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BACKGROUND: The RV144 phase 3 vaccine trial in Thailand demonstrated that ALVAC-HIV (vCP1521) and AIDSVAX® B/E administration over six months resulted in a 31% efficacy in preventing HIV acquisition. In this trial, we assessed the immunologic impact of an additional vaccine boost to the RV144 regimen at varying intervals between the priming vaccine series and the boost. METHODS: RV306 is a double-blind, placebo-controlled, randomized clinical trial conducted in three clinical sites in Thailand. HIV-uninfected volunteers aged 20–40 randomly received the primary RV144 vaccine series at months 0, 1, 3, and 6, with no additional boost (Group I), additional AIDSVAX® B/E and ALVAC-HIV (vcp1521) at month 12 (Group II), AIDSVAX® B/E alone at month 12 (Group III), AIDSVAX® B/E and ALVAC-HIV at month 15 or 18 (Groups IVa or IVb), or placebo and were followed for 24 months. A randomization schedule was centrally generated with fixed sized strata for RIHES Chiang Mai (n=60) and combined Bangkok clinics (n=300). Primary outcomes were to assess the safety and tolerability of these vaccination regimens and characterize and compare cellular and humoral immune responses between the RV144 series alone and late boosts at different timepoints. Safety and tolerability outcomes were assessed by evaluating local and systemic reactogenicity and adverse events in all participants. Primary immunogenicity outcomes were evaluated by comparing peak humoral responses (HIV-specific IgG and IgA ELISA) and cellular responses (HIV-specific intracellular cytokine staining and polyfunctionality) two weeks post final vaccination among per-protocol participants who completed all vaccinations. This trial is registered at (ClinicalTrials.gov (NCT01931358); clinical follow up is now complete. FINDINGS: Between 28 October 2013 and 29 April 2014, 367 participants were enrolled, of whom 27 were assigned active vaccination in Group I, 102 in Group II, 101 in Group III, 52 in Group IVa, 51 in Group IVb, and 34 combined placebo across all groups. Late boosting did not induce vaccine-related serious adverse events. There were no significant differences in the occurrence or severity of local or systemic reactogenicity across active groups. Groups with late boosts (Groups II, III, IVa, and IVb) had increased peak plasma IgG binding antibody levels against gp70 V1V2 relative to Group I vaccine recipients with no late boost (gp70V1V2 92TH023 adjusted p < 0·02 for each; gp70V1V2 Case A2 adjusted p month 15 (Group IVa) > month 12 (Groups II+III) > no late boost (Group I). Groups with late boosts had increased both functionality and polyfunctionality scores relative to vaccine recipients with no late boost (all adjusted p < 0·05, except for polyfunctionality score in Group I vs in Group IVb p < 0·01). INTERPRETATION: Taken together, these results suggest that additional boosting of the RV144 regimen with longer intervals between the primary vaccination series and late boost improved immune responses and may improve the efficacy of preventing HIV acquisition. FUNDING: US National Institute of Allergy and Infectious Diseases (NIAID) and U.S. Department of the Army.

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 β-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 p p =0.006). HPV-16 viral loads ≥10 2.24 copies per 5000 anal cells, and HPV-18 loads ≥10 3.15 , 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.

HIV-infected adults have increased risk of several individual micronutrient deficiencies. However, the prevalence and risk factors of concurrent and multiple micronutrient deficiencies and whether micronutrient concentrations change after antiretroviral therapy (ART) initiation have not been well described. The objective of this study was to determine the prevalence and risk factors of individual, concurrent and multiple micronutrient deficiencies among ART-naïve HIV-infected adults from nine countries and assess change in micronutrient status 48 weeks post-ART initiation.A random sub-cohort (n = 270) stratified by country was selected from the multinational PEARLS clinical trial (n = 1571 ART-naïve, HIV-infected adults). We measured serum concentrations of vitamins A, D (25-hydroxyvitamin), E, carotenoids and selenium pre-ART and 48 weeks post-ART initiation, and measured vitamins B6, B12, ferritin and soluble transferrin receptor at baseline only. Prevalence of single micronutrient deficiencies, concurrent (2 coexisting) or conditional (a deficiency in one micronutrient given a deficiency in another) and multiple (≥3) were determined using defined serum concentration cutoffs. We assessed mean changes in micronutrient concentrations from pre-ART to week 48 post-ART initiation using multivariable random effects models.Of 270 participants, 13.9%, 29.2%, 24.5% and 32.4% had 0, 1, 2 and multiple deficiencies, respectively. Pre-ART prevalence was the highest for single deficiencies of selenium (53.2%), vitamin D (42.4%), and B6 (37.3%) with 12.1% having concurrent deficiencies of all three micronutrients. Deficiency prevalence varied widely by country. 48 weeks post-ART initiation, mean vitamin A concentration increased (p 0.001) corresponding to a 9% decrease in deficiency. Mean concentrations also increased for other micronutrients assessed 48 weeks post-ART (p 0.001) but with minimal change in deficiency status.Single and multiple micronutrient deficiencies are common among HIV-infected adults pre-ART initiation but vary between countries. Importantly, despite increases in micronutrient concentrations, prevalence of individual deficiencies remains largely unchanged after 48 weeks on ART. Our results suggest that ART alone is not sufficient to improve micronutrient deficiency.

Summary Background Antiretroviral therapy (ART) management is challenging for individuals in resource-limited settings presenting for third-line treatment because of complex resistance patterns, partly due to reduced access to viral load monitoring. We aimed to evaluate use of newer antiretroviral drugs and contemporary management approaches, including population-based sequencing, to select appropriate antiretrovirals, plasma viral load monitoring, and interventions to improve adherence in individuals presenting with second-line viral failure. Methods A5288 was a phase 4, third-line ART strategy study done at 19 urban sites in ten countries that enrolled adult participants with confirmed plasma HIV-1 RNA (viral load) of 1000 copies per mL or more after more than 24 weeks of protease inhibitor-based second-line ART. The primary objective was to use antiretrovirals (raltegravir, etravirine, and ritonavir-boosted darunavir) and diagnostic monitoring technologies, including viral load, genotyping, and adherence support to achieve viral load suppression (defined as ≤200 copies per mL) in 65% or more of participants. ART history and real-time drug resistance genotypes were used to assign participants to one of four cohorts: cohort A (no lopinavir resistance) stayed on second-line ART and cohorts B (B1, best available nucleoside reverse transcriptase inhibitors [NRTIs] plus ritonavir-boosted darunavir plus raltegravir; B2, ritonavir-boosted darunavir plus raltegravir plus etravirine; B3, ritonavir-boosted darunavir, raltegravir, and either tenofovir plus emtricitabine or tenofovir plus lamivudine), C (ritonavir-boosted darunavir plus raltegravir plus tenofovir-emtricitabine or tenofovir plus lamivudine), and D (best available NRTIs plus ritonavir-boosted darunavir plus raltegravir) were defined by increasing levels of resistance and received appropriate regimens, including new antiretrovirals. Participants in Cohort B without detectable hepatitis B surface antigen were assigned by blocked randomisation to cohorts B1 and B2, and those with detectable hepatitis B surface antigen were assigned to cohort B3. The trial is registered with ClinicalTrials.gov , number NCT01641367 . Findings From Jan 10, 2013, to Sept 10, 2015, 545 participants were enrolled. 287 (53%) were assigned to cohort A, 74 (14%) to B1, 72 (13%) to B2, eight (1%) to B3, 70 (13%) to C, and 34 (6%) to D. Overall, 349 (64%, 95% CI 60–68) participants achieved viral suppression at week 48, with proportions varying from 125 (44%) of 287 in cohort A to 65 (88%) of 74 in cohort B1, 63 (88%) of 72 in B2, eight (100%) of eight in B3, 63 (90%) of 70 in C, and 25 (74%) of 34 in D. Participants in cohort A remained on their second-line protease inhibitor, and had the most participants with grade 3 or higher adverse events (147 [51%]). Interpretation Targeted real-time genotyping to select third-line ART can appropriately allocate more costly antiretrovirals to those with greater levels of HIV drug resistance. Funding National Institutes of Health.

A case-cohort analysis of human immunodeficiency virus (HIV)–infected individuals receiving antiretroviral therapy (ART) was performed within a multicountry randomized trial (PEARLS) to assess the prevalence of persistently elevated C-reactive protein (CRP) levels, based on serial measurements of CRP levels, and their association with HIV clinical failure. A persistently elevated CRP level in plasma (defined as ≥ 5 mg/L at both baseline and 24 weeks after ART initiation) was observed in 50 of 205 individuals (24%). A persistently elevated CRP level but not an elevated CRP level only at a single time point was independently associated with increased clinical failure, compared with a persistently low CRP level, despite achievement of virologic suppression. Serial monitoring of CRP levels could identify individuals who are at highest risk of HIV progression and may benefit from future adjunct antiinflammatory therapies.

Mark W. Tenforde, MD, MPH,* Ashish Yadav, MBBS, MD, MPH,† David W. Dowdy, MD, PhD, Nikhil Gupte, PhD,§ Rupak Shivakoti, PhD, MSPH,§ Wei-Teng Yang, MD, MPH,k Noluthando Mwelase, MBChB, Cecilia Kanyama, MD,# Sandy Pillay, MBChB,** Wadzanai Samaneka, MBChB, MSc,†† Breno Santos, MD,‡‡ Selvamuthu Poongulali, MBBS,§§ Srikanth Tripathy, MBBS,kk Cynthia Riviere, MD, Sima Berendes, MD, MPH,##*** Javier R. Lama, MD, MPH,††† Sandra W. Cardoso, MD,‡‡‡ Patcharaphan Sugandhavesa, MD,§§§ Rarul Christian, DrPH, MSc,† Richard D. Semba, MD, MPH,kkk Thomas B. Campbell, MD, and Amita Gupta, MD, MHS,†§ the NWCS319 and ACTG 5175 study team From the *Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA; Departments of †International Health; ‡Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; §Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; kDepartment of Medicine, Bridgeport Hospital, Yale New Haven Health, Bridgeport, CT; Department of Medicine, University of Witwatersrand, Johannesburg, South Africa; #UNC Lilongwe, Lilongwe, Malawi; **Durban International Clinical Research Site, Durban University of Technology, Durban, South Africa; ††University of Zimbabwe Clinical Research Centre, Harare, Zimbabwe; ‡‡Hospital Nossa Senhora de Conceicao, Porto Alegre, Brazil; §§YR Gaitonde Centre for AIDS Research and Education, Chennai, India; kkNational AIDS Research Institute, Pune, India; Les Centres GHESKIO, Port-Au-Prince, Haiti; ##Malawi College of Medicine, Johns Hopkins University Research Project, Blantyre, Malawi; ***Liverpool School of Tropical Medicine, Liverpool, United Kingdom; †††Asociacion Civil Impacta Salud y Educacion, Lima, Peru; ‡‡‡STD/AIDS Clinical Research Laboratory, Instituto de Pesquisa Clinica Evandro Chagas, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil; §§§Research Institute for Health Sciences, Chiang Mai, Thailand; kkkDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD; and Division of Infectious Diseases, Department of Medicine, University of Colorado School of Medicine, Aurora, CO.

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Background: Women progress to death at the same rate as men despite lower plasma HIV RNA (viral load). We investigated sexspecific differences in immune activation and inflammation as a potential explanation. Methods: Inflammatory and immune activation markers [interferon-γ, tumor necrosis factor (TNF) α, IL-6, IL-18, IFN-γ- induced protein 10, C-reactive protein (CRP), lipopolysaccharide, and sCD14] were measured at weeks 0, 24, and 48 after combination antiretroviral therapy (cART) in a random subcohort (n = 215) who achieved virologic suppression in ACTG A5175 (Prospective Evaluation of Antiretrovirals in Resource-Limited Settings). Association between sex and changes in markers postcART was examined using random effects models. Average marker differences and 95% confidence intervals were estimated using multivariable models. Results: At baseline, women had lower median log10viral load (4.93 vs 5.18 copies per milliliter, P = 0.01), CRP (2.32 vs 4.62 mg/L, P = 0.01), detectable lipopolysaccharide (39% vs 55%, P = 0.04), and sCD14 (1.9 vs 2.3 μg/mL, P = 0.06) vs men. By week 48, women had higher interferon -γ (22.4 vs 14.9 pg/mL, P = 0.05), TNF-α (11.5 vs 9.5 pg/mL, P = 0.02), and CD4 (373 vs 323 cells per cubic millimeter, P = 0.02). In multivariate analysis, women had greater increases in CD4 and TNF-α but less of a decrease in CRP and sCD14 compared with men. Conclusions: With cART-induced viral suppression, women have less reduction in key markers of inflammation and immune activation compared with men. Future studies should investigate the impact of these sex-specific differences on morbidity and mortality.

© 2016 The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. Background. Both wasting and obesity are associated with inflammation, but the extent to which body weight changes influence inflammation during human immunodeficiency virus infection is unknown. Methods. Among a random virologically suppressed participants of the Prospective Evaluation of Antiretrovirals in Resource-Limited Settings trial, inflammatory markers were measured at weeks 0, 24, and 48 after antiretroviral therapy (ART) initiation. Associations between both baseline and change in body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared) and changes in inflammation markers were assessed using random effects models. Results. Of 246 participants, 27% were overweight/obese (BMI, ≥ 25), and 8% were underweight (BMI < 18.5) at baseline. After 48 weeks, 37% were overweight/obese, and 3% were underweight. While level of many inflammatory markers decreased 48 weeks after ART initiation in the overall group, the decrease in C-reactive protein (CRP) level was smaller in overweight/obese participants (P =. 01), and the decreases in both CRP (P =. 01) and interleukin 18 (P =. 02) levels were smaller in underweight participants. Each 1-unit gain in BMI among overweight/obese participants was associated with a 0.02-log10increase in soluble CD14 level (P =. 05), while each 1-unit BMI gain among underweight participants was associated with a 9.32-mg/L decrease in CRP level (P =. 001). Conclusions. Being either overweight or underweight at ART initiation was associated with heightened systemic inflammation. While weight gain among overweight/obese persons predicted increased inflammation, weight gain among underweight persons predicted reduced inflammation.

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 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.

Background. We assessed immune activation after antiretroviral therapy (ART) initiation to understand clinical failure in diverse settings. Methods. We performed a case-control study in ACTG Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS). Cases were defined as incident World Health Organization Stage 3 or 4 human immunodeficiency virus (HIV) disease or death, analyzed from ART weeks 24 (ART24) to 96. Controls were randomly selected. Interleukin (IL)-6, interferon (IFN)-γ-inducible protein-10, IL-18, tumor necrosis factor-α, IFN-γ, and soluble CD14 (sCD14) were measured pre-ART and at ART24 in plasma. Continued elevation was defined by thresholds set by highest pre-ART quartiles (>Q3). Incident risk ratios (IRRs) for clinical progression were estimated by Poisson regression, adjusting for age, sex, treatment, country, time-updated CD4+ T-cell count, HIV ribonucleic acid (RNA), and prevalent tuberculosis. Results. Among 99 cases and 234 controls, median baseline CD4+ T-cell count was 181 cells/µL, and HIV RNA was 5.05 log10 cp/mL. Clinical failure was independently associated with continued elevations of IL-18 (IRR, 3.03; 95% confidence interval [CI], 1.27–7.20), sCD14 (IRR, 2.17; 95% CI, 1.02–4.62), and IFN-γ (IRR, 0.08; 95% CI, 0.01–0.61). Among 276 of 333 (83%) who were virologically suppressed at ART24, IFN-γ was associated with protection from failure, but the association with sCD14 was attenuated. Conclusions. Continued IL-18 and sCD14 elevations were associated with clinical ART failure. Interferon-γ levels may reflect preserved immune function.

BACKGROUND Anemia is a known risk factor for clinical failure following antiretroviral therapy (ART). Notably, anemia and inflammation are interrelated, and recent studies have associated elevated C-reactive protein (CRP), an inflammation marker, with adverse human immunodeficiency virus (HIV) treatment outcomes, yet their joint effect is not known. The objective of this study was to assess prevalence and risk factors of anemia in HIV infection and to determine whether anemia and elevated CRP jointly predict clinical failure post-ART. METHODS A case-cohort study (N = 470 [236 cases, 234 controls]) was nested within a multinational randomized trial of ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings [PEARLS]). Cases were incident World Health Organization stage 3, 4, or death by 96 weeks of ART treatment (clinical failure). Multivariable logistic regression was used to determine risk factors for pre-ART (baseline) anemia (females: hemoglobin

A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (&lt, 85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28–99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86–95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50, 95% confidence intervals (CI): 1.30–9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium.

STUDY BACKGROUND\ud Vitamin D has wide-ranging effects on the immune system, and studies suggest that low serum vitamin D levels are associated with worse clinical outcomes in HIV. Recent studies have identified an interaction between antiretrovirals used to treat HIV and reduced serum vitamin D levels, but these studies have been done in North American and European populations.\ud \ud METHODS\ud Using a prospective cohort study design nested in a multinational clinical trial, we examined the effect of three combination antiretroviral (cART) regimens on serum vitamin D levels in 270 cART-naïve, HIV-infected adults in nine diverse countries, (Brazil, Haiti, Peru, Thailand, India, Malawi, South Africa, Zimbabwe and the United States). We evaluated the change between baseline serum vitamin D levels and vitamin D levels 24 and 48 weeks after cART initiation.\ud \ud RESULTS\ud Serum vitamin D levels decreased significantly from baseline to 24 weeks among those randomized to efavirenz/lamivudine/zidovudine (mean change: -7.94 [95% Confidence Interval (CI) -10.42, -5.54] ng/ml) and efavirenz/emtricitabine/tenofovir-DF (mean change: -6.66 [95% CI -9.40, -3.92] ng/ml) when compared to those randomized to atazanavir/emtricitabine/didanosine-EC (mean change: -2.29 [95% CI -4.83, 0.25] ng/ml). Vitamin D levels did not change significantly between week 24 and 48. Other factors that significantly affected serum vitamin D change included country (p

Selenium status, with important roles in oxidative stress and immunity, has a non-linear U-shaped association with all-cause mortality in US populations; in HIV-infected persons, low selenium is associated with increased viral load. Factors associated with selenium deficiency and whether selenium is independently associated with HIV ART outcomes in HIV-infected persons is unknown. We performed a multi-country case-cohort where cases were HIV-1 infected adults with either clinical failure (incident WHO stage 3, 4 or death by 96 weeks) or virologic failure (HIV RNA levels 蠅 1000 copies/mL for 2 successive visits at 蠅16 weeks). Median baseline selenium levels were 82.04 µg/L (IQR: 57.28 - 99.89) and selenium deficiency prevalence was 53% varying widely by country from 0% (US) to 100% (Zimbabwe). Independent risk factors for baseline selenium deficiency (

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.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).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 titer1:10 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.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.

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., PLOS ONE, 10(5), e0124499; 2015