Cervical cytological abnormalities and HPV infection in perinatally HIV-infected adolescents.

BACKGROUND: Behaviourally HIV-infected adolescent females are at higher risk for abnormal cervical cytology and HPV infection compared to those who are uninfected, but data on perinatally HIV-infected adolescent females are lacking. METHODS: Cervical cytology, HPV infection and E6/E7 mRNA were assessed in sexually active 12-24-year-old adolescent females: perinatally HIV-infected (group 1, n = 40), behaviourally HIV-infected (group 2, n = 10), and HIV-uninfected (group 3, n = 10). RESULTS: Median age was lower in group 1 (18 years) than in groups 2 (24 years) and 3 (20.5 years) (P < 0.001), and median time since sexual debut was shorter: 2 vs 5 vs 4 years (P < 0.001). More trial participants in group 1 than group 2 were on antiretrovirals (90% vs 70%; P <0.001). Abnormal cervical cytology (atypical squamous cells of undetermined significance and higher) was observed in 30% (group 1), 40% (group 2) and 30% (group 3) (P = 0.92), whereas high-risk HPV infection was observed in 45%, 45% and 40%, respectively (P = 1.00). Positive E6/E7 mRNA was found in 28% of group 1, but not in other groups. High-risk HPV infection predicted abnormal cytology in all groups [OR 6.77, 95% confidence interval (CI) 1.99-23.0; P = 0.001). Additionally, plasma HIV RNA ≥50 copies/mL (OR 13.3, 95% CI 1.16-153.06; P = 0.04) predicted abnormal cytology in HIV-infected adolescent females. CONCLUSIONS: Despite the younger age and shorter time since sexual debut, cervical cytological abnormalities and HPV infection were as common in perinatally HIV-infected as in behaviourally infected and uninfected adolescents. HPV vaccination, pre-cancer screening and antiretroviral treatment in HIV-infected female adolescents should be implemented to minimise the risk of cervical cancer.

Determinants of epidermal nerve fibre density in antiretroviral-naïve HIV-infected individuals.

OBJECTIVES: Distal leg epidermal nerve fibre density (ENFD) is a validated predictor of small unmyelinated nerve fibre damage and neuropathy risk in HIV infection. As pre-existing damage may increase the risk of neuropathy following antiretroviral (ARV) therapy, particularly when the regimen contains stavudine (d4T), we assessed the relationship between ENFD and various parameters including mitochondrial factors in HIV-infected Thai individuals naïve to ARV therapy. METHODS: Distal leg and proximal thigh ENFDs were quantified in HIV-infected Thai individuals without neuropathy prior to randomization to a HIV clinical trial that focused on mitochondrial toxicity issues. We assessed their association with various clinical and immunovirological parameters as well as with peripheral blood mononuclear cell (PBMC) mitochondrial (mt) DNA copies/cell, oxidative phosphorylation (OXPHOS) complex I (CI) and complex IV (CIV) enzyme activities, and mt 8-oxo-deoxyguanine (8-oxo-dG) break frequencies. RESULTS: In 132 subjects, the median (interquartile range) ENFD (fibres/mm) values were 21.0 (16.2-26.6) for the distal leg and 31.7 (26.2-40.0) for the proximal thigh. By linear regression, lower CD4 count (P < 0.01), older age (P < 0.01), increased body mass index (BMI) (P = 0.04), increased height (P = 0.02), and higher PBMC OXPHOS activity as measured by CIV activity (P = 0.02) were associated with lower distal leg ENFD. CONCLUSIONS: Older age, increased height, higher BMI, poorer immunological status and higher PBMC OXPHOS activity are associated with lower distal leg ENFD in HIV-infected subjects free of neuropathy prior to initiation of first-time ARV therapy.

Anal squamous intraepithelial lesions among HIV positive and HIV negative men who have sex with men in Thailand.

OBJECTIVES: To evaluate the prevalence and risk factors of anal squamous intraepithelial lesions (ASIL), the putative anal cancer precursor, in Asian HIV positive and HIV negative men who have sex with men (MSM). METHODS: Men who underwent anal Pap smear reported clinical, sociodemographic and behavioural information collected through questionnaire and interview between January 2007 and April 2008. Chi(2) and logistic regression were used to evaluate ASIL prevalence and risk factors among HIV positive and HIV negative MSM. RESULTS: Of the 174 MSM (mean age 32.1 years), 118 (67.8%) were HIV positive. Overall, 27% had abnormal anal cytology: 13.2% had atypical squamous cells of undetermined significance (ASC-US), 11.5% had low-grade squamous intraepithelial lesion (LSIL) and 2.3% had high-grade squamous intraepithelial lesion (HSIL). Prevalence of ASIL was higher among HIV positive than HIV negative MSM (33.9% vs 12.5%; p = 0.003). Among HIV positive MSM, 16.1% had ASC-US, 14.4% had LSIL and 3.4% had HSIL and 7.1%, 5.4% and 0% in HIV negative MSM, respectively. Anal condyloma was detected in 22% of HIV positive and 16.1% (9/56) of HIV negative MSM (p = 0.5). In HIV positive MSM, anal condyloma (OR 3.42, 95% CI 1.29 to 9.04; p = 0.01) was a significant risk factor for ASIL. Highly active antiretroviral therapy use and CD4+ T cell count were not associated with ASIL. CONCLUSIONS: One-third of HIV positive and 12.5% of HIV negative MSM had ASIL. Thus, as greater numbers of HIV positive MSM live longer due to increasing access to HAART worldwide, effective strategies to screen and manage anal precancerous lesions are needed.