Josep Coll

Gut Microbiota Linked to Sexual Preference and HIV Infection

The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction.

Natural history of human papillomavirus infections involving anal, penile, and oral sites among HIV-positive men.

Aim The aim of this study was to characterize the natural history of human papillomavirus (HPV) infection at anal canal, penile, and oral sites in HIV-positive men based on their sexual behavior. Methods This is a single-center, prospective cohort study. The prevalence, clearance, and incidence of HPV infection at anal, penile, and oral sites were studied in HIV-positive men who have sex with men (MSM) and heterosexual individuals using multiplex polymerase chain reaction. Risk factors associated with HPV infection were analyzed. Results In total, 733 patients (538 MSM, 195 heterosexual) were included in the study between 2005 and 2009. The prevalence, clearance, and incidence of HPV infection were 73%, 30%, and 36% at anal site; 26%, 56%, and 17% at penile site; and 16%, 44%, and 11% at oral site, respectively. At anal site, MSM had a higher HPV prevalence (84% vs. 42%; odds ratio,7.3; 95% confidence interval [CI], 5.2–10.6) mainly for multiple (≥3) HPV types, higher incidence rate (324 vs. 92 new HPV-infected person per 1000 person-years [hazard ratio, 8.1; 95% CI, 3.8–17.3]), and a lower clearance rate (125 vs. 184 cleared HPV-infected person per 1000 person-years [hazard ratio, 0.5; 95% CI, 0.3–0.9]) than did heterosexuals. Similar prevalence, clearance, and incidence rates of penile and oral HPV infection were found between groups. The most common high-risk HPV type for the 3 body sites studied was the HPV-16. Finally, a similar proportion of heterosexuals (7%) and MSM (6%) presented concurrent HPV infections (anal-penile-oral sites). History of anal warts was associated with higher HPV prevalence in the 3 body parts. Conclusions Although MSM presented the highest risk of anal HPV infection, heterosexual men also showed a remarkable prevalence of anal HPV infection and a comparable risk to MSM for penile and oral HPV infection. Taking into account all these results, the careful inspection of the anal canal, penile, and oral sites should at least be routine in each clinic visit of HIV-infected men independently of their sexual behavior.

Prevalence, clearance, and incidence of human papillomavirus type-specific infection at the anal and penile site of HIV-infected men.

Background We studied the type-specific infection of human papillomavirus (HPV) at the anal canal and penile site in a cohort of HIV-infected men. Methods Prevalence, clearance, and incidence of specific HPV types in the anal canal and penis were determined in 733 HIV-infected men from the Spanish CAn Ruti HIV+ Men ([CARH•MEN]) cohort (538 men who have sex with men [MSM] and 195 heterosexual men). Results In both groups, the most prevalent high-risk type was HPV-16 (anal canal [31.6% MSM; 6.8% heterosexual] and penis [4.8% MSM; 6.8% heterosexual]). The most prevalent low-risk type was HPV-6 (anal canal [23.2% MSM; 12.8% heterosexual], penis [8.1% MSM; 8.9% heterosexual]). Anal prevalence was significantly higher in MSM, as was incidence, except for HPV-16, which was similar between male groups (5.9 new cases per 1000 person-months [95% confidence interval, 4.3–7.9] in MSM; 4.4 [95% confidence interval, 2.5–7.2] in heterosexual men; P > 0.05). The anal clearance rate of the different HPV types and retention time of infection were similar in both groups, as well as the HPV infection of the penis. Conclusions HIV-infected MSM had a high prevalence of HPV infection at the anal canal; however, heterosexual HIV-infected men were also at risk for acquiring and sustaining persistent high-risk HPV types at the anal and penile site and are at risk for developing dysplasia in the future. All HIV-infected men should be recommended for routinely anal HPV screening.

Distribution of human papillomavirus genotypes in anal cytological and histological specimens from HIV-infected men who have sex with men and men who have sex with women.

BACKGROUND: Anal cancer is caused by human papillomavirus (HPV). Moreover, human immunodeficiency virus (HIV) is an additional risk factor for anal cancer. Therefore, when designing preventive protocols for HIV-infected men, it is important to detect high-risk (HR) oncogenic HPV genotypes present in their anal canals. However, most studies have focused only on men who have sex with men (MSM). OBJECTIVE: To estimate the prevalence of HPV and describe its genotype distribution using anal cytology and histology specimens from HIV-infected populations of MSM and men who have sex with women (MSW). DESIGN: Crosssectional study of the CARH·MEN cohort. SETTING: Single-center prospective cohort of HIV-infected men attending the Outpatient HIV Clinic of Hospital Germans Trias i Pujol (Spain), where they undergo annual screening for HPV infection of the anus, penis and mouth. PATIENTS: Four hundred eighty-three HIV-infected men (341 MSM, 142 MSW) with no current or previous history of anal condylomata. MAIN OUTCOME MEASURES: HPV genotypes detected (multiplex-PCR), cytology results (Papanicolaou test) and histology results (biopsy-based). RESULTS: Cytological abnormalities were detected in 40% of MSM (129/321; 95%CI, 35–46) and 20% of MSW (26/131; 95%CI, 13–28) (OR=2.7; 95%CI, 1.7–4.4). All high-grade squamous intraepithelial lesions (HSIL) were positive for HR-HPV in both groups. High-resolution anoscopy was performed in 146 patients (120 MSM, 26 MSW) with abnormal cytological diagnoses. Lesions were visualized in 80 MSM (67%) and 14 MSW (54%) (OR=1.7 [95%CI, 0.7–4.0]). Histological diagnosis was anal intraepithelial neoplasia (AIN)-1 in 51 MSM (64%) and 6 MSW (43%), AIN-2 in 9 MSM (11%) and 3 MSW (21%), AIN-3 in 7 MSM (9%) and 1 MSW (7%), and normal in 13 MSM (16%) and 4 MSW (29%). HPV16 was the most prevalent HR genotype. LIMITATIONS: Study limitations include its crosssectional design. CONCLUSIONS: Anal cancer screening should be offered to all HIV-infected men, regardless of their sexual orientation.

Condylomata, cytological abnormalities and human papillomavirus infection in the anal canal in HIV-infected men

Genital infections with low‐risk (LR) and high‐risk (HR) human papillomavirus (HPV) genotypes are associated with ano‐genital condylomata and anal squamous cell cancer. HPV‐related pathologies in HIV‐infected men are a serious concern. In this study, the prevalence of anal condylomata and their association with cytological abnormalities and HPV infection in the anal canal in HIV‐infected men [men who have sex with men (MSM) and heterosexuals] were estimated.

Long-term effectiveness of infrared coagulation for the treatment of anal intraepithelial neoplasia grades 2 and 3 in HIV-infected men and women.

Aims:To assess the effectiveness and safety of infrared coagulation (IRC) for the ablation of anal intraepithelial neoplasia (AIN) and to provide data on the prevalence of AIN in HIV-infected patients. Patients and methods:We performed a single-center, retrospective cohort study based on data collected from a prospectively compiled database of outpatients attended in the Clinical-Proctology-HIV-Unit (first visit). The effectiveness (normal anal cytology after 12 months of IRC) and safety of IRC were estimated. Results:Between January 2005 and December 2011, a total of 69 (5%) patients with biopsy-proven AIN-2 or AIN-3 from among 1518 patients (1310 men; 208 women) were treated with IRC. The prevalence of cytological abnormalities was 49.5% [751/1518; (atypical squamous cells of unknown significance, 14%; low-grade squamous intraepithelial lesions, 27.5%; high-grade squamous intraepithelial lesions, 8%)]. High-resolution anoscopy revealed intra-anal condylomata in 31% of patients (236/751), nonvisualized lesions in 30% (227/751), and visualized lesions (from which biopsy specimens were taken) in 38% (288/751). The histological diagnosis was: AIN-1, 52% (151/288); AIN-2, 15% (44/288); AIN-3, 9% (25/288); normal, 19% (56/288); and nonevaluable, 4% (12/288). IRC was applied in-office in 66 patients (three refused to undergo treatment). At 12 months, all patients (n = 56) had a normal anal cytology result. Seven (13%) patients had biopsy-proven recurrence [mean (range) time-to-recurrence, 30 (18–43) months]. High-risk-human papilloma virus (HPV) infection was detected in all anal lesions (HPV-16 was the most common genotype). Agreement between cytological and histological results was poor. Conclusion:A high prevalence of AIN was found in both HIV-infected men and HIV-infected women. Although randomized clinical trials are lacking, IRC ablation of AIN-2 and AIN-3 lesions without concomitant condylomata could help prevent anal squamous cell carcinoma.

Reduced darunavir dose is as effective in maintaining HIV suppression as the standard dose in virologically suppressed HIV-infected patients: a randomized clinical trial

OBJECTIVES Maximizing ART efficiency is of growing interest. This study assessed the efficacy, safety, pharmacokinetics and economics of a darunavir dose-reduction strategy. METHODS This was a multicentre, randomized, open-label clinical trial in HIV-infected patients with plasma HIV-1 RNA <50 copies/mL while receiving triple ART including 800 mg of darunavir once daily. Participants were randomized to continue 800 mg of darunavir (DRV800) or to 600 mg of darunavir (DRV600), both once daily. Treatment failure was defined as two consecutive HIV-1 RNA determinations >50 copies/mL or discontinuation of study treatment by week 48. The study was registered at https://www.clinicaltrialsregister.eu (trial number 2011-006272-39). RESULTS Fifty participants were allocated to each arm. The mean (SD) CD4+ T cell count at baseline was 562 (303) cells/mm(3) and HIV-1 RNA had been <50 copies/mL for a median (IQR) of 106.9 (43.4-227.9) weeks before enrolment. At week 48 no treatment failure had occurred in 45/50 (90%) DRV600 patients and in 47/50 (94%) DRV800 patients (difference -4%; 95% CI lower limit, -12.9%). When only patients with virological data were considered, that endpoint was met by 45/48 (94%) in the DRV600 arm and 47/49 (96%) in the DRV800 arm (difference -2.2%; 95% CI lower limit, -9.6%). Darunavir exposure was similar in the two arms. The average reduction in annual cost per successfully treated DRV600-arm patient was US

Oral human papillomavirus type-specific infection in HIV-infected men: a prospective cohort study among men who have sex with men and heterosexual men.

7273. CONCLUSIONS The efficacy of a darunavir daily dose of 600 mg seemed to be similar to the efficacy of the standard 800 mg dose in virologically suppressed HIV-infected patients on triple ART. This strategy can potentially translate to substantial savings in the cost of care of HIV-infected patients.

Human papillomavirus genotype distribution and human papillomavirus 16 and human papillomavirus 18 genomic integration in invasive and in situ cervical carcinoma in human immunodeficiency virus-infected women.

The natural history of type-specific oral infection of human papillomavirus (HPV) was assessed in a cohort of HIV-infected men (538 men who have sex with men (MSM); 195 heterosexuals). Risk factors associated with oral HPV infections were examined. The overall prevalence of HPV was 16%: HPV-16 was the most prevalent type (3.7% MSM; 7.8% heterosexuals). The prevalence of HPV-16 in heterosexuals was associated with CD4 nadir counts <200 cells/μL (ORadjusted = 3.0, 95% CI, 1.4-6.3). The overall incidence of HPV was similar between groups (11%), but the incidence of HPV-16 was higher in heterosexuals (ORadjusted = 3.2, 95% CI, 1.1-9.5). Not only MSM but also HIV-infected heterosexual men are at risk of HPV infection. Regular and careful oral inspection is needed.

Comparison of the f-HPV typing™ and Hybrid Capture II® assays for detection of high-risk HPV genotypes in cervical samples

Background: Women infected with human immunodeficiency virus (HIV) are at increased risk of developing precancerous and cancerous lesions in cervix because of persistence of oncogenic human papillomavirus (HPV) infection. Scarce information about the HPV genotypes attributed to cervical cancer in the HIV-infected population is available, especially in countries with a low prevalence of this pathology. Objective: The objective of the study was to assess the prevalence and distribution of HPV types, and the viral integration of HPV-16 and HPV-18 in cervical squamous cell carcinoma of HIV-infected and HIV-negative women. Methods: A total of 140 formaldehyde-fixed paraffin-embedded specimens from 31 HIV-infected and 109 matched HIV-negative women, with a diagnosis of in situ or invasive cervical carcinoma, were identified between 1987 and 2010 from different hospitals of the Barcelona area, Spain. Human papillomavirus genotyping and integration were analyzed by standardized polymerase chain reaction. Results: Similar prevalence and distribution of HPV genotypes were detected in cervical cancers (in situ and invasive) regardless of HIV condition. The most common types were as follows: HPV-16 (58% in HIV-positive vs 72% in HIV-negative) and HPV-33 (16% vs 8%). In invasive cervical carcinoma, HPV-18 was significantly more prevalent in HIV-positive women (14% vs 1%; P = 0.014). The proportion of samples with integrated forms of HPV-16 (39% vs 45%) and HPV-18 (50% vs 50%) was similar in both groups. Conclusions: The prevalence and distribution of principal HPV types involved in the carcinogenesis process of the cervix were similar in HIV-infected and noninfected women, although a tendency toward a lower HPV-16 and a higher HPV-18 prevalence in invasive cervical carcinoma was detected in HIV-positive women. Similar percentage of HPV-16 and HPV-18 viral integration was found in formaldehyde-fixed paraffin-embedded specimens of cervical cancer regardless of the HIV infection status.