BackgroundFourth generation (4thG) immunoassay (IA) is becoming the standard HIV screening method but was not available when the Fiebig acute HIV infection (AHI) staging system was proposed. Here we evaluated AHI staging based on a 4thG IA (4thG staging).FindingsScreening for AHI was performed in real-time by pooled nucleic acid testing (NAT, n=48,828 samples) and sequential enzyme immunoassay (EIA, n=3,939 samples) identifying 63 subjects with non-reactive 2nd generation EIA (Fiebig stages I (n=25), II (n=7), III (n=29), IV (n=2)). The majority of samples tested (n=53) were subtype CRF_01AE (77%). NAT+ subjects were re-staged into three 4thG stages: stage 1 (n=20; 4th gen EIA-, 3rd gen EIA-), stage 2 (n=12; 4th gen EIA+, 3rd gen EIA-), stage 3 (n=31; 4th gen EIA+, 3rd gen EIA+, Western blot-/indeterminate). 4thG staging distinguishes groups of AHI subjects by time since presumed HIV exposure, pattern of CD8+ T, B and natural killer cell absolute numbers, and HIV RNA and DNA levels. This staging system further stratified Fiebig I subjects: 18 subjects in 4thG stage 1 had lower HIV RNA and DNA levels than 7 subjects in 4thG stage 2.ConclusionsUsing 4th generation IA as part of AHI staging distinguishes groups of patients by time since exposure to HIV, lymphocyte numbers and HIV viral burden. It identifies two groups of Fiebig stage I subjects who display different levels of HIV RNA and DNA, which may have implication for HIV cure. 4th generation IA should be incorporated into AHI staging systems.

Background HIV-positive men who have sex with men (MSM) have a higher prevalence of anal human papillomavirus (HPV) infection and anal cancer incidence than HIV-negative MSM. High-risk HPV persistence is an important risk factor for the development of anal cancer. Methods A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled from the Thai Red Cross AIDS Research Centre in Bangkok, Thailand, and followed for 12 months. Anal sample collection for HPV genotyping was performed at every visit. HPV prevalence, incidence, clearance and persistence were calculated. A logistic regression model was used to study factors associated with high-risk HPV persistence. Results The prevalence of any anal HPV infection was 85% in HIV-positive and 58.5% in HIV-negative MSM (p<0.0001). The prevalence of high-risk HPV infection was 57.5% in HIV-positive and 36.6% in HIV-negative MSM (p=0.001). HPV 16 was the most common high-risk HPV type. HIV-positive MSM had a higher prevalence (22.5% vs. 9.8%, p=0.008) and persistence (16.7% vs. 1.3%, p<0.001) of HPV 16 than HIV-negative MSM, and a trend for higher incidence (16.1 vs. 6.1 episodes/1000 person-months, incidence rate ratio 2.6, p=0.058). HIV infection (OR 4.45, 95% CI 2.11–9.4, p<0.001) and smoking in HIV-positive MSM (OR 2.3, 95% CI 1.17–4.5, p=0.015) were independently associated with high-risk HPV persistence in multivariate models. Conclusions In addition to targeting HIV-positive MSM who are at higher risk for anal high-risk HPV persistence, anal cancer prevention programs should also integrate behavioral interventions such as smoking cessation to modify risk for high-risk HPV persistence.

Introduction Concerns over potential drug‐drug interactions (DDI) between feminizing hormone therapy (FHT) and pre‐exposure prophylaxis (PrEP) have hampered uptake and adherence of PrEP among transgender women (TGW). To determine DDI between FHT and PrEP, we measured the pharmacokinetic (PK) parameters of blood plasma estradiol (E2) and tenofovir (TFV) in Thai TGW. Methods Twenty TGW who never underwent orchiectomy and had not received injectable FHT within six months were enrolled between January and March 2018. FHT (E2 valerate and cyproterone acetate) were prescribed to participants at baseline until week 5, and then from week 8 until the end of study. Daily PrEP (tenofovir disoproxil fumarate/emtricitabine) was initiated at week 3 and continued without interruption. Intensive E2 PK parameters and testosterone concentration at 24 hours (C24) were measured at weeks 3 (without PrEP) and 5 (with PrEP), and intensive TFV PK parameters were measured at weeks 5 (with FHT) and 8 (without FHT). Results Median (interquartile range) age, body mass index, and creatinine clearance were 21.5 (21–26) years, 20.6 (19.0‐22.4) kg/m2, and 116 (101‐126.5) mL/min, respectively. The geometric mean (%CV) of area under curve from time zero to 24 hours (AUC0‐24), maximum concentration (Cmax), and C24 of E2 at weeks 3 and 5 were 775.13 (26.2) pg h/mL, 51.47 (26.9) pg/mL, and 15.15 (42.0) pg/mL; and 782.84 (39.6), 55.76 (32.9), and 14.32 (67.4), respectively. The geometric mean (%CV) of TFV AUC0‐24, Cmax, and C24 at weeks 5 and 8 were 2242.1 (26.5) ng h/mL, 353.9 (34.0) ng/mL, and 40.9 (31.4) ng/mL; and 2530.2 (31.3), 311.4 (30.0), and 49.8 (29.6), respectively. The geometric mean of TFV AUC0‐24 and C24 at week 5 were significantly less than that at week 8 by 12% (p = 0.03) and 18% (p < 0.001), respectively. There were no significant changes in E2 PK parameters and median C24 of bioavailable testosterone between week 3 and week 5. Conclusions Our study demonstrated lower blood plasma TFV exposure in the presence of FHT, suggesting that FHT may potentially affect PrEP efficacy among TGW; but E2 exposure was not affected by PrEP. Further studies are warranted to determine whether these reductions in TFV are clinically significant. Clinical Trial Number: NCT03620734.

BackgroundMen who have sex with men (MSM) are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL) is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV) infection and HPV-mediated cell transformation to detect and predict HSIL among HIV-positive and HIV-negative MSM.Methodology/Principal FindingsA total of 123 HIV-positive and 123 HIV-negative MSM were enrolled and followed for 12 months. High-resolution anoscopy (HRA) with biopsies were performed at every visit along with anal sample collection for cytology, high-risk HPV DNA genotyping, HPV E6/E7 mRNA, and p16 immunocytochemistry. Performance characteristics and area under the receiver operator characteristics curve were calculated for these biomarkers at baseline, and Cox regression compared the usefulness of these biomarkers in predicting incident HSIL. High-risk HPV DNA, E6/E7 mRNA, and p16 immunocytochemistry each identified 43–46% of MSM whose baseline test positivity would trigger HRA referral. E6/E7 mRNA had the highest sensitivity (64.7%) and correctly classified the highest number of prevalent HSIL cases. With the exception of p16 immunochemistry, most tests showed significant increases in sensitivity but decreases specificity versus anal cytology, while the overall number of correctly classified cases was not significantly different. Baseline or persistent type 16 and/or 18 HPV DNA was the only test significantly predicting incident histologic HSIL within 12 months in models adjusted for HIV status and low-grade squamous intraepithelial lesions at baseline.Conclusions/SignificanceCountries with a high HIV prevalence among MSM and limited HRA resources may consider using biomarkers to identify individuals at high risk of HSIL. E6/E7 mRNA had the highest sensitivity for prevalent HSIL detection regardless of HIV status, whereas type 16 and/or 18 HPV DNA performed best in predicting development of incident HSIL within 12 months.

Introduction Online, supervised, HIV self‐testing has potential to reach men who have sex with men (MSM) and transgender women (TGW) who never tested before and who had high HIV‐positive yield. We studied linkages to HIV confirmatory test and antiretroviral therapy (ART) initiation among Thai MSM and TGW who chose online and/or offline platforms for HIV testing and factors associated with unsuccessful linkages. Methods MSM and TGW were enrolled from Bangkok Metropolitan Region and Pattaya during December 2015 to June 2017 and followed for 12 months. Participants could choose between: 1) offline HIV counselling and testing (Offline group), 2) online pre‐test counselling and offline HIV testing (Mixed group) and 3) online counselling and online, supervised, HIV self‐testing (Online group). Sociodemographic data, risk behaviour and social network use characteristics were collected by self‐administered questionnaires. Linkages to HIV confirmatory testing and/or ART initiation were collected from participants who tested reactive/positive at baseline and during study follow‐up. Modified Poisson regression models identified covariates for poor retention and unsuccessful ART initiation. Results Of 465 MSM and 99 TGW, 200 self‐selected the Offline group, 156 the Mixed group and 208 the Online group. The Online group demonstrated highest HIV prevalence (15.0% vs. 13.0% vs. 3.4%) and high HIV incidence (5.1 vs. 8.3 vs. 3.2 per 100 person‐years), compared to the Offline and Mixed groups. Among 60 baseline HIV positive and 18 seroconversion participants, successful ART initiation in the Online group (52.8%) was lower than the Offline (84.8%) and Mixed groups (77.8%). Factors associated with unsuccessful ART initiation included choosing to be in the Online group (aRR 3.94, 95% CI 1.07 to 14.52), <17 years old at first sex (aRR 3.02, 95% CI 1.15 to 7.92), amphetamine‐type stimulants use in the past six months (aRR 3.6, 95% CI 1.22 to 10.64) and no/single sex partner (aRR 3.84, 95%CI 1.36 to 10.83) in the past six months. Conclusions Online, supervised, HIV self‐testing allowed more MSM and TGW to know their HIV status. However, linkages to confirmatory test and ART initiation once tested HIV‐reactive are key challenges. Alternative options to bring HIV test confirmation, prevention and ART services to these individuals after HIV self‐testing are needed.