Initiation of an anal cancer screening in HIV+MSM: results of cytology, biopsy and determination of risk factors

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

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Early initiation of antiretroviral therapy and associated reduction in mortality, morbidity and defaulting in a nurse-managed, community cohort in Lesotho.

INTRODUCTION: The latest WHO guidelines recommend initiating antiretroviral therapy (ART) at CD4 cell counts less than 350 cells/μl. However, donors and national governments are reluctant to support implementation owing to uncertainty regarding feasibility and relative benefit. Lesotho has supported earlier initiation since 2008. We assessed outcomes comparing early (CD4 cell counts >200 cells/μl) and late (CD4 cell counts ≤200 cells/μl) initiation. METHODS: We describe survival probability among patients initiating ART at CD4 cell counts 200 or less and more than 200 cells/μl and assess associations between baseline CD4 cell counts and mortality, morbidity, loss to follow-up and hospitalization using Cox regression adjusting for confounders identified a priori. RESULTS: Our analysis included 1177 patients; median age was 38 years and the majority (67%) were women. Median time on ART for the overall cohort was 506 days (interquartile range 396-608). Five hundred and thirty eight patients initiated ART at a CD4 cell count 200 cells/μl or less (interquartile range 54-160) and 639 patients initiated at CD4 cell count more than 200 cells/μl (interquartile range 238-321). In multivariate analysis, we found that patients initiating at CD4 cell count more than 200 cells/μl were 68% less likely to die (adjusted hazard ratio 0.32, 95% confidence interval 0.20-0.50), and 39% less likely to be lost to follow-up (adjusted hazard ratio 0.61, 95% confidence interval 0.43-0.87). Initiating ART at CD4 cell count more than 200 cells/μl was also associated with a 27% reduction in the rate of incident morbidity (adjusted hazard ratio 0.73, 95% confidence interval 0.65-0.82) and a 63% decreased rate of hospitalization (adjusted hazard ratio 0.37, 95% confidence interval 0.19-0.73). CONCLUSION: Earlier initiation is feasible in a low resource, high HIV prevalence setting, and provides important benefits in terms of reduced mortality, morbidity, retention and hospitalization. Donors should fully support the implementation of the latest WHO recommendations

Neutralizing anti-Tat antibodies prolonged HAART interruption in vaccines in a prospective structured interruption study

Anti-Tat therapeutic vaccination has been clinically investigated by different groups [1-4], given that 1) extracellular Tat protein induces T cell apoptosis and cellular immune suppression, 2) epidemiological data showed that LTNP exhibit high level of serum anti-Tat Ab, negatively correlated with p24 antigenemia, 3) in Tat immunized macaques, viremia decreased following SHIV challenge. Anti-Tat therapeutic vaccination using Tat Toxoid adjuvanted either with Seppic [1,2] or with alum or DcChol (Aventis Pasteur) proved to be safe. A prospective structured treatment interruption study (STI) monitored according to EU guidelines was conducted at Hospital St-Pierre, Brussels (Pr. N. Clumeck) on 31 vaccinees who received a DcChol adjuvanted Tat Toxoid (n = 12), a DcChol placebo (n = 8) or non adjuvanted Tat toxoid (n = 11). The 2 year study follow-up showed that vaccinees developing high titer of Abs neutralizing Tat bioactivity prolonged HAART-interruption.info:eu-repo/semantics/publishedOral presentation. From 2006 International Meeting of The Institute of Human VirologyBaltimore, USA. 17–21 November, 200

Comparison of metabolic abnormalities and clinical lipodystrophy 48 weeks after switching from HAART to Trizivir versus continued HAART: the Trizal study

PURPOSE: To analyze the evolution of clinical lipodystrophy (LD) and metabolic abnormalities in patients continuing to receive HAART versus patients switched to Trizivir (zidovudine, lamivudine, abacavir) after 48 weeks. METHOD: Patients treated with HAART >6 months with plasma HIV-1 RNA viral load (VL) <400 copies/mL and <50 copies/mL at screening were randomly assigned to continue HAART (103 patients) or to receive Trizivir (106 patients). Clinical LD was evaluated using a standardized patient questionnaire only at baseline, weeks 4 and 8, and then every 8 weeks until Week 48. Laboratory evaluation was performed every 4 weeks. RESULTS: The proportion of patients exhibiting >or=1 LD symptom at baseline was 40% in the Trizivir arm and 50% in HAART arm (difference not significant). After 48 weeks, the prevalence was 28% and 42% respectively (p =.03), and the median number of LD symptoms per patient was 2 in the Trizivir arm and 4 in the continued HAART arm (p =.016). Median decreases in cholesterol levels over the 48-week study period were greater in the Trizivir arm than in the continued HAART arm (-0.80 vs. -0.44 mmol/L; p lt.001). Median triglyceride levels decreased in the Trizivir arm but increased in the continued HAART arm (-0.17 and +0.01 mmol/L; p =.006). Suppression of VL was maintained in most patients with no differences between the two arms. CONCLUSION: A switch from "standard" HAART to Trizivir was associated with an improvement in clinical LD and blood lipid abnormalities after 48 weeks

Limited HIV-1 Reactivation in Resting CD4+ T cells from Aviremic Patients under Protease Inhibitors.

peer reviewedA latent viral reservoir that resides in resting CD4+ T cells represents a major barrier for eradication of HIV infection. We test here the impact of HIV protease inhibitor (PI) based combination anti-retroviral therapy (cART) over nonnucleoside reverse transcriptase inhibitor (NNRTI)-based cART on HIV-1 reactivation and integration in resting CD4+ T cells. This is a prospective cohort study of patients with chronic HIV-1 infection treated with conventional cART with an undetectable viremia. We performed a seven-year study of 47 patients with chronic HIV-infection treated with cART regimens and with undetectable plasma HIV-1 RNA levels for at least 1 year. Of these 47 patients treated with cART, 24 were treated with a PI-based regimen and 23 with a NNRTI-based regimen as their most recent treatment for more than one year. We evaluated the HIV-1 reservoir using reactivation assay and integrated HIV-1 DNA, respectively, in resting CD4+ T cells. Resting CD4+ T cells isolated from PI-treated patients compared to NNRTI-treated patients showed a limited HIV-1 reactivation upon T-cell stimulation (p = 0.024) and a lower level of HIV-1 integration (p = 0.024). Our study indicates that PI-based cART could be more efficient than NNRTI-based cART for limiting HIV-1 reactivation in aviremic chronically infected patients