Anja Potthoff

Anal carcinoma in human immunodeficiency virus-positive men: results of a prospective study from Germany

Background  Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)‐associated potential precursor lesion of anal cancer, is frequent among human immunodeficiency virus (HIV)‐positive men who have sex with men (MSM). There is a paucity of data published on the progression of high‐grade AIN to invasive cancer as well as on clinical and virological characteristics comparing anal margin and anal canal carcinoma.

Imiquimod leads to a decrease of human papillomavirus DNA and to a sustained clearance of anal intraepithelial neoplasia in HIV-infected men.

Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)-associated precursor lesion of anal carcinoma, is highly prevalent in HIV-infected men having sex with men (MSM). This prospective follow-up study evaluated the long-term results of imiquimod treatment of AIN in 19 HIV-infected MSM. Standardized follow-up examinations included high-resolution anoscopy, anal cytology/histology, HPV typing, and DNA load determination for HPV types 16, 18, 31, and 33. Mean follow-up time was 30.3 months. A total of 74% (14/19) of the patients remained free of AIN at the previously treated site. Five patients (26%) had recurrent high-grade AIN after a mean time of 24.6 months. At the end of follow-up, the numbers of HPV types as well as high-risk HPV-DNA loads were significantly lower than before therapy. During follow-up, 58% of all patients (11/19) developed new anal cytological abnormalities in previously normal, untreated anal regions. 55% of these new AIN lesions were high-grade lesions and most of them were located intra-anally and associated with high-risk HPV types not detectable before therapy. These results demonstrate that imiquimod leads to a high rate of long-term clearance of AIN in HIV-positive men together with a prolonged decrease of high-risk HPV-DNA load. However, new AIN lesions associated with previously undetected HPV types frequently occur in untreated areas.

Are HIV patients undertreated? Cardiovascular risk factors in HIV: results of the HIV-HEART study.

Background: Antiretroviral therapy improved the survival of patients with human immunodeficiency virus (HIV) infection. With increased life expectancy, HIV-infected patients increasingly are experiencing comorbidities, most notably cardiovascular risk factors (CRFs) and coronary heart disease (CHD). Design: This study utilized a prospective, cross-sectional multicentre long-term design. Methods: In 803 patients (82% male; mean age 44.2 ± 10.3 years) we evaluated the prevalence of CRFs and 10-year risk of CHD using the Framingham risk model. The presence of a risk factor was determined based on the guidelines of the National Cholesterol Education Program (NCEP ATP III), the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), and the German Society of Cardiology. Results: The most common CRFs were smoking (51.2%), high triglycerides (39.0%), low high-density lipoprotein cholesterol (27.5 %) and high blood pressure (21.4%). In total, 60.3%, 21.6%, and 18.1% of patients were categorized as being at low (<10%), moderate (10–20%), and high (>20%) 10-year risk for CHD, respectively. In patients with hypertension, at least one antihypertensive drug was given in 91/163 (55.8%) patients. The percentage of patients on treatment with diabetes mellitus was 23/41 (56.1%). Anti-platelet therapy was prescribed to 42/102 (41.2%) patients with known CHD or CHD equivalent. In patients of moderate or high CHD risk there were more than 50% and 30% for LDL cholesterol and more than 60% and 40% for total cholesterol untreated. Conclusions: The prevalence of CRFs remains high in an HIV-infected population. CRF management of HIV-infected patients deserves further improvement.

Topical 5-fluorouracil treatment of anal intraepithelial neoplasia in human immunodeficiency virus-positive men

Background  Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)‐induced potential precursor lesion of anal cancer, is frequent among human immunodeficiency virus (HIV)‐positive men who have sex with men (MSM). So far, only a few prospective studies have been performed on the topical treatment of AIN, especially at the intra‐anal location.

Prevalence of Cardiac Diastolic Dysfunction in HIV-Infected Patients: Results of the HIV-HEART Study

Abstract Purpose: Antiretroviral therapy has improved the prognosis for many individuals with HIV infection. Consequently, HIV infection has become a chronic and manageable disease with increased risk of cardiovascular disease. Isolated diastolic dysfunction (DD) may be the first indication of underlying cardiac disease and an early marker of coronary artery disease. Our aim was to assess the prevalence of DD in HIV-infected patients. Methods: In this cross-sectional cohort study, 698 unselected patients were included. All subjects underwent two-dimensional transthoracic echocardiography with tissue Doppler imaging. Results: The prevalence of DD among the HIV-infected patients was 48%. Patients with DD were characterized by older age, higher body mass index, higher total cholesterol, arterial hypertension, and diabetes mellitus. Diabetes mellitus and arterial hypertension were associated with approximately four times the risk for DD (odds ratio [OR] 3.9, 95% CI 1.65–9.17; OR 3.8, 95% CI 2.49–5.71, respectively). Persons with hyperlipidemia were approximately one and a half times more likely to have DD than those without hyperlipidemia (OR 1.5, 95% CI 1.12–2.07). Conclusions: In our study, an impressive high prevalence of DD in HIV-infected patients was demonstrated. Traditional cardiovascular risk factors substantially contributed to the development of DD in the HIV-infected cohort.

Merkel Cell Polyomavirus Infection in HIV-Positive Men

OBJECTIVE To evaluate Merkel cell polyomavirus (MCPyV) DNA prevalence and load among men with human immunodeficiency virus (HIV) (hereafter referred to as HIV-positive men) and among healthy male control subjects. DESIGN Prospective study from February 4, 2009, through April 24, 2010. SETTING Dermatology department of a university hospital. PATIENTS A total of 449 male adults were prospectively recruited, including 210 HIV-positive men who have sex with men and 239 healthy controls. Cutaneous swabs were obtained once from the surface of the forehead in all participants. MAIN OUTCOME MEASURES Swabs were evaluated for the presence of MCPyV DNA using single-round and nested polymerase chain reaction. The MCPyV DNA load (the number of MCPyV DNA copies per β-globin gene copy) was determined in MCPyV-positive samples using quantitative real-time polymerase chain reaction. RESULTS Among 449 forehead swabs analyzed, MCPyV DNA was detected in 242 (53.9%). Compared with healthy controls, HIV-positive men more frequently had MCPyV DNA on nested polymerase chain reaction (49.4% vs 59.0%, P = .046) and on single-round polymerase chain reaction (15.9% vs 28.1%, P = .002). The MCPyV DNA loads in HIV-positive men were similar to those in HIV-negative men, but HIV-positive men with poorly controlled HIV infection had significantly higher MCPyV DNA loads than those who had well-controlled HIV infection (median and mean MCPyV DNA loads, 2.48 and 273.04 vs 0.48 and 11.84; P = .046). CONCLUSIONS Cutaneous MCPyV prevalence is increased among HIV-positive men who have sex with men. Furthermore, MCPyV DNA loads are significantly higher in HIV-positive men with poorly controlled HIV infection compared with those who have well-controlled HIV infection. This could explain the increased risk of MCPyV-associated Merkel cell carcinoma observed among HIV-positive individuals.

Uridine supplementation enhances hepatic mitochondrial function in thymidine-analogue treated HIV-infected patients.

Supplementation with uridine offers the possibility of a new and promising approach to nucleoside analogue reverse transcriptase inhibitor-associated mitochondrial toxicity. We investigated the metabolic effects of short-course treatment with the uridine-enriched food supplement NucleomaxX on hepatic mitochondrial function in thymidine-analogue treated HIV-infected patients. Mitochondrial function was assessed by a recently introduced non-invasive 13C-methionine breath test. NucleomaxX supplementation enhanced mitochondrial decarboxylation function reversibly but reproducibly in all patients. Repeated administration in shorter treatment intervals may maintain this effect.

Human polyomaviruses 6, 7, 9, 10 and Trichodysplasia spinulosa-associated polyomavirus in HIV-infected men

Recently, several novel human polyomaviruses (HPyVs) have been detected. HPyV6, 7, 9 and 10 are not associated with any disease so far. Trichodysplasia spinulosa (TS)-associated polyomavirus (TSPyV) can cause the rare skin disease TS. We have evaluated cutaneous DNA prevalence and viral loads of five HPyVs in HIV-infected men compared to healthy male controls. 449 forehead swabs were analysed by HPyV-specific real-time PCR. HPyV6, HPyV7, TSPyV and HPyV10 were found significantly more frequently on the skin of 210 HIV-infected compared to 239 HIV-negative men (HPyV6, 39.0 vs 27.6 %; HPyV7, 21.0 vs 13.4 %; TSPyV, 3.8 vs 0.8 %; HPyV10, 9.3 vs 3.4 %; P<0.05, respectively). HPyV9 was not detected. Multiple infections were more frequent in HIV-positive men, but HPyV-DNA loads did not differ significantly in both groups. In contrast to HPyV6, 7 and 10, TSPyV and HPyV9 do not seem to be a regular part of the human skin microbiome.

Human papillomavirus-associated induction of human β-defensins in anal intraepithelial neoplasia

Background  Antimicrobial peptides and proteins (AMPs) are widely distributed effector molecules of the innate immune system with well‐known antibacterial activity. However, there is a paucity of information regarding antiviral effects of AMPs.

p16ink4a expression decreases during imiquimod treatment of anal intraepithelial neoplasia in human immunodeficiency virus-infected men and correlates with the decline of lesional high-risk human papillomavirus DNA load

Background  Human papillomavirus (HPV)‐associated anogenital cancers and their precursor lesions occur in excess in human immunodeficiency virus (HIV)‐infected patients despite the initiation of highly active antiretroviral therapy. In this context, a drastically increased relative risk for anal intraepithelial neoplasia (AIN) exists in HIV‐infected men having sex with men (MSM). In a pilot study, imiquimod, a topical immune response modifier, has been reported to be beneficial in the treatment of AIN.