Incidence of cervical, breast and colorectal cancers between 2010 and 2015 in people living with HIV in France.

BACKGROUND: We aimed to evaluate the incidence rates between 2010 and 2015 for invasive cervical cancer (ICC), breast cancer (BC), and colorectal cancer (CRC) in people living with HIV (PLWH) in France, and to compare them with those in the French general population. These cancers are targeted by the national cancer-screening program. SETTING: This is a retrospective study based on the longitudinal data of the French Dat'AIDS cohort. METHODS: Standardized incidence ratios (SIR) for ICC and BC, and incidence rates for all three cancers were calculated overall and for specific sub-populations according to nadir CD4 cell count, HIV transmission category, HIV diagnosis period, and HCV coinfection. RESULTS: The 2010-2015 CRC incidence rate was 25.0 [95% confidence interval (CI): 18.6-33.4] per 100,000 person-years, in 44,642 PLWH (both men and women). Compared with the general population, the ICC incidence rate was significantly higher in HIV-infected women both overall (SIR = 1.93, 95% CI: 1.18-3.14) and in the following sub-populations: nadir CD4 ≤ 200 cells/mm3 (SIR = 2.62, 95% CI: 1.45-4.74), HIV transmission through intravenous drug use (SIR = 5.14, 95% CI: 1.93-13.70), HCV coinfection (SIR = 3.52, 95% CI: 1.47-8.47) and HIV diagnosis before 2000 (SIR = 2.06, 95% CI: 1.07-3.97). Conversely, the BC incidence rate was significantly lower in the study sample than in the general population (SIR = 0.56, 95% CI: 0.42-0.73). CONCLUSION: The present study showed no significant linear trend between 2010 and 2015 in the incidence rates of the three cancers explored in the PLWH study sample. Specific recommendations for ICC screening are still required for HIV-infected women and should focus on sub-populations at greatest risk.

Spectrum and Incidence Trends of AIDS- and Non-AIDS-Defining Cancers between 2010 and 2015 in the French Dat'AIDS Cohort.

BACKGROUND: Cancer risk is higher in people living with HIV (PLWH) compared with the general population, and cancers related to age are expected to be most prevalent. METHODS: We determined the spectrum and incidence rates of AIDS-defining cancers (ADC) and non-AIDS-defining cancers (NADC) and of lung, Hodgkin lymphoma (HL), head and neck (HNC), colon-rectum, anal, liver, breast, prostate, and urinary bladder cancers between January 2010 and December 2015 in the French Dat'AIDS cohort. Incidence rates were calculated by year and compared using the χ 2 test for linear trend. Standardized incidence ratios [SIR (95% confidence interval)] were calculated relative to the French general population. RESULTS: Among 44,642 patients, corresponding to 180,216.4 person-years (PY), 1,440 cancer cases occurred in 1,314 patients. ADC incidence was 191.4 (172.3-212.7)/105 PY and declined over time overall and in men, whereas NADC incidence was higher [548.8 (515.6-584.1)/105 PY] and did not change. In men, non-Hodgkin lymphoma was the most common cancer, but prostate cancer had the highest incidence among NADCs. Breast cancer was the most common cancer in women. SIRs were higher for cervical cancer [1.93 (1.18-3.14)], HNC in women [2.4 (1.4-4.2)], liver [overall: 3.8 (3.1-4.6); men: 3.2 (2.5-4.0); women: 12.9 (8.3-20.0)], and HL [overall: 13.8 (11.1-17.1); men: 16.2 (12.9-20.4); women: 6.2 (3.22-11.9)] but lower for lung [overall: 0.7 (0.6-0.9); men: 0.7 (0.5-0.8)], prostate [0.6 (0.5-0.7)], and breast cancers [0.6 (0.4-0.7)]. CONCLUSIONS: Spectrum of NADCs has changed, with prostate and breast cancers becoming the most common despite their lower SIR. IMPACT: These results confirm the need to maintain regular epidemiologic cancer monitoring in order to update screening guidelines.

Is the use of the QPC cognitive complaints questionnaire relevant for the screening strategy of HIV-Associated neurocognitive disorders?

BACKGROUND: The screening strategy for HIV-Associated Neurocognitive Disorders (HAND) is challenging. The French Expert Report recommend the use of the Cognitive Complaints Questionnaire (QPC) and the Montreal Cognitive assessment. However, the QPC has never been studied in People Living with HIV (PLWH). This study aims to determine the degree of agreement between QPC and the presence of HAND according to Frascati criteria, established by a battery of neuropsychological tests. METHODS: Data from patients who performed both a QPC and a battery of neuropsychological tests over a six-month follow-up period were evaluated retrospectively. RESULTS: A total of 121 patients were selected, with a median age of 53.1 years old. Among participants, 92.6% had an undetectable plasma viral load, 49.6% had a nadir CD4 less than 200/mm3 and 23.1% had a CDC stage C. Median CD4 cell count was 686/mm3. Prevalence of HAND was 57%, including 28.9% of Asymptomatic Neurocognitive Impairment, 24.8% of Mild Neurocognitive Disorder and 3.3% of HIV-associated Dementia. This analyze shows no agreement between QPC and HIV-associated neurocognitive disorders (kappa = -0.007). CONCLUSIONS: The QPC is not relevant in the screening for HAND. Thus, it urges to develop a specific tool to assess cognitive complaints among PLWH.

Hepatitis C virus-microelimination program and patient trajectories after hepatitis C virus cure in an outpatient HIV clinical unit.

OBJECTIVE: Treatment recommendations for hepatitis C now make no distinction between HIV/HCV-coinfected and HCV-monoinfected patients. The largest challenge remained lack of effective models to eliminate HCV in people living with HIV. We report the results of a microelimination program evaluating the possibility of eradicating HCV in an HIV-outpatient clinical unit within 12 months. METHODS: This HCV-microelimination program began in February 2016 in an unit following approximately 1000 HIV-infected patients and combined screening and therapeutic components according to the French guideline. A nested cohort study evaluating the impact of HCV cure on different health outcomes was conducted through self-administered questionnaires and using generalized mixed models. RESULTS: Among 601 patients eligible for HCV serological testing, 445 were evaluated, and two HCV acute infections were diagnosed. Among the 151 patients eligible for HCV RNA quantification, 119 were evaluated, and one reinfection with HCV was diagnosed. Among the 110 patients eligible for direct-acting antiviral treatment, 51 (46.4%) initiated treatment within the 12 months program, and 35 (31.8%) after. Sustained virologic response (SVR) rate was 96.1%, and two treatments failed. At least one self-reported symptom was declared by 72.5% (n = 29) of patients. Positive impact of HCV cure was observed on various markers of physical and mental health as well as on health habits. CONCLUSION: Our program should be considered as a proof of concept, which confirmed the feasibility of a HCV-microelimination program at the scale of an HIV clinical unit. However, 12 months were not sufficient to achieve our objective despite the specific organization.

Kaposi sarcoma in people living with HIV: incidence and associated factors in a French cohort between 2010 and 2015.

OBJECTIVE: Kaposi sarcoma is still observed among people living with HIV (PLHIV) including those on ART with undetectable HIV viral load (HIV-VL). We aimed to assess Kaposi sarcoma incidence and trends between 2010 and 2015 in France and to highlight associated factors. DESIGN: Retrospective study using longitudinal data from the Dat'AIDS cohort including 44 642 PLWH. For the incidence assessment, Kaposi sarcoma cases occurring within 30 days of cohort enrollment were excluded. METHODS: Demographic, immunological, and therapeutic characteristics collected at time of Kaposi sarcoma diagnosis or at last visit for patients without Kaposi sarcoma. RESULTS: Among 180 216.4 person-years, Kaposi sarcoma incidence was 76 (95% CI 64.3-89.9)/10 person-years. Multivariate analysis (Poisson regression) revealed the positive association with male sex, MSM transmission route, lower CD4 T-cell count, higher CD8 T-cell count, not to be on ART, whereas HIV follow-up time, duration with an HIV-VL 50 copies/ml or less were negatively associated with Kaposi sarcoma. According to the different models tested, HIV-VL, CD4 : CD8 ratio and nadir CD4 cell count were associated with Kaposi sarcoma. Moreover, stratified analysis showed that patients with a CD4 : CD8 ratio 0.5 or less or a CD8 T-cell count greater than 1000 cells/µl were at higher risk of Kaposi sarcoma regardless of the CD4 T-cell count. CONCLUSION: This study showed that in a resource-rich country setting with high ART coverage, Kaposi sarcoma still occurred among PLWH. CD8 hyperlymphocytosis and CD4 : CD8 ratio should be now considered as two useful markers to better identify patients at increased Kaposi sarcoma risk, including those with a CD4 T-cell count greater than 500 cells/µl.

Risk factors associated with overweight and obesity in HIV-infected people: Aging, behavioral factors but not cART in a cross-sectional study.

Identifying risk factors associated with overweight and obesity in HIV-infected patients.A cross-sectional study analyzing data from patients attending an HIV outpatient unit. Overweight was defined as body mass index (BMI) ≥25 kg/m; <30 kg/m, obesity was ≥30 kg/m. Patients' characteristics contemporary to BMI assessment were collected. Multivariate logistic regression identified risk factors associated with overweight/obesity.Eight hundred sixty-two patients, median age 51 years, 21.5 years of HIV infection follow-up, 585 (68%) male, 829 (96%) receiving combined antiretroviral therapy (cART) for median 16.7 years, 768 (91%) HIV load <40 copies/mL, 618 (73%) CD4 ≥500 cells/mm; 266 (31%) HCV serology, 110 (13%) had detectable HCV-RNA. Overweight affected 191 (22%) patients and obesity 46 (5%). Overweight and obesity were associated with age, HIV follow-up duration, and HIV transmission risk group. Overweight was also associated with gender and HCV status. In patients with substance use data, overweight was associated with alcohol and nonsmoking status. Obesity was associated with nonsmoking and ex-smoker status. Overweight/obesity were not found associated with cART or immune cell counts.In HIV-infected people, aging, alcohol consumption, nonsmoking, and ex-smoker status, the absence of HCV coinfection and to have cleared HCV infection are associated with overweight and/or obesity. Clinicians should be aware of these trends and consider introducing weight management programs as part of routine HIV care.

Ledipasvir and tenofovir drug interaction in human immunodeficiency virus-hepatitis C virus coinfected patients: Impact on tenofovir trough concentrations and renal safety.

We evaluate the impact of ledipasvir on both tenofovir plasma trough concentration and estimated glomerular renal function in human immunodeficiency virus-hepatitis C virus coinfected patients receiving a tenofovir-based antiretroviral regimen and treated with ledipasvir/sofosbuvir. Twenty-six patients [81% male, median age: 51 years; hepatitis C virus genotype 1(75%)/4(15%)] were included. Tenofovir trough concentration (interquartile range) increased from 78 ng ml-1 (53-110) at baseline to 141 ng ml-1 (72-176) at 1 month (P = 0.003). No significant difference on estimated glomerular renal function using both Cockroft-Gault and Modification of Diet in Renal Disease formulae, respectively, [median (interquartile range)] was observed between baseline [101.3 ml min-1 (91.1-114.1); 95.6 ml min-1 (86.5-111.2)], 1 month [102.4 ml min-1 (89.8-112.9), P = 0.26; 92.5 ml min-1 (88.1-114.3), P = 0.27], end-of-treatment [96.5 ml min-1 (82.4-115.4), P = 0.39; 95.4 ml min-1 (84.2-105.4), P = 0.16] and 12 weeks after the end of treatment [100.5 ml min-1 (83.3-111.9), P = 0.24; 93.4 ml min-1 (82.2-103.5), P = 0.16]. Three patients progressed from chronic kidney disease stage 1 to stage 2 at 12 weeks post-treatment. A significant increase in tenofovir exposure through P-glycoprotein inhibition by ledipasvir was confirmed without significant impact on glomerular renal function in our population with normal renal function or mild renal impairment.

Impact of tenofovir dose adjustment on both estimated glomerular filtration rate and tenofovir trough concentration.

BACKGROUND: Tenofovir disoproxil fumarate (TDF)-based regimen is a treatment option for HIV-infected patients. TDF dose adjustment is recommended in patients with impaired renal function. We assessed the impact of TDF dose adjustment on renal function and tenofovir trough concentration. METHODS: Fourteen HIV patients for whom TDF dose was adjusted (1 tablet/48 h) because of estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, and/or due to a tenofovir trough concentration >90 ng/ml between 2006 and 2013 were selected. The eGFR was measured at baseline and 3, 6 and 12 months after TDF dose adjustment. RESULTS: A 50% TDF dose reduction resulted in a significant increase of the eGFR 3 months after dose adjustment (61.1 versus 72.8 ml/min/1.73 m2; P=0.003). Concomitantly, tenofovir trough concentration decreased from 175 to 66 ng/ml (P=0.009). Antiviral efficacy was maintained in all patients. CONCLUSIONS: TDF dose adjustment combined with therapeutic drug monitoring may be useful especially in patients at risk of kidney dysfunction.

First-line cART regimen impacts the course of CD8+ T-cell counts in HIV-infected patients that achieve sustained undetectable viral load.

The aim of the study was to investigate the impact of first-line combined antiretroviral therapy (cART) regimen on the course of CD8 T-cell counts in human immunodeficiency virus (HIV)-infected patients.A retrospective observational study conducted on the French DAT'AIDS Cohort of HIV-infected patients.We selected 605 patients initiating a first-line cART between 2002 and 2009, and which achieved a sustained undetectable HIV plasma viral load (pVL) for at least 12 months without cART modification. The evolution of CD8 T-cell counts according to cART regimen was assessed.CD8 T-cell counts were assessed in 572 patients treated with 2NRTIs+1PI/r (n= 297), 2NRTIs+1NNRTI (n= 207) and 3NRTIs (n= 68). In multivariate analysis, after 12 months of follow-up, the 3NRTIs regimen was associated with a significantly smaller decrease of CD8 T-cell count compared with NNRTI-containing regimens (-10.2 cells/µL in 3NRTIs vs -105.1 cells/µL; P=0.02) but not compared with PI-containing regimens (10.2 vs -60.9 cells/µL; P=0.21). After 24 months, the 3NRTIs regimen was associated with a smaller decrease of CD8 T-cell count and % compared with PI/r- and NNRTI-containing regimens (0.2 in 3NRTIs vs -9.9 with PI/r-regimens, P=0.001, and vs -11.1 with NNRTI-regimens, p < 0.0001). A focus analysis on 11 patients treated with an INSTI-containing cART regimen during the study period showed after 12 months of follow-up, a median decrease of CD8 T-cell count of -155 [inter quartile range: -302; -22] cells/µL.Our data highlight the fact that cART regimens have differential effects on CD8 pool down regulation.

Potential for Drug-Drug Interactions between Antiretrovirals and HCV Direct Acting Antivirals in a Large Cohort of HIV/HCV Coinfected Patients.

OBJECTIVES: Development of direct acting antivirals (DAA) offers new benefits for patients with chronic hepatitis C. The combination of these drugs with antiretroviral treatment (cART) is a real challenge in HIV/HCV coinfected patients. The aim of this study was to describe potential drug-drug interactions between DAAs and antiretroviral drugs in a cohort of HIV/HCV coinfected patients. METHODS: Cross-sectional study of all HIV/HCV coinfected patients attending at least one visit in 2012 in the multicenter French Dat'AIDS cohort. A simulation of drug-drug interactions between antiretroviral treatment and DAAs available in 2015 was performed. RESULTS: Of 16,634 HIV-infected patients, 2,511 had detectable anti-HCV antibodies, of whom 1,196 had a detectable HCV-RNA and were not receiving HCV treatment at the time of analysis. 97.1% of these patients were receiving cART and 81.2% had a plasma HIV RNA <50 copies/mL. cART included combinations of nucleoside reverse transcriptase inhibitors with a boosted protease inhibitor in 43.6%, a non-nucleoside reverse transcriptase inhibitor in 17.3%, an integrase inhibitor in 15.4% and various combinations or antiretroviral drugs in 23.7% of patients. A previous treatment against HCV had been administered in 64.4% of patients. Contraindicated associations/potential interactions were expected between cART and respectively sofosbuvir (0.2%/0%), sofosbuvir/ledipasvir (0.2%/67.6%), daclatasvir (0%/49.4%), ombitasvir/boosted paritaprevir (with or without dasabuvir) (34.4%/52.2%) and simeprevir (78.8%/0%). CONCLUSIONS: Significant potential drug-drug interactions are expected between cART and the currently available DAAs in the majority of HIV/HCV coinfected patients. Sofosbuvir/ledipasvir and sofosbuvir/daclatasvir with or without ribavirin appeared the most suitable combinations in our population. A close collaboration between hepatologists and HIV/AIDS specialists appears necessary for the management of HCV treatment concomitantly to cART.

Impact of hepatitis C virus coinfection on T-cell dynamics in long-term HIV-suppressors under combined antiretroviral therapy.

OBJECTIVE: The objective of this study is to evaluate the impact of hepatitis C virus (HCV) serostatus on the evolution of CD8 cells and CD4 : CD8 ratio in HIV-infected patients on combined antiretroviral therapy (cART) who achieve sustained undetectable viral load (HIV-pVL). DESIGN AND METHODS: A longitudinal study performed in an outpatient HIV-unit following 1495 HIV-infected patients. Data of patients on cART achieving undetectable HIV-pVL for at least 3 years were collected retrospectively from our medical e-database NADIS from January 1997 to April 2005, a period defined in order to select patients who were naive of hepatitis treatment. T-cell counts were assessed every 6 months from HIV-suppression over the study period. RESULTS: Two hundred and twenty-six HIV mono-infected (group 1) and 130 HCV-coinfected patients (group 2; genotype prevalence: 42% HCV-G1, 26% HCV-G3, 11% HCV-G4 and 21% HCV-G2) fulfilled the selection criteria. cART regimens were comparable between the groups, as were CD4 and CD8 cell counts at the first undetectable HIV-pVL. After 3 years, both groups displayed similar CD4 cell reconstitution, although CD4 percentage was higher in group 1 (30.3 ±â€Š1.1 vs. 27 ±â€Š1.1%; P < 0.001). HIV suppression led to a significant drop of median CD8 cell counts in group 1 (P = 0.027), but not in group 2, which displayed higher CD8 cell counts all through the follow-up (mean diff. = 135.71 ±â€Š26.89 cells/µl, P < 0.001). Moreover, the fraction of patients reaching CD4 : CD8 ratio ≥ 1 was lower in group 2 (14 vs. 27.7%; P < 0.05). CONCLUSION: Despite sustained HIV suppression under cART, HCV coinfection was found to hamper CD8 downregulation. Further studies will determine the impact of treatment with direct-acting antiviral agents on the CD8 pool, and the advantage of systematic HCV-targeted therapy for HIV/HCV-coinfected patients.

Distribution of human papillomavirus genotypes, assessment of HPV 16 and 18 viral load and anal related lesions in HIV positive patients: a cross-sectional analysis.

Natural history of anal intraepithelial neoplasia and anal cancer is not fully understood. Factors associated with cytological abnormalities and predictors of progression to high-grade anal intraepithelial neoplasia still deserve investigation. The aim of this cross-sectional study was to assess the prevalence of HPV types, the relationship between HPV genotypes, HPV 16/18 viral load and cytological abnormalities in male and female HIV-infected patients. One hundred and twenty-two (72.6%) patients were infected with HPV, 75 (61%) had multiple HPV infection, and 94 (77%) had high-risk HPV infection. The most frequently identified HPV types were HPV 16 (64%), HPV 6 (39%), HPV 18 (31%), HPV 53 (14.7%), HPV 33 (10.6%), HPV 11 (8.2%), HPV 70 (5.7%), and HPV 61 (4.9%). The HPV types which were most frequently found in combination were HPV 6 + 16 (9.8%), 6 + 16 + 18 (8.2%), 16 + 18 (6.6%), 6 + 18 (4.9%), 16 + 33 (3.3%), 16 + 53 (3.3%). Median HPV16 and 18 viral loads were 6.1 log10 copies/10(6) cells [IQR 5.0-7.3] and 6.1 log10 copies/10(6) cells [IQR 5.7-6.0], respectively. Male gender (P = 0.03, OR: 1.2 [1.0-1.4]) and homo/bisexual transmission routes (P = 0.044, OR: 1.4 [1.0-1.9]) were associated with HPV 16 infection. An HPV 16 viral load cut-off ≥5.3 log10 copies/10(6) cells and a CD4+ cell count ≤200/µl were independent factors associated with abnormal cytology. In the absence of national consensus guidelines, a strict regular follow-up at shorter intervals is recommended for HIV-infected patients with abnormal cytology, especially low grade squamous intraepithelial lesions, an HPV 16 viral load ≥5.3 log/10(6) cells and a CD4+ cell count ≤200/µl.

Lack of correlation between the size of HIV proviral DNA reservoir and the level of immune activation in HIV-infected patients with a sustained undetectable HIV viral load for 10 years.

BACKGROUND: The persistence of HIV residual replication in patients with an undetectable plasma viral load (pVL) may limit immune recovery and facilitate inflammation-induced comorbidities. OBJECTIVE: The objective was to evaluate any correlation between immune restoration and intracellular [IC] HIV-DNA in cART-treated patients with a sustained undetectable pVL. STUDY DESIGN: This retrospective cross sectional study included 62 patients with a median duration of undetectable pVL of 10.3 years. IC HIV DNA in peripheral mononuclear blood cells (PBMCs) and T cell subsets were measured at the last visit. pVL, CD4(+) and CD8(+) T cell counts were retrospectively collected from the onset of long-term inhibition by antiretroviral treatment. The patients were separated into two groups: 27 non-blippers (sustained pVL< threshold value during all the visits) and 35 blippers ( ≥ 1 episodes of pVL> threshold but < 1000 copies/ml). The median pVL in blippers was 115 copies/ml. RESULTS: The median IC HIV DNA rate was 34 copies/10(6) PBMCs (71% ≥ 20 copies/10(6) PBMCs) with no significant difference between the groups. The proportion of CD8(+)CD38(+) and CD8(+)DR(+) T cells was higher in blipper patients, but the difference was only significant for the CD8(+)DR(+) marker (p = 0.036). No correlation was found between markers of immune activation on CD4(+) and CD8(+) T cells and the IC HIV-DNA level. CONCLUSION: No relation was found between the size of HIV reservoirs and immune activation in patients with sustained undetectable pVL. Mechanisms of immune activation have to be better understood in order to define specific therapeutic interventions.

Renal impairment in patients receiving a tenofovir-cART regimen: impact of tenofovir trough concentration.

OBJECTIVE: Tenofovir disoproxil fumarate (TDF) is known to induce renal dysfunction in HIV-infected patients. The aim of this retrospective study was to evaluate the correlation between TDF trough concentration (Ctrough-TDF) and glomerular filtration rate (GFR) in a cohort of patients on antiretroviral therapy. METHODS: A total of 163 patients with at least one determination of Ctrough-TDF between 17-24 hours were retrospectively selected from a computerized database and distributed into 3 groups defined by TDF concentrations <40 (11.7%), between 40 and 90 (36.8%), and >90 (high-level group, 51.5%) ng/mL. GFR was measured by Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration formulae at the times of TDF initiation and Ctrough-TDF determination and after 12 months. RESULTS: At the time of Ctrough-TDF measurement, median duration of TDF-based therapy was 21.1 months. GFR was significantly decreased in high-level group (-8.5 mL/min; P < 0.001) whatever the method used. GFR decline was significantly associated with an older age. Gender-stratified analysis showed that the early impact of Ctrough-TDF >90 ng/mL was significant in women only. After 12 months, the decrease in GFR in patients with high Ctrough-TDF was observed in both men and women (-8.27; P = 0.003). CONCLUSIONS: The high prevalence of elevated Ctrough-TDF and its correlation with an increased risk of renal impairment support the usefulness of therapeutic drug monitoring for TDF, particularly in women and older patients.

High level of HPV 16 and 18 DNA load in anal swabs from male and female HIV-1 infected patients.

BACKGROUND: Despite HAART, the prevalence and incidence of anal cancer in HIV-infected individuals have increased. Recently, the relationship between the severity of cervical lesions and oncogenic HPV load was demonstrated; however, few studies have assessed the level and the significance of oncogenic HPV load in patients at risk for anal neoplasia. OBJECTIVES: To assess HPV genotypes and HPV 16/18 DNA load in HIV-1 infected patients at risk for anal neoplasia. STUDY DESIGN: Cross-sectional pilot study from male and female HIV-1 infected individuals at risk for anal neoplasia in an outpatient HIV Clinical Unit of Marseilles university Hospitals. RESULTS: Anal HPV was found in 79% of the patients whereas high-risk (HR) HPV types and infection with multiple HPV types were found in 83% and 61% of the patients, respectively. Using a sensitive real-time PCR, median HPV 16 and 18 DNA load were 5 x 10(6) copies/10(6) cells and 3.2 x 10(5) copies/10(6) cells, respectively. Notably, there were no significant differences in the HPV 16/18 viral loads with respect to the anoscopic results. CONCLUSIONS: Longitudinal studies are needed to evaluate the link between high anal HPV DNA load and progression to anal squamous intraepithelial lesions and anal cancer.