Uptake of oral fluid-based HIV self-testing among men who have sex with men and transgender women in Thailand.

BACKGROUND: Suboptimal uptake of HIV testing remains a primary bottleneck to HIV prevention and treatment for men who have sex with men (MSM) and transgender women (TGW) in Thailand. The World Health Organization has recommended HIV self-testing (HIVST) as an additional strategic HIV service. However, HIVST has not been fully endorsed and implemented in many countries in Southeast Asia. The aim of this study was to assess the uptake of oral fluid-based HIVST in MSM and TGW populations in Thailand. METHODS: During 2017 and 2018, we conducted a cross-sectional study using convenience sampling to enroll 2,524 participants from three major urban areas. Participants were recruited during outreach and online activities and were offered unassisted or assisted HIVST, or referral to HIV testing services. A descriptive analysis was performed for summarizing data. RESULTS: A total of 2,502 participants (1,422 MSM and 1,082 TGW) were included in the analysis with about one-third (36.1%) of them being first-time testers. Among all participants enrolled in the study, a total of 2,486 participants (99.3%) selected HIVST versus referral to HIV testing services. Of those who selected HIVST, 2,095 (84.3%) opted for assisted HIVST while the rest opted for unassisted HIVST: 1,148 of 1,411 MSM (81.4%) and 947 of 1,075 TGW (88.1%) selected assisted HIVST. While no serious adverse events were reported during the study, we found that among 179 participants who needed a confirmatory test and were referred to HIV testing services, 108 (60.3.4%) accessed these later services. CONCLUSIONS: This study demonstrated a high uptake of oral fluid-based HIVST among MSM and TGW populations in Thailand and that HIVST could be scaled up through the national epidemic control program. However, a better understanding of HIV testing-seeking behavior and innovative follow-up solutions are needed to improve and monitor linkages to services for people who undertake HIVST.

Central Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials: An Observational Study in Acutely Treated People Living With Human Immunodeficiency Virus.

BACKGROUND: The central nervous system (CNS) is a likely reservoir of human immunodeficiency virus (HIV), vulnerable to viral rebound, inflammation, and clinical changes upon stopping antiretroviral therapy (ART). It is critical to evaluate the CNS safety of studies using analytic treatment interruption (ATI) to assess HIV remission. METHODS: Thirty participants who started ART during acute HIV infection underwent CNS assessments across 4 ATI remission trials. ART resumption occurred with plasma viral load >1000 copies/mL. CNS measures included paired pre- vs post-ATI measures of mood, cognitive performance, and neurologic examination, with elective cerebrospinal fluid (CSF) sampling, brain diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). RESULTS: Median participant age was 30 years old and 29/30 were male. Participants' median time on ART before ATI was 3 years, and ATI lasted a median of 35 days. Post-ATI, there were no differences in median mood scores or neurologic findings and cognitive performance improved modestly. During ATI, a low level of CSF HIV-1 RNA was detectable in 6 of 20 participants with plasma viremia, with no group changes in CSF immune activation markers or brain DTI measures. Mild worsening was identified in post-ATI basal ganglia total choline MRS, suggesting an alteration in neuronal membranes. CONCLUSION: No adverse CNS effects were observed with brief, closely monitored ATI in participants with acutely treated HIV, except an MRS alteration in basal ganglia choline. Further studies are needed to assess CNS ATI safety in HIV remission trials, particularly for studies using higher thresholds to restart ART and longer ATI durations.

Incidence, clearance, persistence and factors related with high-risk anal HPV persistence in South-East Asian MSM and transgender women.

OBJECTIVES: Persistent anal high-risk human papillomavirus (HR-HPV) infection is a major risk factor for anal cancer among MSM and transgender women (TGW). We aimed to estimate incidence, clearance, and persistence of anal HR-HPV in HIV-positive and HIV-negative MSM and TGW, and to assess factors for HR-HPV persistence. DESIGN: Prospective cohort study. METHODS: MSM and TGW aged at least 18 years, were enrolled from Indonesia, Malaysia, and Thailand, then followed up 6-monthly for 12 months. Anal swabs were collected at every visit for HR-HPV genotypes to define anal HR-HPV incidence, clearance, and persistence. Logistic regression was used to evaluate factors associated with HR-HPV persistence. RESULTS: Three hundred and twenty-five MSM and TGW were included in this study, of whom 72.3% were HIV-positive. The incidence of anal HR-HPV persistence was higher in HIV-positive than HIV-negative MSM participants (28.4/1000 vs. 13.9/1000 person-months). HIV-positive participants had HR-HPV lower clearance rate than HIV-negative participants (OR 0.3; 95% CI 0.1-0.7). The overall persistence of HR-HPV was 39.9% in HIV-positive and 22.8% HIV-negative participants. HPV-16 was the most persistent HR-HPV in both HIV-positive and HIV-negative participants. HIV infection (aOR 2.87; 95% CI 1.47-5.61), living in Kuala Lumpur (aOR 4.99; 95% CI 2.22-11.19) and Bali (aOR 3.39; 95% CI 1.07-10.75), being employed/freelance (aOR 3.99; 95% CI 1.48-10.77), and not being circumcised (aOR 2.29; 95% CI 1.07-4.88) were independently associated with anal HR-HPV persistence. CONCLUSION: HIV-positive MSM and TGW had higher risk of persistent anal HR-HPV infection. Prevention program should be made available and prioritized for HIV-positive MSM and TGW where resources are limited.

Linkages to HIV confirmatory testing and antiretroviral therapy after online, supervised, HIV self-testing among Thai men who have sex with men and transgender women.

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.

Antiretroviral-naïve HIV-infected patients had lower bone formation markers than HIV-uninfected adults.

There are limited studies regarding bone health among people living with HIV (PLHIV) in Asia. We compared bone mineral density (BMD), serum 25-hydroxyvitamin D (25(OH)D) status and bone turnover markers (serum procollagen type1 N-terminal propeptide (P1NP), osteocalcin (OC) and C-terminal cross-linking telopeptide of type1 collagen) among 302 antiretroviral therapy (ART) naive PLHIV compared to 269 HIV-uninfected controls from Thailand. People aged ≥30 years, with and without HIV infection (free of diabetes, hypertension, and active opportunistic infection) were enrolled. BMD at the lumbar spine, total hip, and femoral neck were measured using Hologic DXA at baseline and at 5 years. We analyzed BMD, serum 25(OH)D levels, and bone turnover markers at the patients' baseline visit. PLHIV were 1.5 years younger and had lower BMI. PLHIV had higher mean serum 25(OH)D level and similar BMD to the controls. Interestingly, PLHIV had significantly lower bone formation (serum P1NP and OC), particularly those with low CD4 count. Only a few participants had low bone mass. ARV naïve middle-aged PLHIV did not have lower BMD or lower vitamin D levels compared to the controls. However, PLHIV had lower bone formation markers, particularly those with low CD4 count. This finding supports the benefit of early ART.

Discordance between self-perceived and actual risk of HIV infection among men who have sex with men and transgender women in Thailand: a cross-sectional assessment.

INTRODUCTION: Low uptake of HIV testing and services, including pre-exposure prophylaxis (PrEP), in Thai men who have sex with men (MSM) and transgender women (TGW) may be due to the inaccuracy in self-risk assessment. This study investigated the discordance between self-perceived HIV risk and actual risk. METHODS: Data were obtained between May 2015 and October 2016 from MSM and TGW enrolled in key population-led Test and Treat study in six community health centres in Thailand. Eligible participants were at least 18 years old, Thai national, had sex with men, had unprotected sex with a man in the past six months or had at least three male sex partners in the past six months, and were not known to be HIV positive. Baseline demographic behavioural characteristics questionnaires, including self-perceived HIV risk, were self-administered. Participants received HIV/STI (syphilis/gonorrhoea/chlamydia) testing at baseline. Participants who self-perceived to have low risk, but engaged in HIV-susceptible practices were categorized as having risk discordance (RD). Regression was conducted to assess factors associated with RD among MSM and TGW separately. RESULTS: Of the 882 MSM and 406 TGW participants who perceived themselves as having low HIV risk, over 80% reported at least one of the following: tested HIV positive, engaged in condomless sex, tested positive for a sexually transmitted infection sexually transmitted infection (STI; or used amphetamine-type stimulants. Logistic regression found that living with a male partner (p = 0.005), having never tested for HIV (p = 0.045), and living in Bangkok (p = 0.01) and Chiang Mai (p < 0.001) were associated with increased risk discordance among MSM. Living with a male partner (p = 0.002), being less than 17 years old at sexual debut (p = 0.001), and having a low knowledge score about HIV transmission (p < 0.001) were associated with increased risk discordance among TGW. However, for TGW, being a sex worker decreased the chance of risk discordance (p = 0.034). CONCLUSIONS: Future HIV prevention messages need to fill in the gap between self-perceived risk and actual risk in order to help HIV-vulnerable populations understand their risk better and proactively seek HIV prevention services.

Drug-drug interactions between feminizing hormone therapy and pre-exposure prophylaxis among transgender women: the iFACT study.

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.

High burden of chlamydia and gonorrhoea in pharyngeal, rectal and urethral sites among Thai transgender women: implications for anatomical site selection for the screening of STI.

OBJECTIVE: Comprehensive data on Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections to guide screening services among transgender women (TGW) are limited. We studied the burden of CT/NG infections in pharyngeal, rectal and urethral sites of Thai TGW and determined missed CT/NG diagnoses if selected site screening was performed. METHODS: Thai TGW were enrolled to the community-led test and treat cohort. CT/NG screening was performed from pharyngeal swab, rectal swab and urine using nucleic acid amplification test. CT/NG prevalence in each anatomical site was analysed, along with the relationships of CT/NG among the three anatomical sites. RESULTS: Of 764 TGW included in the analysis, 232 (30.4%) had CT/NG infections at any anatomical site, with an overall incidence of 23.7 per 100 person-years. The most common CT/NG infections by anatomical site were rectal CT (19.5%), rectal NG (9.6%) and pharyngeal NG (8.1%). Among 232 TGW with CT/NG infections at any anatomical site, 22%-94.4% of infections would have been missed if single anatomical site testing was conducted, depending on the selected site. Among 668 TGW who tested negative at pharyngeal site, 20.4% had either rectal or urethral infections. Among 583 TGW who tested negative at the rectal site, 8.7% had either pharyngeal or urethral infections. Among 751 TGW who tested negative at the urethral site, 19.2% had either pharyngeal or rectal infections. CONCLUSION: Almost one-third of Thai TGW had CT/NG infections. All-site screening is highly recommended to identify these infections, but if not feasible rectal screening provides the highest yield of CT/NG diagnoses. Affordable molecular technologies and/or CT/NG screening in pooled samples from different anatomical sites are urgently needed. TRIAL REGISTRATION NUMBER: NCT03580512.

What would you choose: Online or Offline or Mixed services? Feasibility of online HIV counselling and testing among Thai men who have sex with men and transgender women and factors associated with service uptake.

INTRODUCTION: HIV testing coverage remains low among men who have sex with men (MSM) and transgender women (TGW). We studied characteristics of Thai MSM and TGW who chose online and/or offline platforms for HIV counselling and testing and the feasibility of integrating online technologies and HIV self-testing to create service options. METHODS: From December 2015 to June 2017, MSM and TGW enrolled from Bangkok Metropolitan Region and Pattaya could choose between: offline HIV counselling and testing (Offline group), online pre-test counselling and offline HIV testing (Mixed group), and 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. Logistic regression models identified covariates for service preferences. RESULTS: Of 472 MSM and 99 TGW enrolled, 202 self-selected the Offline group, 158 preferred the Mixed group, and 211 chose the Online group. The Online group had the highest proportion of first-time testers (47.3% vs. 42.4% vs. 18.1%, p < 0.001) and reported highest HIV prevalence (15.9% vs. 13.0% vs. 3.4%, p = 0.001) as compared to Offline and Mixed groups, respectively. Having tested for HIV twice or more (OR 2.57, 95% CI 1.03 to 6.41, p = 0.04) increased the likelihood to choose online pre-test counselling. Being TGW (OR 6.66, 95% CI 2.91 to 15.25, p < 0.001) and using social media from four to eight hours (OR 2.82, 95% CI 1.48 to 5.37, p = 0.002) or >8 hours (OR 2.33, 95% CI 1.05 to 5.16, p = 0.04) increased selection of online, supervised, HIV self-testing. Providers primarily used smartphones (79.2%) and laptops (37.5%) to deliver online services. Self-testing strip image sharpness and colour quality were rated "good" to "excellent" by all providers. Most participants (95.1%) agreed that online supervision and HIV self-testing guidance offered were satisfactory and well delivered. CONCLUSIONS: Online HIV services among MSM and TGW are feasible in Thailand and have the potential to engage high proportions of first-time testers and those with high HIV prevalence. When designing public health interventions, integrating varied levels of online HIV services are vital to engage specific sections of MSM and TGW populations in HIV services. CLINICAL TRIAL NUMBER: NCT03203265.

Prevalence of and risk factors for anal high-risk HPV among HIV-negative and HIV-positive MSM and transgender women in three countries at South-East Asia.

This study aimed to assess the prevalence of and associated risk factors for anal high-risk human papillomavirus (hr-HPV) infection among men who have sex with men (MSM) and transgender women (TGW) in Indonesia, Thailand, and Malaysia.This was baseline data from a prospective cohort study with clinic sites in Jakarta and Bali (Indonesia), Bangkok (Thailand), and Kuala Lumpur (Malaysia).MSM and TGW aged 18 years and older from Indonesia, Thailand, and Malaysia were enrolled. Demographic and behavioral characteristics were assessed, and anal samples were collected for HPV genotyping. Multivariate logistic regression models were used to assess risk factors for anal hr-HPV overall and among HIV-positive participants.A total of 392 participants were enrolled, and 48 were TGW. As many as 245 were HIV-positive, and 78.0% of the participants were on combination antiretroviral therapy (cART). Median CD4 count was 439 cells/mm and 68.2% had undetectable HIV-RNA. HIV-positive participants had significantly more hr-HPV compared to HIV-negative participants (76.6% vs 53.5%, P < .001). HPV-16 was the most common high-risk type (20%), whereas HPV-33, -39, and -58 were significantly more common among HIV-positive participants. HIV-positive participant significantly associated with anal hr-HPV infection compared with HIV-negative (OR: 2.87, 95% CI: 1.76-4.70, P ≤ .001), whereas among HIV-positive participants transgender identity had lower prevalence of hr-HPV infection (OR: 0.42, 95% CI: 0.19-0.91, P = .03).High-risk HPV infection was very common among MSM and TGW in South-East Asia. Overall, HIV-infection, regardless of cART use and immune status, significantly increased the risk, while among HIV-positive participants transgender identity seemed to decrease the risk of anal hr-HPV.

Factors associated with intention to take non-occupational HIV post-exposure prophylaxis among Thai men who have sex with men.

BACKGROUND: Men who have sex with men (MSM) are disproportionately infected with HIV in Thailand. Factors affecting their intention to take non-occupational HIV post-exposure prophylaxis (nPEP) are not well understood. This study sought to determine factors associated with an intention to take nPEP in this population. METHOD: This is a two-phase mixed-method study. Phase I was a cross-sectional survey of intention to take nPEP in 450 MSM attending for HIV testing, using a self-administered questionnaire. Phase II was a prospective descriptive study, using an in-depth interview among 40 MSM who had been exposed to HIV in the past 72 hours. Multiple logistic regression was used to evaluate factors relating to the intention to use nPEP. RESULTS: Among 450 MSM seeking HIV testing in Bangkok, 7% had ever taken nPEP. Only 40% expressed an intention to take it to prevent HIV acquisition, despite the fact that they were at high risk as evidenced by an 18.9% prevalence of HIV-positive status. Factors associated with an intention to take nPEP were awareness about nPEP, HIV knowledge, mode of sexual intercourse and circumcision. Among 40 MSM who were eligible for and offered nPEP, 39 agreed to take it, and all but one completed the 4-week course. Condom use increased and all 32 individuals who could be contacted tested HIV negative after nPEP. CONCLUSION: A high HIV prevalence was found in MSM testing for HIV in this study. However, fewer than half of the participants expressed the intention to take nPEP if they were at risk for HIV infection. Efforts to create nPEP awareness and improve HIV knowledge in MSM are crucial to the successful implementation of nPEP as part of a combination package for HIV prevention in this high-risk population.

Improved adipose tissue function with initiation of protease inhibitor-only ART.

OBJECTIVES: Use of ART containing HIV PIs has previously been associated with toxicity in subcutaneous adipose tissue (SAT), potentially contributing to the development of lipodystrophy and insulin resistance. However, the effect of PIs on SAT function in ART-naive patients independent of other ART classes is unknown. This study aimed to elucidate the effect of initiating PI-only ART on SAT function in ART-naive subjects. METHODS: In the HIVNAT-019 study, 48 HIV-infected, ART-naive Thai adults commencing PI-only ART comprising lopinavir/ritonavir/saquinavir for 24 weeks underwent assessments of fasting metabolic parameters and body composition. In a molecular substudy, 20 subjects underwent SAT biopsies at weeks 0, 2 and 24 for transcriptional, protein, mitochondrial DNA (mtDNA) and histological analyses. ClinicalTrials.gov registration number: NCT00400738. RESULTS: Over 24 weeks, limb fat increased (+416.4 g, P = 0.023), coinciding with larger adipocytes as indicated by decreased adipocyte density in biopsies (-32.3 cells/mm2, P = 0.047) and increased mRNA expression of adipogenesis regulator PPARG at week 2 (+58.1%, P = 0.003). Increases in mtDNA over 24 weeks (+600 copies/cell, P = 0.041), decreased NRF1 mRNA expression at week 2 (-33.7%, P < 0.001) and increased COX2/COX4 protein ratio at week 24 (+288%, P = 0.038) indicated improved mitochondrial function. Despite decreased AKT2 mRNA at week 2 (-28.6%, P = 0.002) and increased PTPN1 mRNA at week 24 (+50.3%, P = 0.016) suggesting insulin resistance, clinical insulin sensitivity [by homeostasis model assessment (HOMA-IR)] was unchanged. CONCLUSIONS: Initiation of PI-only ART showed little evidence of SAT toxicity, the changes observed being consistent with a return to health rather than contributing to lipodystrophy.

High prevalence of transmitted drug resistance in acute HIV-infected Thai men who have sex with men.

: As use of antiretroviral therapy in Thailand increases, so does the potential for transmission of drug-resistant HIV. We describe the prevalence of WHO surveillance drug resistance mutations among 120 subjects who underwent genotypic testing during acute HIV infection in Bangkok, Thailand. In this cohort of predominantly men who have sex with men, we observed an overall transmitted drug resistance prevalence of 9.2%, including nucleoside/nucleotide analog reverse transcriptase inhibitor 5.0%, nonnucleoside analog reverse transcriptase inhibitor 3.4%, and protease inhibitor 3.4%. These prevalence estimates are higher than previous reports of transmitted drug resistance in Thailand. Baseline drug resistance testing may be warranted, particularly among men who have sex with men.

Cervical and anal HPV infection: cytological and histological abnormalities in HIV-infected women in Thailand.

BACKGROUND: Women infected with human immunodeficiency virus (HIV) have higher rates of persistent infection with high-risk human papillomavirus (hr-HPV) and cervical and anal dysplasia. We describe the epidemiology of hr-HPV, and cervical and anal intra-epithelial abnormalities in HIV-infected women in Thailand. METHODS: HIV-infected women aged 18-49 years, either HAART-naïve or -experienced, were enrolled in Bangkok, Thailand. A demographic and sexual-risk behaviour questionnaire was administered and a pelvic examination with colposcopy was performed on every woman. Cervical and anal samples were tested for cytology and HPV genotyping. RESULTS: A total of 256 women were enrolled with a median [interquartile range (IQR)] age of 35 (32-40) years. Ninety (35.2%) had detectable cervical hr-HPV. Being post-menopausal was associated with increased risk for cervical hr-HPV, while years since HIV diagnosis and plasma HIV RNA <40 copies/mL were significantly associated with decreased risk in multivariable regression analyses. Abnormal cervical cytology was detected in 6.3%. Cervical biopsies that were taken from 99 women (39.3%) owing to abnormalities seen during colposcopy showed cervical intra-epithelial neoplasia (CIN) in 22.6%. The sensitivity of cervical cytology to detect CIN2+ was 10.0%. Among 102 women enrolled in the anal substudy, 18.8% had anal HPV infection and 11.1% had anal hr-HPV. Two women had abnormal anal cytology. CONCLUSION: We found cervical and anal hr-HPV in 35.2% and 11.1% of Thai HIV-infected women, respectively. Moreover, the observed poor agreement between cervical cytology and histology results could indicate current cervical cancer screening programs for HIV-infected women might not be optimal for the detection of pre-neoplastic lesions.

Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation.

Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation.

HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia.

INTRODUCTION: First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. METHODS: We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance - Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥ 2 TAMs; or M184V+≥ 1 TAM. Virological suppression was defined as viral load (VL) <400 copies/ml at 12 months from switch to second-line. Logistic regression was used to analyze (1) factors associated with multi-NRTI RAMs at first-line failure and (2) factors associated with virological suppression after 12 months on second-line. RESULTS: A total of 105 patients from 10 sites in Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥ 1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥ 2 TAMs; and 32 with M184V+≥ 1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤ 200 cells/µL at genotyping (OR=4.43, 95% CI [1.59-12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39-16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ≥ 95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43-35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome. CONCLUSIONS: Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second-line therapy.