR 0.92; 95% CrI 0.64-1.18), but found inconclusive evidence of a lower incidence rate of new DRMs (overall incidence rate ratio 0.69; 95% CrI 0.34-1.11). CONCLUSIONS: We did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir.


Subject(s)
Anti-HIV Agents/administration & dosage , Drug Resistance, Viral/drug effects , Emtricitabine/administration & dosage , HIV Infections/drug therapy , HIV-1/genetics , Lamivudine/administration & dosage , Tenofovir/administration & dosage , Adult , Anti-HIV Agents/pharmacology , Drug Therapy, Combination , Emtricitabine/pharmacology , Female , HIV-1/drug effects , Humans , Lamivudine/pharmacology , Male , Mutation , Tenofovir/pharmacology , Treatment Failure , United Kingdom
2.
HIV Med ; 20(2): 131-136, 2019 02.
Article in English | MEDLINE | ID: mdl-30548745

ABSTRACT

OBJECTIVES: To investigate the patterns and frequency of multiple risk behaviours (alcohol, drugs, smoking, higher risk sexual activity) among men who have sex with men (MSM) living with HIV. METHODS: Cross sectional study. RESULTS: 147 out of 819 HIV-positive MSM exhibited a high-risk phenotype (defined as >3 of smoking, excess alcohol, sexually transmitted infection and recent recreational drug use). This phenotype was associated with younger age, depressive symptoms and <90% adherence in multivariable logistic regression. CONCLUSION: In a cohort of MSM, a small, but significant proportion exhibited multiple concurrent risk behaviours.


Subject(s)
HIV Infections/drug therapy , Homosexuality, Male/psychology , Sexual Behavior/statistics & numerical data , Smoking/epidemiology , Substance-Related Disorders/epidemiology , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , HIV Infections/psychology , Health Risk Behaviors , Humans , Logistic Models , Male , Medication Adherence/psychology , Medication Adherence/statistics & numerical data , Mental Health , Middle Aged , Multivariate Analysis , Prospective Studies , Sexual Behavior/psychology , Young Adult
3.
HIV Med ; 19(5): 309-315, 2018 05.
Article in English | MEDLINE | ID: mdl-29493093

ABSTRACT

BACKGROUND: The European AIDS Clinical Society (EACS) Guidelines have since 2005 provided multidisciplinary recommendations for the care of HIV-positive persons in geographically diverse areas. GUIDELINE HIGHLIGHTS: Major revisions have been made in all sections of the 2017 Guidelines: antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Newly added are also a summary of the main changes made, and direct video links to the EACS online course on HIV Management. Recommendations on the clinical situations in which tenofovir alafenamide may be considered over tenofovir disoproxil fumarate are provided, and recommendations on which antiretrovirals can be used safely during pregnancy have been revised. Renal and bone toxicity and hepatitis C virus (HCV) treatment have been added as potential reasons for ART switches in fully virologically suppressed individuals, and dolutegravir/rilpivirine has been included as a treatment option. In contrast, dolutegravir monotherapy is not recommended. New recommendations on non-alcoholic fatty liver disease, chronic lung disease, solid organ transplantation, and prescribing in elderly are included, and human papilloma virus (HPV) vaccination recommendations have been expanded. All drug-drug interaction tables have been updated and new tables are included. Treatment options for direct-acting antivirals (DAAs) have been updated and include the latest combinations of sofosbuvir/velpatasvir/voxilaprevir and glecaprevir/pibrentasvir. Recommendations on management of DAA failure and acute HCV infection have been expanded. For treatment of tuberculosis (TB), it is underlined that intermittent treatment is contraindicated, and for resistant TB new data suggest that using a three-drug combination may be as effective as a five-drug regimen, and may reduce treatment duration from 18-24 to 6-10 months. CONCLUSIONS: Version 9.0 of the EACS Guidelines provides a holistic approach to HIV care and is translated into the six most commonly spoken languages.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , HIV Infections/drug therapy , AIDS-Related Opportunistic Infections/drug therapy , Adult , Anti-Retroviral Agents/adverse effects , Antiretroviral Therapy, Highly Active/adverse effects , Coinfection/drug therapy , Drug Interactions , Europe , Female , Humans , Male , Practice Guidelines as Topic , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Societies, Scientific
4.
J Neurovirol ; 24(3): 388-389, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29318452

ABSTRACT

Due to a production error the bottom portion of Figure 1 was omitted. The corrected figure is given below.

5.
J Neurovirol ; 24(1): 98-105, 2018 02.
Article in English | MEDLINE | ID: mdl-29280108

ABSTRACT

CINAMMON is a phase IV, open-label, single-arm, pilot study assessing maraviroc (MVC) in the central nervous system (CNS) when added to darunavir/ritonavir monotherapy (DRV/r) in virologically suppressed HIV-infected subjects. CCR5 tropic participants on DRV/r were recruited. Participants remained on DRV/r for 12 week (w) (control phase). MVC 150 mg qd was added w12-w36 (intervention phase). Lumbar puncture (LP) and neurocognitive function (Cogstate) examinations scheduled at baseline, w12 and w36; MRI before w12, again at w36. Primary endpoint was CSF inflammatory marker changes during intervention phase. Secondary endpoints included changes in NC function and MRI parameters. CSF/plasma DRV/r concentrations measured at w12 and w36, MVC at w36. Nineteen patients recruited, 15 completed (17M, 2F). Dropouts: headache (2), knee problem (could not attend, 1), personal reasons (1). Mean age (range) 45.4 years (27.2-65.1), 13/19 white, 10/19 MSM. No changes in selected CSF markers were seen w12-w36. Overall NC function did not improve w12-w36: total age adjusted z score improved by 0.27 (weighted paired t test; p = 0.11); for executive function only, age adjusted z score improved by 0.54 (p = 0.03). MRI brain parameters unchanged. DRV plasma:CSF concentration ratio unchanged between w12 (132) and w36 (112; p = 0.577, Wilcoxon signed-rank). MVC plasma:CSF concentration ratio was 35 at w36. No changes in neuroinflammatory markers seen. In this small study, addition of 24w MVC 150 mg qd to stable DRV/r monotherapy showed possible improvement in executive function with no global NC effect. Learning effect cannot be excluded. This effect should be further evaluated.


Subject(s)
Anti-HIV Agents/therapeutic use , Darunavir/therapeutic use , Executive Function/drug effects , HIV Infections/drug therapy , Maraviroc/therapeutic use , Ritonavir/therapeutic use , Adult , Aged , Biomarkers/cerebrospinal fluid , Central Nervous System/diagnostic imaging , Central Nervous System/drug effects , Central Nervous System/physiopathology , Central Nervous System/virology , Cognition/drug effects , Drug Therapy, Combination , Female , Ferritins/cerebrospinal fluid , HIV Infections/cerebrospinal fluid , HIV Infections/diagnostic imaging , HIV Infections/physiopathology , HIV-1/drug effects , HIV-1/physiology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neopterin/cerebrospinal fluid , Pilot Projects , Psychomotor Performance/drug effects , S100 Calcium Binding Protein beta Subunit/cerebrospinal fluid
6.
HIV Med ; 18(5): 370-375, 2017 05.
Article in English | MEDLINE | ID: mdl-27553526

ABSTRACT

OBJECTIVES: The objective of this paper is to summarize the outcomes of the Euroguidelines in Central and Eastern Europe (ECEE) conference held in Warsaw in February 2016. The main aim of this conference was to facilitate a discussion on European AIDS Clinical Society (EACS) guidelines implementation across the region and neighbouring countries and to present the current obstacles in benchmarking HIV care in Europe. METHODS: During a 2-day meeting, there were country-based presentations using a predefined template so as to make the data comparable and focus the discussion. Areas covered were country epidemiology, surveillance, national strategy for treatment and prevention, standards of care, access to care and treatment availability. Each participant filled in a questionnaire investigating HIV guidelines usage per country. RESULTS: In total, 16 Central and Eastern Europe (CEE) and neighbouring countries were represented at the conference: Albania, Armenia, Belarus, Croatia, Czech Republic, Estonia, Georgia, Hungary, Lithuania, Moldova, Poland, Romania, Russia, Serbia, Slovakia and Turkey. EACS guidelines version 7.1 were used in 14 (87%) countries. In 11 (69%) countries, national guidelines were available, of which eight had been recently updated. Half of the countries declared that they use World Health Organization (WHO) and Department of Health and Human Services (DHHS) guidelines, over one-third the European Centre for Disease Prevention and Control (ECDC) HIV testing guidelines and one in five the International Antiviral Society-USA (IAS-USA) Panel guidelines from 2012. CONCLUSIONS: Participants declared their will to promote the widespread use of EACS guidelines for HIV infection in the CEE region and neighbouring countries by signing the Warsaw Declaration. They also emphasized the need to increase publishing of data from national cohorts in that region.


Subject(s)
HIV Infections/diagnosis , HIV Infections/drug therapy , Practice Guidelines as Topic , Standard of Care , Europe , HIV Infections/epidemiology , HIV Infections/prevention & control , Humans , Surveys and Questionnaires
7.
Int J STD AIDS ; 28(7): 715-722, 2017 06.
Article in English | MEDLINE | ID: mdl-27510645

ABSTRACT

This study aimed to determine the prevalence of HIV neurocognitive impairment in HIV-infected men who have sex with men aged 18-50 years, using a simple battery of screening tests in routine clinical appointments. Those with suspected abnormalities were referred on for further assessment. The cohort was also followed up over time to look at evolving changes. HIV-infected participants were recruited at three clinical sites in London during from routine clinical visits. They could be clinician or self-referred and did not need to be symptomatic. They completed questionnaires on anxiety, depression, and memory. They were then screened using the Brief Neurocognitive Screen (BNCS) and International HIV Dementia Scale (IHDS). Two hundred and five HIV-infected subjects were recruited. Of these, 59 patients were excluded as having a mood disorder and two patients were excluded due to insufficient data, leaving 144 patients for analysis. One hundred and twenty-four (86.1%) had a normal composite z score (within 1 SD of mean) calculated for their scores on the three component tests of the BNCS. Twenty (13.9%) had an abnormal z score, of which seven (35%) were symptomatic and 13 (65%) asymptomatic. Current employment and previous educational level were significantly associated with BNCS scores. Of those referred onwards for diagnostic testing, only one participant was found to have impairment likely related to HIV infection. We were able to easily screen for mood disorders and cognitive impairment in routine clinical practice. We identified a high level of depression and anxiety in our cohort. Using simple screening tests in clinic and an onward referral process for further testing, we were not able to identify neurocognitive impairment in this cohort at levels consistent with published data.


Subject(s)
AIDS Dementia Complex/diagnosis , Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , HIV Infections/complications , Homosexuality, Male/psychology , Homosexuality, Male/statistics & numerical data , Mass Screening/methods , AIDS Dementia Complex/epidemiology , Adolescent , Adult , Anxiety/complications , Anxiety/epidemiology , Anxiety/psychology , Cognition Disorders/psychology , Depression/complications , Depression/epidemiology , Depression/psychology , HIV Infections/psychology , Humans , London , Male , Middle Aged , Neuropsychological Tests , Prevalence , Risk Factors , Surveys and Questionnaires
8.
HIV Med ; 18(3): 204-213, 2017 03.
Article in English | MEDLINE | ID: mdl-27476929

ABSTRACT

OBJECTIVES: Transmission of drug-resistant HIV-1 has decreased in the UK since the early 2000s. This analysis reports recent trends and characteristics of transmitted drug resistance (TDR) in the UK from 2010 to 2013. METHODS: Resistance tests conducted in antiretroviral treatment (ART)-naïve individuals between 2010 and 2013 were analysed for the presence of transmitted drug resistance mutations (TDRMs), defined as any mutations from a modified 2009 World Health Organization surveillance list, or a modified 2013 International Antiviral Society-USA list for integrase tests. Logistic regression was used to examine associations between demographics and the prevalence of TDRMs. RESULTS: TDRMs were observed in 1223 (7.5%) of 16 425 individuals; prevalence declined from 8.1% in 2010 to 6.6% in 2013 (P = 0.02). The prevalence of TDRMs was higher among men who have sex with men (MSM) compared with heterosexual men and women (8.7% versus 6.4%, respectively) with a trend for decreasing TDRMs among MSM (P = 0.008) driven by a reduction in nucleoside reverse transcriptase inhibitor (NRTI)-related mutations. The most frequently detected TDRMs were K103N (2.2%), T215 revertants (1.6%), M41L (0.9%) and L90M (0.7%). Predicted phenotypic resistance to first-line ART was highest to the nonnucleoside reverse transcriptase inhibitors (NNRTIs) rilpivirine and efavirenz (6.2% and 3.4%, respectively) but minimal to NRTIs, including tenofovir, and protease inhibitors (PIs). No major integrase TDRMs were detected among 101 individuals tested while ART-naïve. CONCLUSIONS: We observed a decrease in TDRMs in recent years. However, this was confined to the MSM population and rates remained stable in those with heterosexually acquired HIV infection. Resistance to currently recommended first-line ART, including integrase inhibitors, remained reassuringly low.


Subject(s)
Anti-Retroviral Agents/pharmacology , Disease Transmission, Infectious , Drug Resistance, Viral , HIV Infections/transmission , HIV Infections/virology , HIV-1/drug effects , Adolescent , Adult , Cohort Studies , Female , HIV-1/isolation & purification , Humans , Male , Middle Aged , Prevalence , United Kingdom/epidemiology , Young Adult
9.
S Afr Med J ; 107(1): 28-30, 2016 Dec 21.
Article in English | MEDLINE | ID: mdl-28112085

ABSTRACT

Antiretrovirals are a significant cost driver for HIV programmes. Current first-line regimens have performed well in real-life programmes, but have a low barrier to virological resistance and still carry toxicity that limits adherence. New drug developments may mean that we have access to safer, more robust and cheaper regimens, but only if the appropriate clinical trials are conducted. We briefly discuss these trials, and demonstrate the large cost savings to the South African HIV programme if these are successful.


Subject(s)
Anti-HIV Agents/economics , Antiretroviral Therapy, Highly Active/economics , Cost Savings , Drug Costs , HIV Infections/drug therapy , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , Clinical Trials as Topic , Drug Discovery , Humans , South Africa
10.
HIV Med ; 17(6): 471-8, 2016 06.
Article in English | MEDLINE | ID: mdl-26611175

ABSTRACT

OBJECTIVES: Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naïve HIV-infected subjects at the time of enrolment in the NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 study. METHODS: Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z-score using the study population sample mean and standard deviation. The primary measure was overall z-score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models. RESULTS: Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile range) age, years of education, years of known HIV infection, baseline CD4 count and baseline HIV RNA were 39 (31, 47) years, 13 (11, 17) years, 1 (0, 4) years, 344 (279, 410) cells/µL and 4.74 (4.28, 5.14) log10 HIV-1 RNA copies/mL, respectively. Forty per cent were current smokers. Factors significantly associated with poorer overall cognitive performance in multivariable models included older age, shorter duration of education, black ethnicity, lower height, and lower plasma HIV RNA. CONCLUSIONS: In this large, European-wide, ART-naïve population with relatively preserved immunity and early HIV infection, cognitive function scores at the time of ART initiation were associated with demographic and HIV-disease factors.


Subject(s)
Cognitive Dysfunction/etiology , Cognitive Dysfunction/pathology , HIV Infections/complications , HIV Infections/pathology , Adult , Anti-Retroviral Agents/administration & dosage , Europe , Female , HIV Infections/drug therapy , Humans , Male , Middle Aged , Psychological Tests
11.
J Antimicrob Chemother ; 71(4): 1056-62, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26702926

ABSTRACT

OBJECTIVES: To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir). METHODS: Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and for RT, protease and integrase (IN) genes for patients with a confirmed viral load (VL) >50 copies/mL or any single VL >500 copies/mL during or after week 32. RESULTS: A resistance test was obtained for 110/805 (13.7%) randomized participants qualifying for resistance analysis (61/401 of participants in the raltegravir arm and 49/404 of participants in the tenofovir/emtricitabine arm). No resistance-associated mutation (RAM) was observed in the tenofovir/emtricitabine plus darunavir/ritonavir arm, and all further analyses were limited to the raltegravir plus darunavir arm. In this group, 15/55 (27.3%) participants had viruses with IN RAMs (12 N155H alone, 1 N155H + Q148R, 1 F121Y and 1 Y143C), 2/53 (3.8%) with nucleotide analogue RT inhibitor RAMs (K65R, M41L) and 1/57 (1.8%) with primary protease RAM (L76V). The frequency of IN mutations at failure was significantly associated with baseline VL: 7.1% for a VL of <100,000 copies/mL, 25.0% for a VL of ≥100,000 copies/mL and <500,000 copies/mL and 53.8% for a VL of ≥500,000 copies/mL (PTREND = 0.007). Of note, 4/15 participants with IN RAM had a VL < 200 copies/mL at time of testing. CONCLUSIONS: In the NEAT001/ANRS143 trial, there was no RAM at virological failure in the standard tenofovir/emtricitabine plus darunavir/ritonavir regimen, contrasting with a rate of 29.5% (mostly IN mutations) in the raltegravir plus darunavir/ritonavir NRTI-sparing regimen. The cumulative risk of IN RAM after 96 weeks of follow-up in participants initiating ART with raltegravir plus darunavir/ritonavir was 3.9%.


Subject(s)
Antiretroviral Therapy, Highly Active , Drug Resistance, Viral , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/drug effects , Viral Load , Adult , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Female , Follow-Up Studies , HIV Infections/diagnosis , HIV-1/genetics , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Mutation , Treatment Failure , Treatment Outcome
12.
HIV Med ; 17(2): 83-8, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26548563

ABSTRACT

BACKGROUND: The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. GUIDELINE HIGHLIGHTS: The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. CONCLUSIONS: The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview.


Subject(s)
AIDS-Related Opportunistic Infections/diagnosis , HIV Infections/diagnosis , Immune Reconstitution Inflammatory Syndrome/diagnosis , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/drug therapy , Standard of Care , AIDS-Related Opportunistic Infections/drug therapy , AIDS-Related Opportunistic Infections/prevention & control , Adult , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Comorbidity , Drug Interactions , Europe/epidemiology , Female , Guidelines as Topic , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Immune Reconstitution Inflammatory Syndrome/drug therapy , Immune Reconstitution Inflammatory Syndrome/prevention & control , Male , Post-Exposure Prophylaxis , Pre-Exposure Prophylaxis , Pregnancy , Pregnancy Complications, Infectious/prevention & control , Societies, Medical , Viral Load
13.
Medicine (Baltimore) ; 94(50): e2275, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26683952

ABSTRACT

Human immunodeficiency virus type-1 (HIV-1) and human T lymphotropic virus type-1 (HTLV-1) infections have complex effects on adaptive immunity, with specific tropism for, but contrasting effects on, CD4 T lymphocytes: depletion with HIV-1, proliferation with HTLV-1. Impaired T lymphocyte function occurs early in HIV-1 infection but opportunistic infections (OIs) rarely occur in the absence of CD4 lymphopenia. In the unusual case where a HIV-1 infected individual with a high CD4 count presents with recurrent OIs, a clinician is faced with the possibility of a second underlying comorbidity. We present a case of pseudo-adult T cell leukemia/lymphoma (ATLL) in HIV-1/HTLV-1 coinfection where the individual fulfilled Shimoyama criteria for chronic ATLL and had pulmonary Mycobacterium kansasii, despite a high CD4 lymphocyte count. However, there was no evidence of clonal T-cell proliferation by T-cell receptor gene rearrangement studies nor of monoclonal HTLV-1 integration by high-throughput sequencing. Mutually beneficial interplay between HIV-1 and HTLV-1, maintaining high level HIV-1 and HTLV-1 viremia and proliferation of poorly functional CD4 cells despite chronicity of infection is a postulated mechanism. Despite good microbiological response to antimycobacterial therapy, the patient remained systemically unwell with refractory anemia. Subsequent initiation of combined antiretroviral therapy led to paradoxical resolution of CD4 T lymphocytosis as well as HIV-1 viral suppression and decreased HTLV-1 proviral load. This is proposed to be the result of attenuation of immune activation post-HIV virological control. This case illustrates the importance of screening for HTLV-1 in HIV-1 patients with appropriate clinical presentation and epidemiological risk factors and explores mechanisms for the complex interactions on HIV-1/HTLV-1 adaptive immunity.


Subject(s)
Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/immunology , HIV-1 , HTLV-I Infections/immunology , Lymphocytosis/immunology , CD4 Lymphocyte Count , Coinfection , HIV Infections/complications , HTLV-I Infections/complications , HTLV-I Infections/therapy , Humans , Lymphocytosis/complications , Lymphocytosis/therapy , Male , Middle Aged
14.
HIV Med ; 16(10): 608-19, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26111187

ABSTRACT

OBJECTIVES: Monocyte activation, endothelial dysfunction and platelet activation all potentially contribute to the increased risk of cardiovascular disease (CVD) reported in those with HIV-1 infection. To date, no study has examined how initiation of antiretroviral therapy (ART) affects markers of all three processes. We aimed to compare markers of monocyte, endothelial and platelet function between untreated HIV-positive subjects and HIV-negative controls and to examine the early effects of ART initiation on these markers. METHODS: We measured monocyte [soluble CD14 (sCD14) and sCD163], endothelial [von Willebrand factor (vWF), intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1)] and platelet [soluble P-selectin (sP-selectin), soluble CD40 ligand (sCD40L) and soluble glycoprotein VI (sGPVI)] biomarkers before and at weeks 4 and 12 post ART initiation in HIV-positive and well-matched HIV-negative controls. RESULTS: We examined 40 subjects, 25 HIV-positive subjects and 15 controls, with a median age of 34 years [interquartile range (IQR) 31, 40 years], of whom 60% were male and 47.5% Caucasian. Pre-ART, all biomarkers (monocyte, endothelial and platelet) were significantly higher in HIV-positive patients versus controls (all P < 0.05) and decreased with ART initiation, except for sCD14, which remained unchanged [median 1680 (IQR 1489, 1946) ng/mL at week 12 versus 1570 (IQR 1287, 2102) ng/mL at week 0; P = 0.7]. Although platelet activation markers reduced to levels comparable to those in controls, endothelial dysfunction markers remained elevated, as did sCD163 [at week 12, median 1005 (IQR 791, 1577) ng/mL in HIV-positive patients versus 621 (IQR 406, 700) ng/mL in controls; P < 0.0001]. CONCLUSIONS: ART initiation resulted in reductions in levels of CVD-associated biomarkers; however, although they improved, markers of endothelial dysfunction and monocyte activation remained elevated. How these persistent abnormalities affect CVD risk in HIV infection remains to be determined.


Subject(s)
Antiretroviral Therapy, Highly Active/adverse effects , Blood Platelets/drug effects , Endothelium, Vascular/drug effects , HIV Infections/drug therapy , HIV-1 , Monocytes/drug effects , Adult , Biomarkers/blood , Blood Platelets/metabolism , Blood Platelets/physiology , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/physiopathology , Case-Control Studies , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Female , HIV Infections/blood , HIV Infections/physiopathology , Humans , Male , Middle Aged , Monocytes/metabolism , Monocytes/physiology
15.
HIV Med ; 16(8): 457-67, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25944246

ABSTRACT

HIV-positive patients are at increased risk of developing chronic kidney disease. Although guidelines recommend regular monitoring of renal function in individuals living with HIV, the optimal frequency remains to be defined. In this review, we discuss the renal syndromes that may be identified at an earlier stage via routine assessment of kidney function, and provide guidance in terms of the frequency of monitoring, the most useful tests to perform, and their clinical significance. Specifically, we address whether annual monitoring of kidney function is appropriate for the majority of HIV-positive patients.


Subject(s)
Acute Kidney Injury/etiology , HIV Infections/complications , Renal Insufficiency, Chronic/etiology , Acute Kidney Injury/diagnosis , Albuminuria/diagnosis , Algorithms , Glomerular Filtration Rate , Hematuria/diagnosis , Humans , Proteinuria/diagnosis , Renal Insufficiency, Chronic/diagnosis , Risk Factors
16.
Vestn Oftalmol ; 131(1): 50-57, 2015.
Article in Russian | MEDLINE | ID: mdl-25872387

ABSTRACT

OBJECTIVE: To study the influence of C. trachomatis infection on proliferative vitreoretinopathy (PVR) stimulation and development in an experimental model. MATERIAL AND METHODS: Intravitreal C. trachomatis injection was performed in 17 rabbits (right eyes) out of which 8 developed minimal chlamydial damage (1 was further subjected to histopathological examination with pathogen detection in ocular structures and other 7 were included in the study group). The control group consisted of 7 rabbits with no laboratory evidence of chlamydial infection. PVR was induced by 4 peripheral retinal punctures with a 19 G needle. Follow-up methods included ophthalmoscopy, ultrasonography, and PVR grading according to the Fastenberg classification. Histopathological examination, supplemented with pathogen detection by direct immunofluorescence in the study group, was performed at weeks 7 and 20. RESULTS: PVR rate and severity were higher in the study group as compared with the controls (5 out of 7 rabbits, grade 2-4 vs. 2 out of 7 rabbits, grade 0-1, p<0.01). In the study group, histopathological examination performed before and after the induction of PVR revealed a pronounced lymphocyte and macrophage infiltration, characteristic of infectious inflammation. Similarly, extra- and intracellular chlamydial inclusions could be found in the retina and/or zones of proliferation throughout the whole study period. Inflammation signs (including those of proliferation) were reliably less significant in the controls. CONCLUSION: C. trachomatis infection of the posterior segment contributes to PVR development due to associated chronic inflammation.


Subject(s)
Chlamydia Infections/complications , Chlamydia trachomatis/isolation & purification , Eye Infections, Bacterial/complications , Retina/microbiology , Vitreoretinopathy, Proliferative/etiology , Vitreous Body/microbiology , Animals , Antibodies, Bacterial/analysis , Chlamydia Infections/microbiology , Chlamydia Infections/pathology , Chlamydia trachomatis/immunology , Disease Models, Animal , Eye Infections, Bacterial/microbiology , Eye Infections, Bacterial/pathology , Fluorescent Antibody Technique, Direct , Follow-Up Studies , Rabbits , Retina/pathology , Vitreoretinopathy, Proliferative/microbiology , Vitreoretinopathy, Proliferative/pathology , Vitreous Body/pathology
17.
Int J STD AIDS ; 26(2): 128-32, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24759562

ABSTRACT

Studies have suggested CD8 lymphocytes may be a possible marker for inflammation, which is believed to be a contributing factor to neurocognitive impairment. Individuals enrolled in the MSM Neurocog Study were analysed. Those with depression, anxiety or mood disorders were excluded. Individuals with neurocognitive impairment were identified using the Brief NeuroCognitive Screen and compared to those with normal scores. CD4 and CD8 T cell values and CD4:CD8 ratios were compared between groups. In all, 144 men, aged 18-50 years, were included in the analysis. Twenty were diagnosed with neurocognitive impairment. We were unable to identify any significant difference between current, nadir or peak CD4 and CD8 counts. CD4:CD8 ratios and CD4:CD8 ratio inversion (<1) were also found to be similar between both groups. However, neurocognitive impairment subjects were 8% more likely to have inversion of CD4:CD8 ratio and higher median peak CD8 cell counts reported compared to non-impaired subjects. Analysis of data from the MSM Neurocog Study, demonstrated trends in peripheral CD8 counts and CD4:CD8 ratios. However, we are unable to demonstrate any significant benefit. Plasma biomarkers of neurocognitive impairment in HIV-infected subjects would be of great benefit over current methods of invasive CSF analysis and technical neuroimaging used in the diagnosis of neurocognitive impairment. Future, prospective, longitudinal work with large numbers of neurocognitive impairment subjects is required to further investigate the role of peripheral CD8 T cells as markers of neurocognitive impairment.


Subject(s)
CD8-Positive T-Lymphocytes/pathology , Cognition Disorders/pathology , HIV Infections/complications , Homosexuality, Male , Adolescent , Adult , CD4-CD8 Ratio , Humans , London , Male , Middle Aged , Neuropsychological Tests , Retrospective Studies , Risk Factors , Surveys and Questionnaires , Young Adult
19.
AIDS Care ; 26(2): 160-8, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23869661

ABSTRACT

With increasingly successful management of HIV, focus has shifted away from AIDS-related complications to other chronic co-morbidities. For HIV-related cognitive problems, the true aetiopathogenesis and epidemiology remains unclear. Rather than a systematic review, this paper presents the challenges and the opportunities we faced in establishing our own clinical service. Papers were identified using Pubmed and the terms "screening", "HIV" and "neurocognitive". This article covers the background of HIV-associated neurocognitive disorders (HAND) with a focus on HIV-related neurocognitive impairment (NCI), detailing classification, prevalence, diagnostic categories and diagnostic uncertainties. Screening is discussed, including a comparison of the available screening tools for cognitive deficits in HIV-infected patients and the importance of practice effects. Discussed also are the normal ranges and the lack thereof and potential investigations for those found to have impairments. We conclude by discussing the role of NCI screening in routine clinical care at the current time.


Subject(s)
AIDS Dementia Complex/diagnosis , HIV Seropositivity/complications , Mass Screening , AIDS Dementia Complex/drug therapy , AIDS Dementia Complex/epidemiology , Activities of Daily Living , Comorbidity , Disability Evaluation , Female , HIV Seropositivity/epidemiology , HIV Seropositivity/psychology , Humans , Male , Mass Screening/methods , Neuropsychological Tests , Prevalence , Program Evaluation , Quality of Life , Socioeconomic Factors
20.
HIV Med ; 15(5): 257-68, 2014 May.
Article in English | MEDLINE | ID: mdl-24351025

ABSTRACT

This review looks at the evidence for potential and theoretical risks of combining antiretroviral treatment with drugs prescribed for cardiovascular disease and diabetes. These conditions are common in the HIV-infected population as a result of ageing and the increased risk associated with both HIV infection and antiretroviral intake.


Subject(s)
Cardiovascular Diseases/drug therapy , Diabetes Mellitus/drug therapy , HIV Infections/complications , Aged , Anti-Retroviral Agents/therapeutic use , Antihypertensive Agents/therapeutic use , Drug Interactions , Drug Therapy, Combination , HIV Infections/drug therapy , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypoglycemic Agents/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use
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