Uninfected Homosexual Men Research Articles

A Composite Cytology–Histology Endpoint Allows a More Accurate Estimate of Anal High-Grade Squamous Intraepithelial Lesion Prevalence

There is debate about the accuracy of anal cytology and high-resolution anoscopy (HRA), in the diagnosis of anal human papillomavirus (HPV)-related squamous intraepithelial lesions (SIL). Few studies have performed both simultaneously in a large sample of high-risk individuals. At baseline in a community-based cohort of HIV-infected and uninfected homosexual men ages ≥35 years in Sydney, Australia, all men underwent anal swabbing for cytology and HPV genotyping, and HRA-guided biopsy. We evaluated the separate and combined diagnostic accuracy of cytology and histology, based on a comparison with the prevalence of HPV16 and other high-risk (HR) HPV. We examined trends in HPV prevalence across cytology-histology combinations. Anal swab, HRA, and HPV genotyping results were available for 605 of 617 participants. The prevalence of cytologically predicted high-grade SIL (HSIL, 17.9%) was lower than histologically diagnosed HSIL (31.7%, P < 0.001). The prevalence of composite-HSIL (detected by either method) was 37.7%. HPV16 prevalence was similar in men with HSIL by cytology (59.3%), HSIL by histology (51.0%), and composite-HSIL (50.0%). HPV16 prevalence was 31.1% in men with composite-atypical squamous cells suggestive of HSIL, to 18.5% in men with composite-low-grade SIL, to 12.1% in men with composite-negative results (Ptrend < 0.001). Significantly more HSIL was detected when a composite cytology-histology endpoint was used. Increasing grade of composite endpoint was associated with increasing HPV16 prevalence. These data suggest that a composite cytology-histology endpoint reflects meaningful disease categories and is likely to be an important biomarker in anal cancer prevention. Cancer Epidemiol Biomarkers Prev; 25(7); 1134-43. ©2016 AACR.

Attitudes towards highly active antiretroviral therapy are associated with sexual risk taking among HIV-infected and uninfected homosexual men.

To determine whether attitudes towards highly active antiretroviral therapy (HAART) are associated with unprotected anal sex among sexually active homosexual men. Cross-sectional study nested within an ongoing prospective cohort study. Multicenter AIDS Cohort Study, from April through September 1999. Five-hundred and forty-seven homosexual men reporting anal sex (218 HIV-negative and 329 HIV-positive) during study interviews in 1999, including a 20-item validated scale on attitudes toward HAART and HIV risk behaviors (e.g., 'Because of HAART, I am less concerned about becoming HIV-infected or infecting someone'), and safer sex fatigue (e.g., 'I am tired of always having safer sex'). Self-reported unprotected receptive anal sex (RAS) and insertive anal sex (IAS) in the prior 6 months. More than 50% of HIV-negative and HIV-positive men who reported having anal sex also reported recent unprotected RAS and/or IAS. HIV-negative men who most agreed that HAART reduced concern about becoming infected were more likely to report unprotected RAS compared to other HIV-negative men [adjusted odds ratio (AOR), 3.31; 95% confidence interval (CI), 1.27-8.62]. Moreover, HIV-positive men with greatest reduced concern due to HAART or safer sex fatigue were more likely to report unprotected IAS (AOR, 6.05; 95% CI, 2.24-16.63 and AOR, 4.57; 95% CI, 1.70-12.24, respectively) compared to other HIV-positive men. Among sexually active homosexual men, lessened concern about HIV transmission due to HAART was strongly associated with sexual risk taking, as was safer sex fatigue among HIV-positive men. Prevention programs should take into account underlying attitudes for unprotected sex in the era of HAART among both HIV-infected and uninfected men.

Analysis of a biallelic polymorphism in the tumor necrosis factor alpha promoter and HIV type 1 disease progression.

The relevance of a TNF-alpha promoter polymorphism, a G-to-A polymorphic sequence at position-308, was examined to test whether variant alleles of TNF-alpha affect susceptibility to infection with HIV-1 and progression to AIDS. Analysis of specimens from cohorts of HIV-1 positive homosexual men demonstrated that 3 of the 32 (9.4%) HIV-1-infected long-term nonprogressors (LTNPs) were homozygous for the uncommon TNF-2 allele compared with 3 of the 196 (1.5%) HIV-1-seronegative blood donors and uninfected homosexual men (p < 0.05). There was no difference in heterozygosity among HIV-1-seropositive or -seronegative groups, although some of the seropositive men heterozygous for the TNF2 genotype were also heterozygous for CCR5delta32. However, no significant association was found between TNF genotypes and time of survival, CD4 slopes, or viral loads when seroincident (n = 109) and seroprevalent cases (n = 442) from the Chicago MACS were analyzed. Functional analysis of lymphocytes from the seronegative group revealed no difference in endogenous or mitogen-induced TNF-alpha production, as well as susceptibility to in vitro HIV-1 infection between different TNF-genotype donors. These data suggest that TNF genotypes do not play a direct role in HIV-1 disease progression; however, they could potentially be part of a multigenic linkage that may be involved in delaying progression to AIDS.

Seroprevalence of human papillomavirus types 6 and 16 capsid antibodies in homosexual men.

Human papillomavirus (HPV) has been implicated in the pathogenesis of anal carcinoma, which is increased in homosexual men. Little is known about the serologic response to HPV in normal or immunosuppressed men; therefore, HIV-infected and -uninfected homosexual men were screened for HPV-6 and -16 capsid antibodies. HIV-infected men had increased HPV DNA detection but did not significantly differ in the prevalence of serum HPV antibodies. HPV-6 DNA detection and the presence of anal warts were significantly correlated with serum antibody overall and in the HIV-infected subgroup. HPV-16 DNA detection was not significantly correlated with serum antibody overall or in either subgroup; however, HIV-infected men with high-grade anal squamous intraepithelial lesions were significantly more likely to have HPV-16 antibodies. HIV-infected men are able to generate an antibody response to HPV, and a lack of serum HPV antibodies cannot explain the increased HPV-associated disease seen in HIV-infected men.

Somatic symptoms and HIV infection: relationship to depressive symptoms and indicators of HIV disease

This study examined the relationship of the somatic symptoms fatigue and insomnia with indicators of both psychiatric disturbance and HIV disease severity. Study participants were 98 asymptomatic HIV-infected and 71 uninfected homosexual men; 82 HIV-infected and 64 uninfected men had 6-month follow-up examinations. Scales from the self-reported Profile of Mood States measured fatigue and dysphoric mood. Major depression diagnosis was determined by the Structured Clinical Interview for DSM-III-R. Selected items from the Hamilton depression and anxiety scales measured insomnia and other symptoms of depression. Performance on a battery of standardized tests determined neuropsychological function ratings. At study entry, complaints of fatigue and insomnia were associated with dysphoric mood, major depression, and other non-HIV-related symptoms of major depression but not with CD4 cell counts or neuropsychological functioning. Increases in levels of fatigue and insomnia over the 6-month follow-up period were associated with increases in non-HIV-related symptoms of depression and in severity of dysphoric mood. Increases in fatigue were also associated with decrements in motor functioning. Otherwise, fatigue or insomnia were not associated with HIV disease progression. These findings suggest that complaints of fatigue and insomnia in otherwise asymptomatic HIV-infected patients are likely to be related to psychological disturbances and possibly major depression, which can be treated. HIV-infected patients who complain of fatigue or insomnia should routinely be assessed for major depression.

Mood disorders in HIV infection: prevalence and risk factors in a nonepicenter of the AIDS epidemic

The authors studied the lifetime, initial cross-sectional, and 6-month follow-up prevalence of mood disorders in asymptomatic HIV-infected and uninfected homosexual men who lived in an area with a low prevalence of HIV. They also determined the relationship between current major depression and potential depression risk factors. Subjects included 98 asymptomatic HIV-infected and 71 uninfected homosexual men. Subjects underwent extensive clinical, psychiatric, neuropsychological, and laboratory evaluations. Similar proportions of HIV-infected and uninfected subjects reported a lifetime (29% and 45%, respectively), an initial current (8% and 3%), and a 6-month follow-up (9% and 11%) history of major depressive disorder. Anxiety disorders were less common, with similar proportions of HIV-infected and uninfected subjects reporting a lifetime (7% and 13%, respectively), an initial current (3% and 7%), and a 6-month follow-up (2% and 5%) history of anxiety disorders. There were no differences in the severity of mood symptoms between HIV-infected and uninfected subjects. Current major depression at initial visit was significantly associated with lifetime history of major depression but not with neuropsychological function or vitamin B12 level. These findings are in agreement with previous studies of areas with a high prevalence of HIV. However, the proportion of subjects with mood disorders is high compared with general population studies. Both HIV-infected and uninfected homosexual men may be at high risk for major depression, especially if they have a past history of depression. Moreover, in the asymptomatic stage of HIV infection, major depression does not appear to be secondary to HIV central nervous system effects or low vitamin B12 levels.

Phenotypic distribution of T cells of patients who have subsequently developed AIDS

In a previous study of asymptomatic homosexual men, we found that CD8 + T-cell levels were higher in homosexual men infected with the human immunodeficiency virus (HIV) than in uninfected homosexual men because of higher numbers of CD8 + T cells that do not express the Leu15 marker, a phenotype associated with cytotoxic function. Among infected men, there was a positive correlation between the number of CD8 +Leu15 − T cells and the number of CD4 + T cells. If CD4 + T-cell levels are taken as a measure of severity of HIV infection and immunodeficiency, these results suggested that higher CD8 +Leu15 − cells may represent a phenotypic profile associated with less severe infection or better control of infection. In the present study, we extend the analysis to include a group of men who progressed to AIDS but were studied well before the onset of AIDS, and we compare results of CD8 subset analyses with results of infected men who have not progressed to AIDS. Phenotypic subsets associated with helper, suppressor, cytotoxic, and natural killer cell function were determined by two-color immunofluorescence. The only phenotypic subset that distinguished men who progressed to AIDS from those who have not was lower numbers of CD4 + T cells in the former group. If CD8 +Leu15 − cell numbers (or other phenotypic subsets examined) reflect effective control of HIV infection, the relationship is not strong enough to be of prognostic or predictive value with respect to outcome of infection.