Prevalence and Genotypic Diversity of Human Papillomavirus Infection Among Male and Female Sex Workers in Thailand.

BACKGROUND: Human papillomavirus (HPV) is associated with cancer. Female sex workers (FSWs) are known to be at risk for HPV, but little is known about male sex workers (MSWs). METHODS: We examined HPV prevalence and associated risk factors in both populations. During 2022, HPV testing using vaginal or penile samples, HIV testing, and interviews were performed among 100 MSWs and 100 FSWs in Chiang Mai, Thailand. RESULTS: The prevalence of all HPV types was 63.5% (66% in MSW, 61% in FSW), HPV-16 prevalence was 14%, HPV-52 was 13%, and HPV-18 was 4%. There was no difference between MSW and FSW for these subtypes. The prevalence of HPV-16 or HPV-18 was 17%, and for HPV-16, HPV-18, or HPV-52, it was 26%. HIV-positive participants had a higher prevalence of all HPV types (94% vs. 60%, P = 0.004), HPV-16 or HPV-18 (39% vs. 15%, P = 0.018), and HPV-16, HPV-18, or HPV-52 (50% vs. 23%, P = 0.017). CONCLUSIONS: We demonstrated an equally high HPV prevalence across the sexes. Further studies are needed to determine if this indicates an equal risk for cancer. Increased HPV awareness, screening, and vaccination should be considered, regardless of gender.

Association of cytologic grade of anal "Pap" smears with viral loads of human papillomavirus types 16, 18, and 52 detected in the same specimens from men who have sex with men.

BACKGROUND: Human papilloma virus (HPV) load has been linked to cellular abnormalities of the uterine cervix, and proposed as predictors of HPV persistence and progression of dysplasia to cervical cancer. However, the association of HPV viral load and anal dysplasia and cancer has not been as thoroughly investigated. OBJECTIVES: To examine the association of the viral loads of high-risk HPV types 16, 18, and 52, with the cytologic severity grading in anal-swab specimens of MSM with and without HIV-1 co-infection. STUDY DESIGN: A cross-sectional study recruited 200 MSM in northern Thailand from July 2012 to January 2013. Real-time qPCR amplified portion of the HPV E6E7 gene, as well as the human ß-globin gene to validate adequacy of the anal specimens and to normalize interpatient viral-load comparisons. Genotyping by linear-array assay identified and distinguished types 16, 18, and 52. RESULTS: HPV-16, and -18 viral loads increased with respect to the abnormality of the cytologic diagnoses (p<0.05 for HPV-16, p<0.01 for HPV-18). HIV-1 positivity was associated with higher HPV-18 viral load (p=0.006). HPV-16 viral loads ≥102.24 copies per 5000 anal cells, and HPV-18 loads ≥103.15, were independently associated with abnormal cytology on logistic regression (p=0.022, p=0.041, respectively). Positive predictive values were 85.2% (23/27) and 80.0% (44/55) for the high viral load of a particular HPV-16 and the combined HPV-16, -18 and -52 types, respectively. CONCLUSIONS: High viral loads of HPV types 16 and 18 appear to be associated with anal cytologic abnormalities. The clinical utility of HPV viral loads to predict risk for anal cancer remains to be determined by a larger prospective cohort with sufficient frequency of high-grade dysplasia.

Cytological Anal Squamous Intraepithelial Lesions Associated with Anal High-Risk Human Papillomavirus Infections among Men Who Have Sex with Men in Northern Thailand.

BACKGROUND: Anal cancer, one of human papillomavirus (HPV) related malignancies, has increased in recent decades, particularly among men who have sex with men (MSM) and HIV-infected (HIV+) persons. We aimed to explore the prevalence of anal squamous intraepithelial lesions (ASIL) using Papanicolau (Pap) screening among MSM in northern Thailand and its associated factors. METHODS: Two hundreds MSM aged ≥18 years reporting receptive anal intercourse in the prior 6 months were recruited from July 2012 through January 2013. Medical history and behavioral data were collected by staff interview and computer-assisted self interview. Anal Pap smear, HPV genotyping, and HIV testing were performed. Two pathologists blinded to HPV and HIV status reported cytologic results by Bethesda classification. RESULTS: Mean age was 27.2 years (range 18-54). Overall, 86 (43.0%) had ASIL: 28 (14.2%) with atypical cells of undetermined significance (ASCUS), 1 (0.5%) with atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H), 56 (28.4%) with low-grade squamous intraepithelial lesion (LSIL), and 1 (0.5%) with high-grade squamous intraepithelial lesion (HSIL). ASIL was associated by univariate analysis (p ≤0.05) with older age, gender identity other than bisexual (i.e., gay men and transgender women), rectal douching, anal symptoms, genital warts, HIV positivity, and high-risk-HPV infection. However, on multiple logistic regression ASIL was associated only with high-risk HPV type (p = 0.002) and HIV infection (p = 0.01). CONCLUSIONS: ASIL is quite common in high-risk MSM in northern Thailand and is associated with high-risk HPV types and HIV infection. Routine anal Pap screening should be considered, given the high frequency of ASIL, particularly in the HIV+. High resolution anoscopy (HRA), not done here, should be to confirm PAP smears whose sensitivity and specificity are quite variable. Timely HPV vaccination should be considered for this population.

Low expression of activation marker CD69 and chemokine receptors CCR5 and CXCR3 on memory T cells after 2009 H1N1 influenza A antigen stimulation in vitro following H1N1 vaccination of HIV-infected individuals.

Unlike well-studied antibody responses to pandemic 2009 H1N1 influenza A virus vaccines in human immunodeficiency virus-infected (HIV+) individuals, less well understood are cell-mediated immune (CMI) responses to this antigen in this susceptible population. We investigated such influenza-specific CMI responses in 61 HIV+ individuals and in 20 HIV-negative (HIV-) healthy controls. Each was vaccinated with a single licensed dose of inactivated, split-virion vaccine comprised of the influenza A/California/7/2009 (H1N1) virus-like strain. Cells collected just prior to vaccination and at 1 and 3 months afterwards were stimulated in vitro with dialyzed vaccine antigen and assayed by flow cytometry for cytokines TNF-α, IFN-γ, IL-2, and IL-10, for degranulation marker CD107a, as well as phenotypes of memory T-cell subpopulations. Comparable increases of cytokine-producing and CD107a-expressing T cells were observed in both HIV+ subjects and healthy HIV-controls. However, by 3 months post-vaccination, in vitro antigen stimulation of peripheral blood mononuclear cells induced greater expansion in controls of both CD4 and CD8 central memory and effector memory T cells, as well as higher expression of the activation marker CD69 and chemokine receptors CCR5 and CXCR3 than in HIV+ subjects. We concluded CD4+ and CD8+ memory T cells produce cytokines at comparable levels in both groups, whereas the expression after in vitro stimulation of molecules critical for cell migration to infection sites are lower in the HIV+ than in comparable controls. Further immunization strategies against influenza are needed to improve the CMI responses in people living with HIV.

High Prevalence and Genotype Diversity of Anal HPV Infection among MSM in Northern Thailand.

BACKGROUND: HPV infection is common and may cause cancer among men who have sex with men (MSM). Anal HPV infection (HPV+) was found in 85% of HIV-positive (HIV+) and 59% of HIV-negative (HIV-) MSM in Bangkok, central Thailand. As little is known about HPV in this group in northern Thailand, we studied MSM subgroups comprised of gay men (GM), bisexual men (BM), and transgender women (TGW). METHODS: From July 2012 through January 2013, 85 (42.5% of 200) GM, 30 (15%) BM, and 85 (42.5%) TGW who practiced receptive anal intercourse were recruited after informed consent, followed by self-assisted computer interview, HIV testing, and anal swabs for HPV genotyping. RESULTS: Of 197 adequate specimens, the overall prevalence of any HPV was 157 (80%). Prevalence was 89% (76/85) in GM, 48% (14/29) in BM, and 81% (67/83) in TGW. The most common high-risk types were HPV16 (27% of 197), HPV58 (23%), and HPV51 (18%). Prevalence of high-risk types was 74% in 85 GM, 35% in 29 BM, and 71% in 83 TGW. Prevalence of any HPV type, or high-risk type, was 100% and 94%, respectively, among 48 HIV+ MSM, 70% and 54% among 120 HIV- MSM. Of the 197 specimens, 36% (70) had HPV types 16 and/or 18 in the bivalent vaccine, compared to 48% (95) with ≥1 of types 16/18/06/11 in the quadrivalent, 56% (111) for 16/18/31/33/45/52/58 in the 7-valent, and 64% (126) for 16/18/31/33/45/52/58/06/11 in the 9-valent. HIV+, GM, and TGW were independently associated with HPV infection. CONCLUSIONS: We found higher rates of both any HPV and high-risk types than previous studies. Among the heretofore unstudied TGW, their equivalent HPV rates were comparable to GM. Current and investigational HPV vaccines could substantially protect GM, BM, and TGW from the serious consequences of HPV infection especially among HIV + MSM.

Correlation of CYP2B6-516G > T Polymorphism with Plasma Efavirenz Concentration and Depression in HIV-Infected Adults in Northern Thailand.

BACKGROUND: Single nucleotide polymorphism of the hepatic cytochrome P450 isoenzyme 2B6 (CYP2B6) gene is a cause of variation in plasma efavirenz (EFV) concentrations. We aimed to determine the allelic distribution of CYP2B6 gene, plasma levels of EFV, the prevalence of clinical depression, and their correlations in northern Thai population. METHODS: This was a cross-sectional study of HIV-infected patients on EFV-containing antiretroviral regimens for ≥48 weeks. A single blood specimen was collected for determination of the mid-dose plasma EFV concentration and CYP2B6- 516G > T polymorphism. The presence and severity of depression were assessed. RESULTS: One hundred patients were enrolled [mean age (±SD) was 41.81±8.44 years, mean CD4 lymphocyte count 462±193 cells/ul]. The genotype CYP2B6-516 guanine/guanine (G/G), guanine/thymidine (G/T), and T/T were found in 49%, 37%, and 14% of patients, respectively. The allele frequency of CYP2B6-516 G to T replacement was 32.5%. The median plasma EFV concentration was 2,616 ng/mL (IQR 1,851-3,742); 79% had EFV plasma concentrations from 1,000 to 4,000 ng/mL. The mean EFV concentrations for those with G/G, G/T and T/T genotypes were 2,082±630, 3,166±1,074, and 11,196±6,265 ng/mL, respectively (p < 0.01). CYP2B6-516G > T polymorphism was the only factor associated with high plasma EFV levels. Nineteen patients had depression; 13 of 18 (72%) with mild and one with major depression had normal plasma EFV level. A weak correlation between plasma EFV concentrations and depression scores was observed (p=0.009, R2=0.059). CONCLUSIONS: The prevalence of CYP2B6-516G > T polymorphism in northern Thai population is high and strongly associated with inter-individual drug levels variation.

Immune response to 2009 H1N1 vaccine in HIV-infected adults in Northern Thailand.

BACKGROUND: In late 2009, the Thai Ministry of Public Health provided two million doses of the monovalent pandemic influenza H1N1 2009 vaccine (Panenza®, Sanofi Pasteur), which was the only vaccine formulation available in Thailand, to persons at risk of more severe manifestations of the disease including HIV infection. Several studies have shown poorer immune responses to the 2009 H1N1 vaccines in HIV-infected individuals. There are limited data in this population in resource-limited countries. RESULTS: At day 28 post-vaccination, seroconversion was found in 32.0% (95%CI 24.5 - 40.2) of the HIV-infected group and 35.0% (95%CI 15.4- 59.2) of the healthy controls (p = 0.79). Seroprotection rate was observed in 33.3% (95%CI 25.8-41.6) and 35.0% (95%CI 15.4-59.2) of the HIV-infected group and the control group, respectively (p = 0.88). Among HIV-infected participants, the strongest factor associated with vaccine response was age 42 y or younger (p = 0.05). METHODS: We evaluated the immunogenicity of a single, 15µg/0.5ml dose of a monovalent, non-adjuvanted 2009 H1N1 vaccine in 150 HIV-infected Thai adults and 20 healthy controls. Immunogenicity was measured by hemagglutination inhibition assay (HI) at baseline and 28 d after vaccination. Seroconversion was defined as 1) pre-vaccination HI titer < 1:10 and post-vaccination HI titer ≥ 1:40, or 2) pre-vaccination HI titer ≥ 1:10 and a minimum of 4-fold rise in post-vaccination HI titer. Seroprotection was defined as a post-vaccination HI titer of ≥ 1:40. CONCLUSIONS: A low seroconversion rate to the 2009 H1N1 vaccine in both study groups, corresponding with data from trials in the region, may suggest that the vaccine used in our study is not very immunogenic. Further studies on different vaccines, dosing, adjuvants, or schedule strategies may be needed to achieve effective immunization in HIV-infected population.