Suchergebnisse

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

Criteria of cART initiation after a first ADE have been modified over time based on evidence suggesting that treatment should be initiated earlier. The impact of these changes on clinical practice is unknown. Objective of this analysis was to evaluate temporal changes of time of starting cART after a first diagnosis of ADE in ART‐naïve patients (pts).MethodsAll HIV+ enrolled in ICONA Foundation Study who presented with a diagnosis of ADE while cART‐naïve regardless of CD4 cell count were included. Pts were grouped according to have ADE for which additional medications that may have interactions with cART are required (Tb, atypical mycobacteriosis, non‐Hodgkin lymphoma) [group A], ADE treatable only by cART (PML, isosporidiasis/cryptosporidiasis, KS, wasting syndrome) [group B] and ADE treatable with specific drugs (PCP, toxoplasmic encephalitis, CMV disease, esoph candidiasis, bacterial pneumonia, cervical cancer, cryptococcosis) [group C]. Standard survival analysis by KM was used to estimate the cumulative percentage of pts starting cART, overall and after stratification for calendar period of diagnosis (1996–2000, 2001–2008, 2009–2011) and type of ADE (groups A, B, C). Multivariable Cox regression was used to investigate association between calendar year of ADE and time to cART initiation after controlling for demographics.Summary of resultsA total of 715 pts with a first ADE were observed over 1996‐2011 (group A, n=187; B, n=123; C, n=405). 519 (73%) male, median age 38 (IQR:33–45), median CD4+64 (23–187)/mm3 and HIV/RNA 5.25 (4.57–5.70) log10 cps/mL, with no differences by calendar period. By 30 days from ADE, 23% (95% CI: 19–27) of those diagnosed in 1996–2000 have started cART vs. 32% (95% CI: 25–39) in 2001–2008 and 36% (28–44) after 2009 (log‐rank p=0.001). After stratifying by CD4 at ADE, 45% of pts with CD4<50/mm3, 30% of those with 51–200/mm3 and 16% of those>201/mm3 had started cART by 30 days (p<0.0001). Restricting the analysis to pts diagnosed after 2009, the percentages of cART initiation were 9% for group A, 52% for group B and 39% for group C (p=0.05). The table shows the relative hazards of starting cART from fitting a multivariable Cox regression model.ConclusionsIn our 'real‐life' setting, time from AIDS diagnosis to cART was significantly shorter in pts diagnosed in more recent years, although for most ADE cART initiation was less prompt than expected, even in pts with severe immunodeficiency.










Calendar Period
Crude RH (95% CI)
p‐value
Adjusted RH (95% CI)
p‐value




1996–1999
1.00

1.00



2000–2008
1.19 (0.95, 1.50)
0.132
1.18 (0.88, 1.57)
0.272


2009+
1.51 (1.16, 1.96)
0.002
1.36 (0.89, 2.08)
0.151


Type of ADE
Crude RH (95%)
p‐value
Adjusted RH (95% CI)
p‐value


A
1.00

1.00



B
2.59 (1.90, 3.53)
<.001
2.24 (1.44, 3.48)
<.001


C
2.09 (1.65, 2.67)
<.001
1.14 (0.99, 2.00)
0.058

PREVALEAT II (PREmature VAscular LEsions and Antiretroviral Therapy II) is an ongoing multicenter, longitudinal cohort study aimed to the evaluation of cardiovascular risk in advanced naïve HIV‐infected patients starting their first HAART. It includes all consecutive naïve pts with <200 CD4 cells/ml who start any PI/r‐based or NNRTI‐based+2 NRTIs regimen. Pts are subjected to epi‐aortic vessels ultrasonography, brachial artery flow mediated dilation (FMD), endothelial cytokine inflammatory markers value at time 0 and after 3, 6 and 12 months. Data about independent risk factors for CV disease are taken at time 0. Viral load, CD4+ counts, serum lipid values, glucose, body mass index (BMI) are recorded at every control. We enrolled 47 pts: 76,6% males, 87,2% caucasians, 40,4% cigarette smokers, 10,6% HCV co‐infected, 6,4% had lipodystrophy. 29,8% homosexuals, 12,8% drug addicts, 51,1% heterosexuals. At baseline, 23,4% of pts had pathologic BMI, 31,91% had a epi‐aortic vessels lesion (IMT and/or plaque), 27,65% had pathologic FMD; ICAM1 was pathologic in 46,80%, VCAM1 in 53,19%, IL‐6 in 51,06%, D‐dimers in 29,79%, hsCRP in 23,40%. 27 pts completed stage T1 of the study (after 3 months); percentages and significance level of variations are the following: 44,44% had a lesion of the epi‐aortic vessels (p=0,28), 48,14% had a pathologic FMD (p=0,08), ICAM1 was pathologic in 59,26% (p=0,30), VCAM1 in 70,37% (p=0,15), IL‐6 in 74,07% (p=0,05), D‐dimers in 14,81% (p=0,12), hsCRP in 25,92% (p=0,80). 27 pts completed stage T2 of the study (6 months). Percentages and significance level of variations in regard of baseline are the following: 51,85% had a epi‐aortic vessels lesion (p=0,462); 25,92% had pathologic FMD (p=0,37). 10 pts completed stage T3 of the study (12 months): 60% had a epi‐aortic vessels lesion (p=0,07); 40% had pathologic FMD (p=0,49). No significant change has been showed in the trend of variation of inflammatory cytokines at T2 and T3. Our data, at baseline, evidence that advanced naïve pts show a relevant deterioration of CV conditions in terms of US data, FMD and cytokine markers. At T1, US and FMD seem to further worsen; cytokines, except D‐dimers, show a worsening trend, too. At T1 and T2, prevalence of vessel lesion and pathologic FMD is yet higher, with a p value closer to significance level. Further data deriving from the follow‐up of missing pts are warranted to better understand the evolution of the CV risk profile in this setting of pts.

In HIV‐positive patients (pts), CMV co‐infection has been proposed as a key factor in sustaining immune activation, which in turn could play a role in determining immune senescence. We evaluated the prevalence and predictors of CMV co‐infection in a cohort of HIV+ pts and assessed the impact of CMV co‐infection on the risk of AIDS and non‐AIDS events. We included pts in the ICONA study with<1 month follow‐up and<1 CMVIgG (CMV) test available without active CMV disease. Pts' characteristics at time of the first CMV test (baseline) were compared in those tested positive (CMV+) and negative (CMV‐) using X2/Wilcoxon tests. Factors associated with CMV+ were identified by logistic regression. A prospective analysis was also performed with endpoints AIDS/AIDS‐related death and severe non‐AIDS (SNA: cardio‐cerebrovascular, neurologic disease, renal failure, non‐AIDS tumours)/death due to SNA. Time to event was estimated by Kaplan‐Meier curves and Cox regression (multivariable model included: age, gender, ethnicity, risk factor for HIV, HCVAb and HBsAg, AIDS and CD4 at baseline, initiation of ART prior to baseline). 6,053 pts were included; 83.7% were tested CMV+ a median of 17 (IQR 6–45) months after enrolment. As compared to CMV‐, CMV+ were older (adjusted odds ratio (AOR) 1.03 per 1 year older [95% CI 1.02–1.04]), HIV infected by homosexual route (MSM) (AOR 1.39 [95% CI 1.06–1.82]), less frequently Caucasian (AOR 0.56 [95% CI 0.42–0.76]), with higher CD4 count at baseline (AOR per 1 cell higher 1.035 [95% CI 1.00–1.06] By 10 years from first CMV test, 402 (12.6% [95% CI 11.1–13.6]) CMV+ and 74 (10.1% [95% CI 7.7–12.5]) CMV‐ pts developed AIDS/AIDS‐related death (log‐rank p=0.43). After adjustment for potential confounders, CMV+was still not associated with the risk of AIDS/AIDS‐related death (adjusted hazard ratio (AHR) 1.23 [95% CI 0.96–1.60]). By 10 years, 339 (10.6% [95% CI 9.4–11.9]) CMV+ and 41 (6.4% [95% CI 6.1–6.6]) CMV‐ pts experienced a non‐AIDS event/non‐AIDS death (log‐rank p=0.0006): 151 cancers, 128 CVD, 33 neurological, 1 renal. The association was still significant after controlling for a number of potential confounders: AHR 1.77 [95% CI 1.25–2.51] p=0.001; Table). In our study population, CMV/HIV co‐infection was associated with the risk of non‐AIDS events/deaths independently of other prognostic factors, supporting a potential role of CMV infection in vascular/ degenerative organ disorders commonly associated with chronic immune activation and aging.









Characteristic
AHR
95% CI
p‐value




CMVIgg+vs. CMVIgg−
1.77
1.25–2.51
0.001


Age, per 10 years older
1.64
1.46–1.84
0.0001


Female vs. male
1.43
1.12–1.83
0.004


Caucasian vs. Other
0.64
0.40–1.02
0.06


Homosexuals vs. IVDU
0.84
0.55–1.28
0.42


Heterosexuals vs. IVDU
0.87
0.60–1.26
0.47


HCVAb+vs. HCVAb−
1.28
0.92–1.78
0.13


HBsAg+vs HBsAg−
1.05
0.67–1.62
0.83


AIDS at baseline
0.94
0.67–1.32
0.75


CD4/µL at baseline per 100 cells/µL higher
0.97
0.93–1.01
0.16


HIV‐RNA at baseline per log10 cp/mL higher
1.05
0.96–1.16
0.26


Years from HIV diagnosis per 5 years longer
1.02
0.90–1.17
0.69


ART experienced vs. naïve at baseline
0.94
0.66–1.36
0.77

Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood. Here we analyze a large dataset of globally representative HIV-1 subtype B strains to map their spread around the world over the last 50 years and describe significant spread patterns. We show that subtype B travelled from North America to Western Europe in different occasions, while Central/Eastern Europe remained isolated for the most part of the early epidemic. Looking with more detail in European countries we see that the United Kingdom, France and Switzerland exchanged viral isolates with non-European countries than with European ones. The observed pattern is likely to mirror geopolitical landmarks in the post-World War II era, namely the rise and the fall of the Iron Curtain and the European colonialism. In conclusion, HIV-1 spread through specific migration routes which are consistent with geopolitical factors that affected human activities during the last 50 years, such as migration, tourism and trade. Our findings support the argument that epidemic control policies should be global and incorporate political and socioeconomic factors.

Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood. Here we analyze a large dataset of globally representative HIV-1 subtype B strains to map their spread around the world over the last 50 years and describe significant spread patterns. We show that subtype B travelled from North America to Western Europe in different occasions, while Central/Eastern Europe remained isolated for the most part of the early epidemic. Looking with more detail in European countries we see that the United Kingdom, France and Switzerland exchanged viral isolates with non-European countries than with European ones. The observed pattern is likely to mirror geopolitical landmarks in the post-World War II era, namely the rise and the fall of the Iron Curtain and the European colonialism. In conclusion, HIV-1 spread through specific migration routes which are consistent with geopolitical factors that affected human activities during the last 50 years, such as migration, tourism and trade. Our findings support the argument that epidemic control policies should be global and incorporate political and socioeconomic factors.