Suchergebnisse

Incidence of anal cancer is increasing and risk of anal cancer is higher in MSM, especially if they are HIV+. European guidelines for treatment of HIV‐infected adults recommend anal cancer screening by digital rectal exam±Pap test with anuscopy if Pap test is abnormal. A systematic anal cancer screening in HIV+MSM with anal cytology (Pap smears) was established in June 2011 in our reference centre in Brussels. If anal cytology was abnormal, high‐resolution anuscopy (HRA) with biopsy was performed. 353 MSM HIV+were screened by anal smears between June 2011 and May 2012. 90% were Caucasians, median age was 44.5 years, 83% were on HAART and 74% had an undetectable viral load, median CD4 was 632/µl and 33% had a nadir CD4<200. Thirty‐three (9.3%) were excluded because of poor quality. Cytology was abnormal in 46% of the 320 remaining patients: high‐grade squamous intraepithelial lesion (HSIL) 3%, low‐grade squamous intraepithelial lesion (LSIL) 24%, atypical squamous cells of undetermined significance (ASC‐US) 16%, and atypical squamous cells / cannot rule out a high‐grade lesion (ASC‐H) 3%. Viral load (VL) was more frequently undetectable (82% vs 64%, p=0.0003) and median duration of HAART was longer (111 vs 61 months, p=0.0145) in patients with normal cytology. 80 HRA with biopsies have been performed. 12.5% were normal, 44% showed anal intraepithelial neoplasia (AIN) 1, 24% AIN 2 and 19% AIN 3. For this analysis, high‐grade AIN (2 and 3) were put together (AIN 2+). Among patients with AIN 2+(n=33), cytology had showed 8 (24%) ASC‐US, 3 (9%) ASC‐H, 19 (57%) LSIL, 3 (9%) HSIL. When patients with normal cytology or normal biopsy and patients with AIN 2+were compared, the only significant risk factor found for AIN 2+was a nadir CD4<100/µl (32% of the patients with AIN 2+vs 14% in patients with normal smear, p=0.0073). Anal precancerous lesions are frequent and at different stages. Among 46% abnormal cytology, 87% had abnormal biopsy including half AIN 2+.Cytology±biopsy is the only way to detect those lesions and should be performed systematically in HIV+MSM. Risk factor for AIN2+was a nadir CD4<100/µl. A normal cytology was associated with an undetectable VL and a longer duration of HAART. Those results provide further argument for early initiation of HAART.

BackgroundIn the ECHO and THRIVE Phase III, randomised, double‐blind trials, rilpivirine (RPV, TMC278, EDURANT) 25 mg qd showed non‐inferiority compared to efavirenz (EFV) 600 mg qd in antiretroviral (ARV) treatment‐naïve, HIV‐1‐infected adults at Weeks 48 and 96. In Europe, RPV combined with other ARVs is approved for the treatment of ARV‐naïve adults with a viral load (VL) ≤100,000 c/mL. We present results from a pooled analysis of Week 96 data from this patient subgroup.MethodsPatients received RPV 25 mg qd or EFV 600 mg qd, both with TDF/FTC (ECHO) or TDF/FTC, AZT/3TC or ABC/3TC (THRIVE). Response rate (% VL <50 c/mL, intent‐to‐treat‐time‐to‐loss‐of‐virologic response [ITT‐TLOVR]), virologic failure in the resistance analysis (VFres) and resistance development, as well as safety and tolerability were evaluated.ResultsBaseline characteristics were similar between the 368 RPV and 329 EFV patients with baseline VL ≤100,000 c/mL. At Week 96, response rates (RPV 84% vs EFV 80%; difference 4.0% [95% CI: −1.7%, 9.7%]) and VFres percentages (8% vs 6%, respectively; p=0.46) (Table) were similar in each treatment group. A comparable proportion of VFres developed NNRTI resistance‐associated mutations (RAMs) in each group. More RPV than EFV VFres developed N(t)RTI RAMs (p=0.02). The increase in mean (95% CI) CD4+ cell count from baseline to Week 96 was 224 (208; 240) cells/mm3 for RPV and 206 (188; 225) cells/mm3 for EFV. Treatment‐related grade 2–4 overall AEs, any rash, and neurologic AEs, including dizziness were less frequent for RPV than EFV (all p<0.0001, Fisher's Exact test) (Table).













RPV N=368
EFV N=329



All
Up to Week 48
Weeks 48–96
All
Up to Week 48
Weeks 48–96




Resistance at time of failure


VFres, n (%)
28 (7.6)
20 (5.4)
7 (1.9)
20 (6.1)
14 (4.3)
6 (1.8)


VFres with genotypic data
N'=27
N'=19
N'=7
N'=17
N'=11
N'=6


developing NNRTI RAMs, n
10
7
2
6
5
1


developing N(t)RTI RAMs, n
12
8
3
2
2
0


Safety


AEs leading to discontinuation, n (%)
18 (4.9)
13 (3.5)
3 (0.8)
22 (6.7)
18 (5.5)
2 (0.6)


Grade 2–4 AEs at least possibility related to treatment,  n (%)
66 (17.9)
56 (15.2)
5 (1.4)
104 (32)
97 (29.5)
12 (3.6)


AEs of interest at least possibly related to treatment, n (%)


Any neurological AE
70 (19.0)
67 (18.2)
1 (0.3)
135 (41.0)
132 (40.1)
2 (0.6)


Dizziness
35 (9.5)
35 (9.5)
0
97 (29.5)
97 (29.5)
1 (0.3)


Any psychiatric AE
61 (16.6)
54 (14.7)
2 (0.5)
75 (22.8)
68 (20.7)
5 (1.5)


Abnormal dreams/nightmares
27 (7.3)
25 (6.8)
0
38 (11.6)
36 (10.9)
1 (0.3)


Rash (grouped term)
9 (2.4)
8 (2.2)
1 (0.3)
43 (13.1)
43 (13.1)
0




ConclusionsAt Week 96, in ARV treatment‐naïve adults with baseline VL ≤100,000 c/mL, RPV demonstrated sustained antiviral efficacy similar to EFV. There were similar frequencies of RPV and EFV VFres, and RPV had a more favourable safety/tolerability profile than EFV.

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

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

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