Suchergebnisse

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

From rented housing to meals on wheels; Great Britain.

The contribution that voluntary organizations can make to social welfare is affected by the fact that the branches of most national organizations are not distributed evenly over the country. The study reported here was carried out for the Wolfenden Committee on Voluntary Organizations in order to examine the extent of this unevenness and to see whether the distribution was random or followed a pattern.
The study was confined to the towns in England and Wales with a population in 1971 of over 50,000. London and the London boroughs were omitted. For each town the following information was obtained: 1) whether each of 22 national voluntary organizations had a branch located in the town; and 2) 26 indicators of economic and social conditions mostly drawn from the 1971 census. The 22 voluntary organizations and the 26 indicators are listed in Appendix 1.
The towns were classified on the basis of the 26 indicators, employing a technique derived from Moser and Scott's British Towns. A computer analysis was used to identify the main underlying factors that seemed to account for most variations in the 26 indicators.

Persistent immunosuppression despite viral suppression (immunovirological discordance, ID) has been associated with higher risk of AIDS and death, although the risk for AIDS seems to decrease with longer time of suppressed viral load (sVL). The impact of ID on a composite endpoint of AIDS/serious non‐AIDS/death has not been thoroughly investigated. Patients in EuroSIDA starting ≥1 new antiretroviral drugs after January 2001, when CD4 was <200 cells/mm3 and VL >500 copies/mL, and who achieved a sVL ≤50 copies/mL within 1 year were included. Person‐years of follow‐up (PYFU) accrued from the date of sVL until the first of a new AIDS or severe non‐AIDS (SNA) event or death, viral rebound >50 copies/mL (first of 2 consecutive values) or last visit. Rate ratios (RR) were calculated using Poisson regression according to whether or not patient's current CD4 count was still below 200 cells/mm3 (ID). Models were stratified according to whether or not persons were ART‐naïve at baseline. Multivariable models included age, HBV/HCV status, mode of HIV transmission, race, cohort, anemia, diabetes, hypertension or current eGFR, current cART, number of previous antiretrovirals, and time to viral suppression. 994 patients satisfied the inclusion criteria and contributed 4520 PYFU. Median age was 41 (IQR 34–47) years and 72.8% were male. 36.5% of patients were ART‐naïve and started a median of 3 (IQR 2–3) new drugs. 31 AIDS and 58 non‐AIDS events occurred, and 31 patients died (7 due to AIDS, 24 due to SNA). The rate of the combined endpoint in patients with ID (50.3 per 1000 PYFU [95% CI 35.2–69.9]) was higher than in patients recovered from ID (22.1 [17.6–27.3], adjusted RR 2.08 [1.32–3.28]; table). This was similar regardless of whether or not people were ART‐naïve before starting a new drug (interaction test p=0.47). In ID, rate was highest in the first 6 months of sVL (63.1 [33.6–107.9]) and declined thereafter (month 6–12: 60.5 [26.1–119.2],>12 months: 39.8 [22.2–65.6], adjusted RR compared to month 0–6 0.52 [0.24–1.13]). In analyses with endpoints AIDS/death due to AIDS and SNA/death due to SNA separately, the adjusted RR of ID vs. non ID was 4.11 ([1.76–9.60]; p=0.001) and 1.46 ([0.81–2.61]; p=0.207), respectively.











Exposure
No.events
PYFU
Rate (95%CI)
Crude RR (95%CI)
Adjusted**RR (95%CI)




All patients


No Discordance
84
3805
22.1 (17.6–27.3)
1
1


Discordance
36
716
50.3 (35.2–69.6)
2.28 (1.54–3.38)
2.08 (1.32–3.28)


ART‐naïve* patients


No Discordance
29
1324
21.9 (14.7–31.5)
1
1


Discordance
9
228
39.5 (18.1–74.9)
1.80 (0.84–3.85)
1.87 (0.81–4.33)


ART‐treated* patients


No Discordance
55
2481
22.2 (16.7–28.9)
1
1


Discordance
27
488
55.4 (36.5–80.6)
2.50 (1.67–3.97)
1.89 (1.08–3.32)





before starting a new antiretroviral drug according to the inclusion criteria, p(test for interaction):0.47
adjusted for smoking, HBV/HCV coinfection, transmission risk, race, cohort, current cART, change of ART before viral suppression, time to viral suppression, presence of diabetes, hypertension, anemia, current eGFR <90, CD4 nadir, CD4 count and viral load at baseline.

ID is a risk factor for clinical disease progression particularly related to AIDS events. In patients with ID, we found a trend for a declining incidence of events with longer periods of sVL, suggesting that sustained viral suppression might be of benefit.

BackgroundCD4 and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or negatively affect the risk of disease this would not be identified prior to licensing. The aims of this study were to investigate the CD4 and viral load specific rates of fatal and non‐fatal AIDS and non‐AIDS events according to current antiretrovirals.MethodsPoisson regression was used to compare overall events (fatal or non‐fatal AIDS, non‐AIDS or death), AIDS events (fatal and non‐fatal) or non‐AIDS events (fatal or non‐fatal) for specific nucleoside pairs and third drugs used with>1000 person‐years of follow‐up (PYFU) after January 1st 2001.Results9801 patients were included. The median baseline date was January 2004 (interquartile range [IQR] January 2001–February 2007), age was 40.4 (IQR 34.6–47.3 years), and time since starting cART was 3.3 (IQR 0.9–5.1 years). At baseline, the median nadir CD4 was 162 (IQR 71–257/mm3), baseline CD4 was 390 (IQR 249–571/mm3), viral load was 1.9 (IQR 1.7–3.3 log10copies/ml) and 2961 (30.2%) had a prior AIDS diagnosis and 6.4 years) prior to baseline. During 42372.5 PYFU, 1203 (437 AIDS and 766 non‐AIDS) events occurred. The overall event rate was 2.8 per 100 PYFU (95% confidence interval [CI] 2.7–3.0), of AIDS events was 1.0 (95% CI 0.9–1.1) and of non‐AIDS events was 1.8 (95% CI 1.7–1.9). Of the AIDS events, 53 (12.1%)were fatal as were 239 (31.2%) of the non‐AIDS events. After adjustment, there was weak evidence of a difference in the overall events rates between nucleoside pairs (global p‐value=0.084), and third drugs (global p‐value=0.031). Compared to zidovudine/lamivudine, patients taking abacavir/lamivudine (adjusted incidence rate ratio [aIRR] 1.22; 95% CI 0.99–1.49) and abacavir plus one other nucleoside (aIRR 1.51; 95% CI 1.14–2.02) had an increased incidence of overall events. Comparing the third drugs, those taking unboosted atazanavir had an increased incidence of overall events compared to those taking efavirenz (aIRR 1.46; 95% CI 1.09–1.95)(Figure).imageConclusionsThere was little evidence of substantial differences between antiretrovirals in the incidence of fatal and non‐fatal AIDS and non‐AIDS events for a given CD4 or viral load, suggesting there are unlikely to be major unidentified adverse effects of specific antiretrovirals, although confounding by indication cannot be ruled out.

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

BackgroundIn the last decade, several outbreaks of sexually acquired acute HCV have been described in men who have sex with men (MSM) infected with HIV in Australia, Europe, and North America. The aims of this study were to determine the incidence of acute HCV within the large EuroSIDA cohort and to explore possible regional differences throughout Europe and in different HIV transmission risk groups.MethodsBaseline was defined as 1st Jan of 2002 or entry into EuroSIDA, whichever comes later. All patients from EuroSIDA who were HCV antibody‐negative at baseline and had at least 2 HCV antibody test results available were included into the study. HCV seroconversion was defined as change from negative to positive HCV‐antibody test within the observation period from 2002 onwards. Follow‐up was counted from baseline to HCV antibody positivity for seroconverters and to the last HCV antibody‐negative test result for those that did not seroconvert for HCV. Poisson regression analyses were performed to identify predictive factors for HCV seroconversion.ResultsA total of 150 HCV seroconversions (95 [63.3%] in MSM) occurred in 4295 patients during 18,928 person years of follow‐up (PYFU), overall incidence of 0.79 acute infections per 100 PYFU (95% CI: 0.67–0.92) (see figure). The incidence of HCV seroconversions increased from 0.47 (CI: 0.19–0.74) in 2002 to 2.34 (CI: 1.24–3.44) in 2010. Similar patterns were observed across all European regions (p=0.89, test for interaction). In multivariate analysis, IDU was associated with a higher incidence rate ratio (IRR) than MSM: 4.59 (2.40–8.80; p<0.0001), South and East Europe both had higher IRR compared to Western Europe, respectively (1.98 [1.12–3.49]; p=0.018 and 2.41 [1.41–4.12]; p=0.0014). Calendar year per 2 years was also associated with a higher IRR (1.29 [1.19–1.39]; p<0.0001).ConclusionThe incidence of acute HCV within EuroSIDA increased over time. Although, the incidence of seroconversion was 54% higher in MSM than in heterosexuals, IDUs had the highest incidence of HCV seroconversion. Rising incidences can be found in all European regions highlighting the need for increased prevention efforts in all European countries.
image

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

Purpose of the studyTo investigate the impact of ART, HIV viremia and immunosuppression on triglyceride (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL‐C) levels.MethodsWe considered the cross‐sectional associations between TG, TC and HDL‐C (mmol/l; first available measurement on/after enrolment in the D:A:D study) and use of ART, HIV viral load (VL; copies/ml), and CD4 count (cells/mm3) measured at the same time. TG was log10 transformed to ensure normality. Analyses were performed using linear regression and adjusted for other factors known to impact lipid levels (table footnote). ART and VL status were combined (off ART&VL >100,000, off ART&VL <100,000, on ART&VL <500, on ART&VL >500), current and nadir CD4 count were categorised as <200, 200–349, 350–499 and >500.Summary of results44,322/49,734 participants in the D:A:D Study (89.1%) contributed a TG measurement (median; IQR 1.52; 1.00–2.45), 45,169 (90.8%) a TC measurement (4.80; 4.00–5.70) and 38,604 (77.6%) a HDL‐C measurement (1.12; 0.90–1.40). Most participants were male (74%), of white ethnicity (51%), without AIDS (78%), were not receiving lipid‐lowering drugs (4%) and were ART experienced (61%) with 47% previously exposed to PIs, 61% previously exposed to NRTIs and 29% previously exposed to NNRTIs. The median (IQR) age, current CD4 count and CD4 nadir were 38 (36–45) years, 400 (242–590) cells/µl and 240 (100–410) cells/µl respectively. Compared to those on ART with a suppressed VL, all lipids were lower for those off ART (Table); non‐suppressive ART was also associated with lower TC and HDL‐C levels (no impact on TG). A low current CD4 count was associated with lower lipid levels, whereas a low nadir CD4 count was associated with higher TC and TG levels. Prior AIDS diagnosis was associated with higher TG and TC, but lower HDL‐C levels.

Impact of ART, immunosuppression and viraemia, on TG, TC and HDL‐C (mmol/l)












Average impact on log10TG*†

Average inpact on TC*
Average impact on HDL‐C*




ART and VL


Off ART … VL≥100000
−0.09 (−0.10,−0.08)
<0.001
−0.55 (−0.60,−0.51)
<0.001
−0.14 (−0.16,−0.13)
<0.001


Off ART … VL<100000
−0.04 (−0.06,−0.03)
<0.001
−0.85 (−0.91,−0.78)
<0.001
−0.31 (−0.33,−0.29)
<0.001


On ART … VL<500
Ref

Ref

Ref



On ART … VL≥500
0.00 (−0.01, 0.00)
0.38
−0.40 (−0.44,−0.36)
<0.001
−0.16 (−0.17,−0.15)
<0.001


CD4 count


<200
−0.03 (−0.04,−0.02)
<0.001
−0.33 (−0.39,−0.28)
<0.001
−0.04 (−0.06,−0.02)
<0.001


200–349
−0.02 (−0.03,−0.01)
<0.001
−0.11 (−0.15,−0.06)
<0.001
0.00 (−0.01, 0.02)
0.72


350–499
Ref

Ref

Ref



500+
0.04 (0.03, 0.04)
<0.001
0.12 (0.08, 0.16)
<0.001
−0.02 (−0.03,−0.00)
0.02


Nadir CD4 Count


<200
0.07 (0.06, 0.08)
<0.001
0.19 (0.14, 0.24)
<0.001
−0.05 (−0.06,−0.03)
<0.001


200–349
0.02 (0.01, 0.03)
<0.001
0.01 (−0.03, 0.06)
0.57
−0.03 (−0.05,−0.02)
<0.001


350–499
Ref

Ref

Ref



500 +
0.00 (−0.02, 0.01)
0.33
0.03 (−0.02, 0.09)
0.23
0.04 (0.02, 0.06)
<0.001


Prior AIDS
0.05 (0.05, 0.06)
<0.001
0.11 (0.08, 0.15)
<0.001
−0.03 (−0.04,−0.01)
<0.001





estimates included are mutually adjusted for each other and for the following demographic variables: age; gender; mode of infection; ethnicity; body mass index; smoking; family history of CVD; diabetes; use of lipid lowering drugs; co‐infection with hepatitis C; participating cohort; and year of entry into study.
TG is log10 transformed. Thus, the results presented for TG reflect relative rather than absolute effects. For example, lipid levels for those off ART … VL ≥100000 are 9% lower than those on ART … VL < 500.

ConclusionAlthough specific drug classes were not considered, lipid levels are considerably higher in those on a suppressive ART regimen. The higher TC/TG and lower HDL‐C levels seen among those with low nadir CD4 count and with a prior AIDS diagnosis suggests severe immunosuppression may be associated with dyslipidaemia over the long‐term.

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK