CD81 expression in peripheral blood lymphocytes before and after treatment with interferon and ribavirin in HIV/HCV coinfected patients

Background

CD81 is expressed on lymphocytes and confers HCV viral infectivity support. The aim of our study was to quantify CD81 expression in peripheral blood B‐ and T‐cells of HCV/HIV‐coinfected patients and healthy subjects to examine its association with several HCV virological characteristics and the therapeutic responsiveness to HCV antiviral treatment.

Methods

We carried out a cross‐sectional study on 122 naïve patients. For a duration of 48 weeks, 24 out of 122 patients underwent HCV antiviral therapy with interferon (IFN)‐α and ribavirin. T‐ and B‐cell subsets were analysed by flow cytometry.

Results

We found that HIV/HCV coinfected patients with HCV‐RNA ≥850 000 IU/mL had lower values of %CD19+CD81‐CD62L+ and %CD19+CD62L+; and higher values of CD19+CD81+CD62L− and CD19+CD81+ percentages and absolute counts than patients with HCV‐RNA <850 000 IU/mL. Similarly, HIV/HCV coinfected patients with the genotype 1 had lower values of %CD19+CD81−CD62L+ and higher values of CD3+CD81+CD62L− and CD3+CD81+ percentages and absolute counts than patients without genotype 1. Moreover, we found that HIV/HCV coinfected patients had higher values of %CD19+HLA‐DR+CD25+, %CD19+CD40+CD25+ and %CD19+CD25+ than healthy control patients. When we studied the B‐ and T‐cell subset kinetics of 24 HIV/HCV coinfected patients on HCV antiviral therapy, we found a significant decrease in CD3+CD81+and CD3+CD81+CD62L− subsets and a significant increase in CD3+CD62L+ and CD3+CD81+CD62L+ percentages and absolute counts, but the variation in these markers disappeared several months after stopping the treatment.

Conclusions

We observed a different pattern of CD81 T‐cell and B‐cell levels in naïve HIV/HCV coinfected patients according to HCV virological status and their subsequent variations during HCV antiviral treatment. CD81 expression might influence HCV pathogenesis and response to HCV antiviral treatment.

     

Low plasma levels of dehydroepiandrosterone sulphate in HIV-positive patients coinfected with hepatitis C virus

Objectives

To evaluate plasma levels of dehydroepiandrosterone sulphate (DHEAS) in a cohort of HIV‐infected patients and to analyse factors associated with DHEAS levels.

Methods

We conducted a cross‐sectional survey in the Nîmes University Hospital cohort of HIV‐infected patients in south‐eastern France. All HIV‐infected patients with at least one outpatient visit between 1 January and 1 September 2002 were included in the study. Sociodemographic, clinical, therapeutic, immuno‐virological and plasma DHEAS level data were collected during this period. Hepatitis C virus (HCV) coinfection was defined as the presence of HCV antibody with positive RNA. To identify factors associated with plasma DHEAS levels, Spearman's rank correlation and univariate and multivariate linear regression analyses were used.

Results

The DHEAS plasma level was measured in 137 patients (104 men and 33 women), 37 (27.0%) of whom were HCV coinfected. The median age of the patients was 39.1 years [interquartile range (IQR): 34.9–48.7] for women and 41.8 years (36.5–47.7) for men. The median DHEAS level was 5.5 μmol/L (IQR: 2.3–8.8) for the whole sample of 137 patients, and was lower in women (2.4 μmol/L; 1.5–6.6) than in men (6.1 μmol/L; 2.5–9.0) (P<0.01), and lower in patients coinfected with HCV (2.1 μmol/L; 0.6–6.7) than in those not coinfected (6.6 μmol/L; 3.0–9.1) (P<0.01). Of all prognostic factors studied in the variance covariance analysis, three factors were associated with DHEAS: age, gender and HCV coinfection. Subgroup analysis revealed that the age‐adjusted mean of the DHEAS level was lower in HCV coinfected patients for both women (1.3±1.1 μmol/L) and men (4.0±0.7 μmol/L), compared with patients not HCV coinfected (women, 5.3±0.7 μmol/L; men, 7.2±0.4 μmol/L) (P<0.01).

Conclusions

This is the first report of the determination of DHEAS plasma levels in HIV/HCV coinfected patients. When age and sex were taken into account, the DHEAS plasma level was found to be significantly lower in HCV coinfected patients. To date, the pathophysiology of such findings is unknown.

     

Persistently normal alanine aminotransferase levels in HIV/HCV-coinfected patients: the role of steatosis

Objective

The frequency and significance of, and liver biopsy findings associated with, a persistently normal alanine aminotransferase (ALT) level in HIV/hepatitis C virus (HCV)‐coinfected patients are poorly characterized. We analysed factors associated with persistently normal ALT levels, defined as at least three consecutive normal ALT values over a 6‐month period, in a group of 381 HIV/HCV‐coinfected patients.

Methods

Patients were categorized into two groups according to ALT values: group 1, patients with persistently normal ALT levels; and group 2, patients with elevated ALT values. Possible interactions with host factors, HIV and HCV viral factors, antiretroviral treatment and histological features were examined.

Results

Thirty‐six patients (9.4%) had persistently normal ALT levels. None of the 36 patients had cirrhosis. Seven patients (19.4%) had a METAVIR fibrosis score of F3. In multivariate analysis, a lower mean METAVIR inflammation score [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.28–0.89; P=0.017], the absence of steatosis (OR 0.43, 95% CI 0.20–0.90; P=0.026) and HCV genotype 4 infection (OR 2.81, 95% CI 1.15–6.68; P=0.023) were associated with persistently normal ALT levels.

Conclusion

The slower progression of chronic hepatitis in patients with persistently normal ALT levels could be related, in part, to a lower frequency of steatosis

     

Food insecurity may lead to incomplete HIV viral suppression and less immune reconstitution among HIV/hepatitis C virus‐coinfected people

Objectives

The aim of this study was to determine the impact of food insecurity (FI) on HIV viral load and CD4 count among people coinfected with HIV and hepatitis C virus (HCV).

Methods

This study was conducted using data from the Food Security & HIV‐HCV Sub‐Study of the Canadian Co‐Infection Cohort study. FI was measured using the adult scale of Health Canada's Household Food Security Survey Module and was classified into three categories: food security, moderate food insecurity and severe food insecurity. The association between FI, HIV viral load, and CD4 count was assessed using a stabilized inverse probability weighted marginal structural model.

Results

A total of 725 HIV/HCV‐coinfected people with 1973 person‐visits over 3 years of follow‐up contributed to this study. At baseline, 23% of participants experienced moderate food insecurity and 34% experienced severe food insecurity. The proportion of people with undetectable HIV viral load was 75% and the median CD4 count was 460 [interquartile range (IQR): 300–665] cells/μL. People experiencing severe food insecurity had 1.47 times [95% confidence interval (CI): 1.14, 1.88] the risk of having detectable HIV viral load and a 0.91‐fold (95% CI: 0.84, 0.98) increase in CD4 count compared with people who were food secure.

Conclusions

These findings provide evidence of the negative impact of food insecurity on HIV viral load and CD4 count among HIV/HCV‐coinfected people.

     

HIV/hepatitis C virus and HIV/hepatitis B virus coinfections protect against antiretroviral-related hyperlipidaemia

Introduction

Hyperlipidaemia is a recognized complication of HIV antiretroviral therapy. The interactions among HIV, viral hepatitis, antiretroviral therapies and lipids are poorly understood.

Methods

Ontario HIV Treatment Network Cohort Study participants with at least one lipid level after highly active antiretroviral therapy (HAART) initiation were assessed. Hepatitis B virus (HBV)‐ and hepatitis C virus (HCV)‐coinfected patients were identified by serology or chart review. HCV antiviral recipients, diabetics and those on lipid‐lowering drugs at baseline were excluded from the study. Factors associated with a decreased risk of grade 3 or 4 hyperlipidaemia or lipid‐lowering drug use were assessed by multivariate logistic regression.

Results

A total of 1587 HIV‐monoinfected, 190 HIV/HBV‐coinfected and 255 HIV/HCV‐coinfected patients were evaluated. Most were male (85–92% for the 3 groups evaluated: HIV, HIV/HBV, HIV/HCV). The median [interquartile range (IQR)] age at HAART initiation was 48 (44–56) years and was similar between groups. The median (IQR) CD4 count at HAART initiation was 245 (120–370) cells/μL in HIV‐monoinfected participants, 195 (110–330) cells/μL in HIV/HBV‐coinfected participants and 268 (140–409) cells/μL in HIV/HCV‐coinfected participants. Factors associated with a decreased risk of grade 3 or 4 hyperlipidaemia or lipid‐lowering drug use included HIV/HCV coinfection [odds ratio (OR) 0.46; 95% confidence interval (CI) 0.34, 0.61; P<0.0001], HIV/HBV coinfection (OR 0.74; 95% CI 0.55, 0.99; P=0.04), year of starting HAART after 2004 vs. 1997 or earlier (OR 0.37; 95% CI 0.29, 0.48; P<0.0001) and year of starting HAART between 1998 and 2003 vs. 1997 or earlier (OR 0.75; 95% CI 0.61, 0.92; P<0.01). Factors associated with increased risk included age (OR 1.55; 95% CI 1.39, 1.72; per 10 years, P<0.0001) and male gender (OR 1.84; 95% CI 1.36, 2.48; P<0.0001).

Conclusions

HIV/HCV and to a lesser extent HIV/HBV coinfections are protective against HAART‐related hyperlipidaemia.     

Oral candidiasis and seborrheic dermatitis in HIV-infected patients on highly active antiretroviral therapy

Background

Mucocutaneous manifestations such as oral candidiasis (OC) and seborrheic dermatitis (SD) are very common HIV‐related opportunistic events and are usually initial markers of immunodeficiency.

Aim

The purpose of this study was to evaluate the efficacy of highly active antiretroviral therapy (HAART) in the regression of HIV‐associated OC and SD.

Methods

In a prospective study, 120 HIV‐infected patients with OC and SD were divided into two groups: HAART‐treated patients (group 1, n=76) and non‐HAART‐treated patients (group 2, n=44). Non‐HAART‐treated patients were given antimicrobial therapy. Study subjects were matched for sex, age, risk, and stage of HIV infection. The results were analysed by χ² test and the Kaplan‐Meier method.

Results

At baseline, OC was evident in 59 (77.7%) of the HAART‐treated patients and in 34 (77.3%) of the non‐HAART‐treated patients, while SD was present in 19 (25.0%) of the HAART‐treated patients and in 17 (38.6%) of the non‐HAART‐treated patients. After a median follow‐up period of 22 months, regression of OC and SD occurred in 49 (83.1%) and 16 (84.2%) of the HAART‐treated patients, respectively. In the control group, regression of OC and SD occurred in only five (14.7%) and seven (41.2%) patients, respectively, during the same period.

Conclusions

HAART showed greater efficacy than standard antimicrobial therapy for the treatment of OC and SD in HIV‐infected patients.

     

Rates of sustained virological response 12 weeks after the scheduled end of direct‐acting antiviral (DAA)‐based hepatitis C virus (HCV) therapy from the National German HCV registry: does HIV coinfection impair the response to DAA combination therapy?

Objectives

The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)‐coinfected and HCV‐monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV‐infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany.

Methods

Data acquired from the Deutsches Hepatitis C‐Registry were analysed. A total of 5657 HCV‐monoinfected subjects and 488 HIV/HCV‐coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients.

Results

HIV/HCV‐coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P < 0.001) and younger than HCV‐monoinfected subjects (46.5 ± 9 vs. 53.8 ± 12.5 years, respectively; P < 0.001). The CD4 blood cell count was > 350 cells/μL in 63.1% of HIV‐positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV‐monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV‐monoinfected and HIV/HCV‐coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P = 0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups).

Conclusions

We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration.

     

Association of hypocholesterolaemia with hepatitis C virus infection in HIV-infected people

Objective

To study the impact of hepatitis C virus (HCV) status on serum cholesterol levels in HIV‐infected patients.

Methods

We retrospectively analysed data from the 881 participants of the Veterans Ageing Cohort 3 Site Study. Four different models were constructed using total cholesterol, low‐density lipid (LDL) cholesterol, high‐density lipid (HDL) cholesterol and triglycerides as dependent variables. The relevant covariates included HCV antibody status, HIV medication class, CD4 count, HIV viral load, glucose level, lipid‐lowering drug use, gender, race, age, liver function test results, ethanol use, drug use, and HIV exposure category. Variables excluded from the final model included niacin use, gender, race, age, current ethanol use, and HIV exposure category.

Results

Of the 881 HIV‐positive patients enrolled in the study, 700 (79%) were screened for HCV antibody, with 300 (42.8%) HCV antibody positive and 400 (57.2%) HCV antibody negative. A positive HCV antibody status was independently associated with lower total cholesterol levels (P=0.001) and LDL cholesterol levels (P<0.001) but not with lower HDL cholesterol or triglyceride levels. HCV‐positive patients had predicted LDL levels 19 mg/dL lower than those of HCV‐negative subjects. HCV infection was also associated with a decreased use of lipid‐lowering medication, and protease inhibitor use was associated with increased LDL and total cholesterol levels.

Conclusions

HCV infection has been associated with lower cholesterol levels in HIV‐negative individuals, and the same appears to be true with HIV‐infected patients. This is an interesting finding given that HCV particles bind to LDL receptors in vitro and also because HCV–lipid interactions appear to be important in the HCV replication cycle.

     

Causes of death among HIV-infected patients in the era of highly active antiretroviral therapy,Bordeaux, France, 1998-1999

Objectives

To describe the causes of death in HIV‐infected patients in the era of highly active antiretroviral therapy (HAART).

Method

A retrospective survey conducted in Bordeaux, France. Medical records of all deaths that had occurred in 1998 and 1999 amongst patients followed within the Aquitaine cohort were reviewed by the same physician. Immediate and underlying causes of death were described, taking into account the morbidity at the time of death.

Results

Sixty‐six deaths occurred in 1998, and 41 in 1999. Sixty‐seven per cent of deceased patients were male. Median age at time of death was 43 years (range 25–71), median CD4 was 162 cells/µL (0–957); 28% of patients had a CD4 count > 200 cells/µL and 7% plasma viral load < 500 HIV‐RNA copies/mL. Amongst morbidity present at the time of death, there were 23 bacterial infections, 16 non‐Hodgkin's lymphomas, 16 cirrhoses, 15 non HIV‐related malignancies, 13 central nervous system diseases and 10 myocardiopathies. The main immediate causes of death were: multiple organ failure (21%), coma (18%), septic shock (15%) and acute respiratory failure (14%). Underlying causes of death were AIDS‐defining events (48%), non AIDS HIV‐related infection (3%), hepatitis B‐ or C‐associated cirrhosis (14%), non HIV‐related malignancies (11%), cardiovascular events (10%), suicide and overdose (6%), treatment‐related fatalities (4%), injury (2%) and unknown (2%). Patients dying from AIDS‐related events were more often female, had a lower CD4 count, a higher level of HIV‐RNA, a shorter history of HIV infection and were less often coinfected with hepatitis B and C viruses than those dying from other underlying causes.

Conclusions

AIDS‐related events are no longer the major causes of death of HIV‐infected patients in the era of HAART. This evolving mortality pattern justifies an adaptation of both the epidemiological surveillance and the clinical monitoring of HIV‐infected patients.

     

Coinfection with hepatitis C virus,oxidative stress and antioxidant status in HIV‐positive drug users in Miami*

Background

The pathogenesis of HIV/hepatitis C virus (HCV) coinfection is poorly understood. We examined markers of oxidative stress, plasma antioxidants and liver disease in HIV/HCV‐coinfected and HIV‐monoinfected adults.

Methods

Demographics, medical history, and proof of infection with HIV, hepatitis A virus (HAV), hepatitis B virus (HBV) and HCV were obtained. HIV viral load, CD4 cell count, complete blood count (CBC), complete metabolic panel, lipid profile, and plasma concentrations of zinc, selenium, and vitamins A and E were determined. Malondialdehyde (MDA) and glutathione peroxidase concentrations were obtained as measures of oxidative stress. Aminotransferase to platelet ratio index (APRI) and fibrosis index (FIB‐4) markers were calculated.

Results

Significant differences were found between HIV/HCV‐coinfected and HIV‐monoinfected participants in levels of alanine aminotransferase (ALT) (mean±standard deviation: 51.4±50.6 vs. 31.9±43.1 U/L, respectively; P=0.014), aspartate aminotransferase (AST) (56.2±40.9 vs. 34.4±30.2 U/L; P<0.001), APRI (0.52±0.37 vs. 0.255±0.145; P=0.0001), FIB‐4 (1.64±.0.91 vs. 1.03±0.11; P=0.0015) and plasma albumin (3.74±0.65 vs. 3.94±0.52 g/dL; P=0.038). There were no significant differences in CD4 cell count, HIV viral load or antiretroviral therapy (ART) between groups. Mean MDA was significantly higher (1.897±0.835 vs. 1.344± 0.223 nmol/mL, respectively; P=0.006) and plasma antioxidant concentrations were significantly lower [vitamin A, 39.5 ± 14.1 vs. 52.4±16.2 μg/dL, respectively (P=0.0004); vitamin E, 8.29±2.1 vs. 9.89±4.5 μg/mL (P=0.043); zinc, 0.61±0.14 vs. 0.67±0.15 mg/L (P=0.016)] in the HIV/HCV‐coinfected participants than in the HIV‐monoinfected participants, and these differences remained significant after adjusting for age, gender, CD4 cell count, HIV viral load, injecting drug use and race. There were no significant differences in glutathione peroxidase concentration, selenium concentration, body mass index (BMI), alcohol use or tobacco use between groups. Glutathione peroxidase concentration significantly increased as liver disease advanced, as measured by APRI (β=0.00118; P=0.0082) and FIB‐4 (β=0.0029; P=0.0177). Vitamin A concentration significantly decreased (β=?0.00581; P=0.0417) as APRI increased.

Conclusion

HIV/HCV coinfection is associated with increased oxidative stress and decreased plasma antioxidant concentrations compared with HIV monoinfection. Research is needed to determine whether antioxidant supplementation delays liver disease in HIV/HCV coinfection.

     

The creation of a large UK-based multicentre cohort of HIV-infected individuals: The UK Collaborative HIV Cohort (UK CHIC) Study

Objectives

This paper describes the development of the UK Collaborative HIV Cohort (CHIC) Study. The aim of the study is to collate routinely collected data on HIV‐infected individuals attending one of seven clinical centres in the UK since 1 January 1996, with the objectives of describing changes over time in the frequency of AIDS‐defining illnesses, describing the uptake of and response to highly active antiretroviral therapy (HAART), and identifying factors associated with virological and immunological responses to HAART.

Methods

By December 2002, demographic, clinical and laboratory data had been collected on HIV‐positive patients seen at six of the seven HIV centres. Missing and inconsistent data had been investigated and the datasets audited. Records identified as relating to the same patient had been merged, and cross‐checks made with UK death registers to improve the accuracy of death reporting.

Results

The cohort currently contains information on 13 833 individuals. Eighty‐two per cent of the cohort are male, and the median age was 34 years at first follow‐up. The main risk factors for HIV infection have been determined as sex between men (63%) and sex between men and women (24%). Twenty‐five per cent of the cohort are known to have developed AIDS, and 8% have died.

Conclusions

The UK CHIC Study provides important information on the status of individuals infected with HIV in the UK, and provides a means to study the response to HAART and to monitor changes in the clinical event and death rates that have occurred since the introduction of HAART in the UK.

     

T-lymphocyte populations in hepatitis C and HIV co-infected patients treated with interferon-alfa-2a and ribavirin

Objective

The effects on T‐lymphocyte populations of two interferon‐alfa‐2a (IFN) regimens associated with ribavirin were evaluated in 36 HCV‐HIV co‐infected patients with chronic hepatitis C, T‐CD4 cell count > 250 cells/µL and a plasma viral load of < 10 000 HIV RNA copies/mL.

Methods

Patients were given IFN for 48 weeks. Group A (18 patients) received 6 mega units (MU) subcutaneously three times a week for 24 weeks, then 3 MU three times a week for the last 24 weeks. Group B (18 patients) received 9 MU daily for 2 weeks, 3 MU daily for 22 weeks, then 3 MU three times a week for the last 24 weeks. Serum HCV RNA was evaluated at weeks 12 and 72. Ribavirin was added at week 16 for virologic nonresponders at week 12. CD3, CD3 CD4, CD3 CD8, CD3 CD4 human leucocyte antigen (HLA)‐DR and CD3 CD8 HLA‐DR lymphocyte subsets were evaluated before, during and after treatment by cytofluorometry. Controls were healthy and HCV mono‐infected patients.

Results

CD3 CD4 and CD3 CD8 T‐cells counts were both impaired during anti‐HCV therapy, but returned to baseline value after treatment completion. Lymphopenia concerned mainly CD8 T‐cells, the percentage of which decreased, whereas that of CD4 increased. Three patients displayed reversible CD4 lymphopenia < 200 cells/µL. HIV infection at inclusion was responsible for higher CD3 CD8 HLA‐DR T‐cell percentages in co‐infected patients than in healthy and HCV mono‐infected subjects. T‐cell sequestration in lymphoid tissues and enhanced apoptosis may account for lymphopenia.

Conclusion

High‐dosed IFN anti‐HCV therapy induced only moderate and transient CD4 lymphopenia in HIV co‐infected patients.

     

Opportunistic infections and organ‐specific diseases in HIV‐1‐infected children: a cohort study (1990–2006)

Objectives

Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV infection in children, but there are few studies in the literature about the incidence of clinical manifestations after HAART in this population, compared with adults. The aim of this study was to describe the influence of the widespread use of HAART on the development of opportunistic infections and organ‐specific diseases in HIV‐infected children.

Methods

An observational study of a cohort of 366 vertically HIV‐infected children followed from 1990 to 2006 was carried out. According to the main antiretroviral protocol used, three calendar periods (CPs) were defined and compared: CP1 (1990–1996: no patients on HAART), CP2 (1997–1999: <60% on HAART) and CP3 (2000–2006: >60% on HAART).

Results

Children experienced a progressive increase in CD4 T cell count (P<0.05) and a decrease in HIV viral load from 1996 onwards (P<0.05). Similarly, rates of death, AIDS, opportunistic infections (bacteraemia, candidosis, cryptosporidiosis and bacterial pneumonia) and organ‐specific diseases (wasting syndrome, thrombocytopenia, cardiomyopathy, lymphoid interstitial pneumonia and HIV‐associated encephalopathy) were lower in CP2 and CP3 than in CP1.

Conclusions

This study provides evidence of improved clinical outcomes in HIV‐infected children over time and shows that mortality, AIDS, opportunistic infections and organ‐specific diseases declined as HAART was progressively instituted in this population.

     

Later onset of herpes zoster-associated immune reconstitution inflammatory syndrome

Objectives

The aim of the study was to determine whether immune reconstitution inflammatory syndrome (IRIS) associated with herpes zoster occurs on a different time frame from other instances of IRIS.

Methods

Statistical analysis of onset times of herpes zoster‐associated IRIS and other cases of IRIS was carried out in a retrospective cohort starting antiretroviral therapy at advanced stages of HIV infection.

Results

Herpes zoster‐associated IRIS was significantly more frequent after the first 3 months of successful highly active antiretroviral therapy (HAART), than other instances of IRIS (IRIS associated with tuberculosis, Mycobacterium avium complex, Kaposi's sarcoma, etc.) which mainly occurred during the first 3 months of treatment.

Conclusions

The characteristic onset time pattern of herpes zoster‐associated IRIS, coincident with the second phase of immune recovery under HAART, suggests that the immune recovery events underlying herpes zoster‐associated IRIS are different from those underlying other types of IRIS. Our findings may be useful in improving the follow‐up of individuals who start HAART at an advanced stage of HIV infection.

     

Superior virological response to boosted protease inhibitor-based highly active antiretroviral therapy in an observational treatment programme

Background

The use of boosted protease inhibitor (PI)‐based antiretroviral therapy has become increasingly recommended in international HIV treatment consensus guidelines based on the results of randomized clinical trials. However, the impact of this new treatment strategy has not yet been evaluated in community‐treated cohorts.

Methods

We evaluated baseline characteristics and plasma HIV RNA responses to unboosted and boosted PI‐based highly active antiretroviral therapy (HAART) among antiretroviral‐naïve HIV‐infected patients in British Columbia, Canada who initiated HAART between August 1997 and September 2003 and who were followed until September 2004. We evaluated time to HIV‐1 RNA suppression (<500 HIV‐1 RNA copies/mL) and HIV‐1 RNA rebound (≥500 copies/mL), while stratifying patients into those that received boosted and unboosted PI‐based HAART as the initial regimen, using Kaplan–Meier methods and Cox proportional hazards regression.

Results

During the study period, 682 patients initiated therapy with unboosted PI and 320 individuals initiated HAART with a boosted PI. Those who initiated therapy with a boosted PI were more likely to have a CD4 cell count <200 cells/μL and to have a plasma HIV RNA>100 000 copies/mL, and to have AIDS at baseline (all P<0.001). However, when we examined virological response rates, those who initiated HAART with a boosted PI achieved more rapid virological suppression [relative hazard 1.26, 95% confidence interval (CI) 1.06–1.51, P=0.010].

Conclusions

Patients prescribed boosted PIs achieved superior virological response rates despite baseline factors that have been associated with inferior virological responses to HAART. Despite the inherent limitations of observational studies which require this study be interpreted with caution, these findings support the use of boosted PIs for initial HAART therapy.

     

CD4 percentage is an independent predictor of survival in patients starting antiretroviral therapy with absolute CD4 cell counts between 200 and 350 cells/microL

Objective

To determine the prognostic value of baseline CD4 percentage in terms of patient survival in comparison to absolute CD4 cell counts for HIV‐positive patients initiating highly active antiretroviral therapy (HAART).

Methods

A population‐based cohort study of 1623 antiretroviral therapy‐naïve HIV‐positive individuals who initiated HAART between 1 August 1996 and 30 June 2002 was conducted. Cumulative mortality rates were estimated using Kaplan–Meier methods. Cox proportional hazards regression was used to model the effect of baseline CD4 strata and CD4 percentage strata and other prognostic variables on survival. A subgroup analysis was conducted on 417 AIDS‐free subjects with baseline CD4 counts between 200 and 350 cells/μL.

Results

In multivariate models, low CD4 percentages were associated with increased risk of death [CD4%<5, relative hazard (RH)=4.46; CD4% 5–14, RH=2.43; P<0.01 for both] when compared with those subjects with an initial CD4 fraction of 15% or greater, but had less predictive value than absolute CD4 counts. In subgroup analyses where absolute CD4 strata were not associated with mortality, a baseline CD4 fraction below 15% [RH=2.71; 95% confidence interval (CI) 1.20–6.10], poor adherence to therapy and baseline viral load >100 000 HIV‐1 RNA copies/mL were associated with an increased risk of death.

Conclusion

CD4 percentages below 15% are independent predictors of mortality in AIDS‐free patients starting HAART, including those with CD4 counts between 200 and 350 cells/μL. CD4 percentage should be considered for inclusion in guidelines used to determine when to start therapy.

     

Hospitalization risk following initiation of highly active antiretroviral therapy

Objectives

While highly active antiretroviral therapy (HAART) decreases long‐term morbidity and mortality, its short‐term effect on hospitalization rates is unknown. The primary objective of this study was to determine hospitalization rates over time in the year after HAART initiation for virological responders and nonresponders.

Methods

Hospitalizations among 1327 HAART‐naïve subjects in an urban HIV clinic in 1997–2007 were examined before and after HAART initiation. Hospitalization rates were stratified by virological responders (≥1 log₁₀ decrease in HIV‐1 RNA within 6 months after HAART initiation) and nonresponders. Causes were determined through International Classification of Diseases, 9th Revision (ICD‐9) codes and chart review. Multivariate negative binomial regression was used to assess factors associated with hospitalization.

Results

During the first 45 days after HAART initiation, the hospitalization rate of responders was similar to their pre‐HAART baseline rate [75.1 vs. 78.8/100 person‐years (PY)] and to the hospitalization rate of nonresponders during the first 45 days (79.4/100 PY). The hospitalization rate of responders fell significantly between 45 and 90 days after HAART initiation and reached a plateau at approximately 45/100 PY from 91 to 365 days after HAART initiation. Significant decreases were seen in hospitalizations for opportunistic and nonopportunistic infections.

Conclusions

The first substantial clinical benefit from HAART may be realized by 90 days after HAART initiation; providers should keep close vigilance at least until this time.

     

Assessing limiting factors to the acceptance of antiretroviral therapy in a large cohort of injecting drug users

Objective

A comprehensive questionnaire was designed to assess the knowledge and understanding of injecting drug users (IDUs) regarding their HIV disease, and to determine any factors that may increase the acceptance of antiretroviral therapy (ART) by this group.

Results

Twenty percent of the total IDU cohort attending the GUIDE (GenitoUrinary Medicine and Infectious Diseases) clinic participated in the study. Fifty‐two percent had been homeless in the past 5 years and 84% are unemployed. Seventy‐two percent of patients did not complete second level education and 10% were illiterate. Fifty‐one percent had siblings or parents with a history of injection drug misuse, and 25% had at least one sibling also HIV positive. Forty‐seven percent started using drugs before the age of 13 years, and the most common initial drug was heroin (44%). Ninety‐five percent had attended for methadone maintenance therapy (MMT), with 39% currently attending for daily therapy. The majority of patients were unable to simply explain or interpret CD4 cell counts (54%) and ‘viral loads’ (65%). Fifty‐seven percent of patients were receiving highly active antiretroviral therapy (HAART). There was a statistically significant association between patients receiving HAART and both attendance at a primary care physician for methadone maintenance therapy (P = 0.005), and weekly take‐outs of methadone (P = 0.005). There was also an association between adherence to HAART and attendance at a methadone maintenance clinic (P = 0.04).

Conclusions

This study highlights the chaotic lifestyle and complex social background of the IDU. Such factors were not, however, associated with acceptance of HAART. The primary factor associated with both the acceptance of and adherence to HAART was regular and stable attendance for methadone therapy.