Marc Delforge

Characteristics of non-AIDS-defining malignancies in the HAART era: a clinico-epidemiological study

BackgroundNon-AIDS-defining malignancies (NADM) are becoming a major cause of mortality in the era of highly active antiretroviral therapy. We wished to investigate the incidence, risks factors and outcome of NADM in an urban cohort.MethodsWe carried out an observational cohort of HIV patients with 12,746 patient-years of follow up between January 2002 and March 2009. Socio-demographics and clinical characteristics of patients diagnosed with NADM were retrospectively compared with the rest of the cohort. Causes of death and risk factors associated with NADM were assessed using logistic regression. Survival analyses were performed with Kaplan-Meier estimates. Cancer incidences were compared with those of the general population of the Brussels-Capital Region using the standardized incidence ratio (SIR).ResultsForty-five NADM were diagnosed. At inclusion in the study, patients with NADM were older than patients without NADM (47 years vs. 38 years, p < 0.001), had a longer history of HIV infection (59 months vs. 39 months, p = 0.0174), a lower nadir CD4 count (110 cells/mm3 vs. 224 cells/mm3, p < 0.0001) and a higher rate of previous AIDS events (33% vs. 20%, p = 0.0455) and of hepatitis C virus co-infection (22.2% vs. 10%, p = 0.0149). In multivariate analysis, age over 45 at baseline (OR 3.25; 95% CI 1.70-6.22) and a nadir CD4 count of less than 200 cells/mm3 (OR 3.10; 95% CI 1.40-6.87) were associated with NADM. NADM were independently associated with higher mortality in the cohort (OR 14.79; 95% CI 6.95-31.49). Women with cancer, the majority of whom were of sub-Saharan African origin, had poorer survival compared with men. The SIR for both sexes were higher than expected for Hodgkins lymphoma (17.78; 95% CI 6.49-38.71), liver cancers (8.73; 95% CI 2.35-22.34), anal cancers (22.67; 95% CI 8.28-49.34) and bladder cancers (3.79; 95% CI 1.02-9.70). The SIR for breast cancer was lower in women (SIR 0.29; 95% CI 0.06-0.85).ConclusionsAge over 45 and a nadir CD4 count of less than 200 cells/mm3 were predictive of NADM in our cohort. Mortality was high, especially in sub-Saharan African women. Cancers with increased incidences were Hodgkins lymphoma and anal, bladder and liver cancers in both sexes; women had a lower incidence of breast cancer.

Sustained Viral Suppression and Higher CD4+ T-Cell Count Reduces the Risk of Persistent Cervical High-Risk Human Papillomavirus Infection in HIV-Positive Women

BACKGROUND Studies analyzing the impact of combination antiretroviral therapy (cART) on cervical infection with high-risk human papillomavirus (HR-HPV) have generated conflicting results. We assessed the long-term impact of cART on persistent cervical HR-HPV infection in a very large cohort of 652 women who underwent follow-up of HIV infection for a median duration of 104 months. METHODS Prospective cohort of HIV-infected women undergoing HIV infection follow-up who had HR-HPV screening and cytology by Papanicolaou smear performed yearly between 2002 and 2011. RESULTS At baseline, the median age was 38 years, the race/ethnic origin was sub-Sarahan Africa for 84%, the median CD4(+) T-cell count was 426 cells/µL, 79% were receiving cART, and the HR-HPV prevalence was 43%. The median interval of having had an HIV load of <50 copies/mL was 40.6 months at the time of a HR-HPV-negative test result, compared with 17 months at the time of a HR-HPV-positive test result (P < .0001, by univariate analysis). The median interval of having had a CD4(+) T-cell count of >500 cells/µL was 18.4 months at the time of a HR-HPV-negative test result, compared with 4.45 months at the time of a HR-HPV-positive test result (P < .0001). In multivariate analysis, having had an HIV load of <50 copies/mL for >40 months (odds ratio [OR], 0.81; 95% confidence interval [CI], .76-.86; P < .0001) and having had a CD4(+) T-cell count of >500 cells/µL for >18 months (OR, 0.88; 95% CI, .82-.94; P = .0002) were associated with a significantly decreased risk of HR-HPV infection. CONCLUSION Sustained HIV suppression for >40 months and a sustained CD4(+) T-cell count of >500 cells/µL for >18 months are independently and significantly associated with a decreased risk of persistent cervical HR-HPV infection.

Downregulation of CD38 activation markers by atorvastatin in HIV patients with undetectable viral load.

Immune activation and chronic inflammation are recognized as major component of HIV disease even in patients with undetectable viral load. We evaluated the effect of atorvastatin on CD38 activation in such patients, in a case–control study (133 cases – 266 controls). At week 48, CD38 activation was significantly lower in cases vs. controls, with no difference in high-sensitivity C-reactive protein (hsCRP) and CD4. These results suggest that atorvastatin reduces the level of immune activation in patients with undetectable viral load.

High-risk human papillomavirus infection in HIV-positive African women living in Europe

Cervical infection with high‐risk human papillomavirus (HRHPV) induces cervical cancer and is present in 14% of women in Europe. We assessed the prevalence and incidence of cervical HRHPV in a cohort of HIV‐positive women living in Belgium.

First-line antiretroviral therapy with nevirapine versus lopinavir-ritonavir based regimens in a resource-limited setting.

Objective:To compare WHO first-line antiretroviral therapy (ART) with nonnucleoside reverse transcriptase inhibitors (NNRTI)-based regimen with a boosted protease inhibitor (bPI) regimen in a resource-limited setting regarding treatment outcome and emergence of drug resistance mutations (DRMs). Methods:Treatment-naive adults were randomized to nevirapine (NVP) or ritonavir-boosted lopinavir (LPV/r) regimens each in combination with tenofovir (TDF)/emtricitabine (FTC) or zidovudine (ZDV)/lamivudine (3TC). Primary endpoint was the incidence of therapeutical (clinical and/or virologic) failure at week 48 with follow-up till week 96. Results:Four hundred and twenty-five patients (120 men; 305 women) received at least one dose of the study drug. mITT analysis showed no difference in proportion of therapeutical failure between treatment arms [67/209 (32%) in NVP vs. 63/216 (29%) LPV/r at week 48 (P = 0.53); 88/209 (42%) in NVP vs. 83/216 (38%) in LPV/r at week 96 (P = 0.49)]. Per-protocol analysis demonstrated significantly more virologic failure with NVP than with LPV/r regimens [at week 48: 19/167 (11%) vs. 7/166 (4%), P = 0.014; at week 96: 27/158 (17%) vs. 13/159 (8%), P =  0.019)]. Drug resistance mutations to NNRTI were detected in 19 out of 22 (86.3%) and dual-class resistance to nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI in 15 out of 27 (68.2%) of NVP failing patients. K65R mutation was present in seven out of 14 patients failing NVP-TDF/FTC regimen. No major protease inhibitor-DRM was detected among LPV/r failing patients. Discontinuation for adverse events was similar between treatment groups. Conclusion:In resource-limited settings, first-line NNRTI-NRTI regimen as compared with bPI-based regimen provides similar outcome but is associated with a significantly higher number of virologic failure and resistance mutations in both classes that jeopardize future options for second-line therapy.

Cardiovascular risk evaluation of HIV-positive patients in a case-control study: comparison of the D:A:D and Framingham equations.

Patients with HIV infection are at increased risk of developing cardiovascular disease (CVD) due to complex interactions between traditional CVD risk factors, antiretroviral therapy (ART) and HIV infection itself [ 1 ]. Prevention of CVD is essential as it remains the most common serious non‐AIDS event and contributes significantly to all‐cause mortality. A cardiovascular risk‐assessment model tailored to HIV population is thus essential.

Prolonged antiretroviral therapy is associated with fewer anal high-grade squamous intraepithelial lesions in HIV-positive MSM in a cross-sectional study

Objective HIV-positive men who have sex with men (MSM) are at increased risk of anal cancer. We evaluate the risk factors for anal high-grade squamous intraepithelial lesion (HSIL) (the precursor of anal cancer) in HIV-positive MSM. Methods In this cross-sectional study within a cohort, 320 HIV-positive MSM were screened by anal cytology followed by high-resolution anoscopy (HRA) in case of abnormal cytology. Risk factors for anal HSIL were analysed. Results Men were mostly middle-aged Caucasians with median CD4+ T lymphocytes of 638 cells/µL, 87% on combined antiretroviral therapy (cART) for a median of 5 years. 198 anal cytology samples were normal. In the 122 patients with abnormal cytology, HRA with biopsies were performed: 12% (n=15) normal, 36% (n=44) anal low-grade squamous intraepithelial lesion (LSIL) and 51% (n=63) anal HSIL. Comparing patients with or without anal HSIL (normal cytology or normal biopsy or LSIL), we found in multivariate analysis significantly fewer anal HSIL in patients with cART ≥24 months (OR 0.32 CI 95% 0.162 to 0.631, p=0.001). Conclusions Prolonged cART (≥24 months) is associated with fewer anal HSIL.

High-risk human papillomavirus genotypes distribution in a cohort of HIV-positive women living in Europe: epidemiological implication for vaccination against human papillomavirus.

Background:Worldwide, human papillomavirus (HPV) 16 and 18 represents 70% of high-risk (HR) HPV found in cervical cancer. However HIV-positive women are more frequently infected by HRHPV other than HPV 16 or 18 (OHR). We aimed to analyse the HRHPV genotype distribution in a cohort of HIV-positive women and to estimate the potential protection offered by the different HPV vaccines. Methods:HRHPV genotypes by PCR and cytology were assessed in cervical samples from 508 HIV-positive women prospectively followed in Brussels. Results:Women characteristics were as follows: African origin (84%), median age 42 years, median CD4+ T 555/&mgr;l, 89% under combined antiretroviral therapy and 73% with HIVRNA less than 20 copies/ml. HRHPV prevalence was 23% (116/508): 38% had abnormal cytology, 76% carried OHR without HPV 16 or 18 and 11% had concomitant infection by OHR and HPV 16 or 18. The most frequent HRHPV were HPV52 (19.8%), HPV18 (14.6%), HPV31/35/51/58 (12.1% each), HPV56 (9.9%) and HPV16 (9.5%). Less than 30% of women had their HRHPV genotypes included in the bivalent or quadrivalent vaccines against HRHPV 16 and 18; however, 79% had their HRHPV covered by the ninevalent vaccine against HRHPV 16/18/31/33/45/52/58. Conclusion:The HRHPV genotypes distribution found in these women living in Europe with a successfully treated HIV is similar to the one found in Central Africa with HRHPV other than HPV16 or 18 retrieved in 87%. In this population, the bivalent or quadrivalent vaccines could offer protection in only 30% of women; however this protection could be extended up to 80% with the ninevalent vaccine.

First-line therapy with LPV/r vs NVP and 2 NRTIs in a developing country: W144 of a randomized trial.

Materials and methods Naive p. from 5 clinics in Lubumbashi (Congo-DRC) were randomized to receive LPV/r versus NVP combined with TDF/FTC or ZDV/3TC. VL and CD4 were performed at baseline (BL) and every 24 weeks (W). The primary endpoint was the % of p. with therapeutic failure defined as clinical and virologic failures (VL>1000 c/ml)(missing data=failure), assessed at W48 and 96. We present here the results of 144 W of follow-up.

Treatment of anal dysplasia in HIV-positive men who have sex with men in a large AIDS reference centre

Objectives: Over the last few decades, incidence of anal cancer among HIV-positive men has been on the rise. In this context, programmes of screening and treatment of anal dysplasia which is a precursor of anal cancer have been developed. The aim of our study was to describe the efficiency, side effects and outcome of anal dysplasia treatment in a population of HIV-positive men who have sex with men (MSM). Methods: We performed a retrospective study of HIV-positive MSM who received treatment for anal dysplasia between May 2010 and February 2014 in the Saint-Pierre University Hospital, Brussels. The different treatments used were electrocautery (ECA), infrared coagulation (IRC), surgical treatment and imiquimod. Results: Seventy-three HIV-infected MSM were included in the study, counting 62% of HGAIN. Median age was 41 years. Eighty-one per cent were on HAART. Median CD4 cell count was 525 cell/mm³, and 65% had undetectable viral loads. A total of 139 therapeutic interventions were recorded during the study period, and two-thirds of the enrolled patients received more than one treatment. At 540 days of follow-up, the rate of treatment response was 62%. Fifty per cent of the persistent HGAIN were metachronous lesions. No severe adverse events were recorded but frequent treatment-associated discomfort was reported, such as pain, self-limited bleeding, infection and anal irritation. Conclusion: Treatment of anal dysplasia appears to be safe and to offer short-term efficiency. However, its long-term efficiency remains unknown, especially in the HIV-positive population in which spontaneous clearance is lower and rate of recurrence higher.