Prevalence and incidence of anal high-grade squamous intraepithelial lesions in a cohort of cisgender men and transgender women who have sex with men diagnosed and treated during acute HIV acquisition in Bangkok, Thailand.

INTRODUCTION: Men who have sex with men (MSM), especially those living with HIV, are at an increased risk of anal cancer. The prevalence and incidence of its precursor, anal high-grade squamous intraepithelial lesions (HSILs), among MSM who started antiretroviral therapy during acute HIV acquisition are yet to be explored. METHODS: Participants in an acute HIV acquisition cohort in Bangkok, Thailand, who agreed to take part in this study, were enrolled. All participants were diagnosed and started antiretroviral therapy during acute HIV acquisition. Human papillomavirus (HPV) genotyping and high-resolution anoscopy, followed by anal biopsy as indicated, were done at baseline and 6-monthly visits. RESULTS: A total of 89 MSM and four transgender women were included in the analyses. Median age at enrolment was 26 years. Baseline prevalence of histologic anal HSIL was 11.8%. With a total of 147.0 person-years of follow-up, the incidence of initial histologic anal HSIL was 19.7 per 100 person-years. Factors associated with incident anal HSIL were anal HPV 16 (adjusted hazards ratio [aHR] 4.33, 95% CI 1.03-18.18), anal HPV 18/45 (aHR 6.82, 95% CI 1.57-29.51), other anal high-risk HPV (aHR 4.23, 95% CI 1.27-14.14), syphilis infection (aHR 4.67, 95% CI 1.10-19.90) and CD4 count <350 cells/mm3 (aHR 3.09, 95% CI 1.28-7.48). CONCLUSIONS: With antiretroviral therapy initiation during acute HIV acquisition, we found the prevalence of anal HSIL among cisgender men and transgender women who have sex with men to be similar to those without HIV. Subsequent anal HSIL incidence, although lower than that of those with chronic HIV acquisition, was still higher than that of those without HIV. Screening for and management of anal HSIL should be a crucial part of long-term HIV care for all MSM.

The effects of bivalent human papillomavirus (HPV) vaccination on high-risk anogenital HPV infection among sexually active female adolescents with and without perinatally acquired HIV.

BACKGROUND: Females with perinatal HIV (PHIV) infection are at elevated risk for anogenital high-risk human papillomavirus (HR-HPV) infection. Limited data are available around the effect of the HPV vaccination after initiation of sexual activity among PHIV youth. This study aims to assess the impact of a bivalent HPV vaccination on the persistence of anogenital HR-HPV among sexually active female PHIV youth and matched HIV-negative controls aged 12-24years in Thailand and Vietnam. METHODS: During a 3-year study, prevalent, incident, and persistent HR-HPV infection were assessed at annual visits. A subset of participants received a bivalent HPV vaccine. Samples were taken for HPV testing from the vagina, cervix, and anus. HR-HPV persistence was defined as the detection of the same genotype(s) at any anogenital compartment over≥two consecutive visits. RESULTS: Of the 93 PHIV and 99 HIV-negative female youth enrolled in this study, 25 (27%) PHIV and 22 (22%) HIV-negative youth received a HPV vaccine. Persistent infection with any HR-HPV type was significantly lower among PHIV youth who received the vaccine compared to those who did not (33%vs 61%, P =0.02); a difference was not observed among HIV-negative youth (35%vs 50%, P =0.82). PHIV infection (adjusted prevalence ratio [aPR] 2.31, 95% CI 1.45-3.67) and not receiving a HPV vaccine (aPR, 1.19, 95%CI 1.06-1.33) were associated with persistent anogenital HR-HPV infection. CONCLUSIONS: Bivalent HPV vaccination after initiation of sexual activity was associated with reduced persistence of anogenital HR-HPV infection in Southeast Asian PHIV female youth, which may be related to vaccine cross-protection. Primary and catch-up HPV vaccinations should be prioritised for children and youth with HIV.

Estradiol and Testosterone Concentrations Among Thai Transgender Women in a Transgender-Led, Integrated Gender-Affirming Care and Sexual Health Clinic: A Real-World Analysis.

Purpose: Feminizing hormone therapy (FHT) is used by many transgender women as a pharmacological method to mitigate gender dysphoria. However, information on hormone concentrations among those who use FHT is lacking. We aimed to determine the proportion of Thai transgender women who were using FHT who had hormone concentrations within target ranges in a real-world clinic setting. Methods: Transgender women who attended Tangerine Clinic in Bangkok, Thailand, reported current use of FHT at clinic entry, and tested for both blood estradiol (E2) and total testosterone (TT) concentrations were included in the analysis. Hormone target concentrations were defined as 100-200 pg/mL for E2 and <50 ng/dL for TT. Results: Of 1534 transgender women included, 2.5% had undergone orchiectomy, and 524 (34.2%) had any hormones within target concentrations. Median (interquartile range) E2 and TT concentrations at baseline were 29 (14.3-45.3) pg/mL and 298.5 (22-646) ng/dL, respectively. Among those who had any hormones within target concentrations, 28 (1.8%), 11 (0.7%), and 485 (31.6%) had both hormones, only E2, and only TT within target concentrations, respectively. Among 1010 (65.8%) transgender women who had neither hormone within target concentrations, 989 (64.5%) and 21 (1.4%) had suboptimal and supraphysiological E2 concentrations, respectively. Among those who came to at least one follow-up visit (n=302), 165 (54.6%) transgender women managed to achieve or maintain either hormone within target concentrations. Conclusion: One-third of Thai transgender women who were using FHT had any hormones within target concentrations at baseline in this real-world setting study. Most transgender women who had neither hormone within target concentrations had suboptimal rather than supraphysiological E2 concentrations. More than half managed to achieve or maintain at least one hormone concentration within target concentrations at follow-up visits, suggesting a positive effect from attending a trans-led, integrated gender-affirming care and sexual health service.

Same-day antiretroviral therapy initiation hub model at the Thai Red Cross Anonymous Clinic in Bangkok, Thailand: an observational cohort study.

INTRODUCTION: WHO has recommended rapid antiretroviral therapy (ART) initiation, including same-day ART (SDART). However, data on the feasibility in real-world settings are limited. We implemented a cohort study at a stand-alone HIV testing centre to examine its applicability and effectiveness. METHODS: Data were collected from the Thai Red Cross Anonymous Clinic in Bangkok, Thailand, between July 2017 and July 2018 from clients who were ART-naïve and could return for follow-up visits. Baseline laboratory tests and chest X-ray were performed according to national guidelines, and clinical eligibility was determined based on physical examination and chest X-ray findings. Primary outcomes were retention in care and viral load suppression at 3, 6 and 12 months. RESULTS: During the study period, 2427 people tested HIV positive. Of these, 2107 (2207/2427, 86.8%) met logistical criteria, and 1904 (1904/2427, 78.5%) agreed to SDART. One thousand seven hundred and twenty-nine (1729/2427, 71.2%) were placed on ART, with 1257 received same-day initiation and 1576 initiated ART within 7 days; 1198 clients were successfully referred to free, sustained ART sites. Retention among eligible clients who accepted SDART service at months 3, 6 and 12 was 79.8%, 75.2% and 75.3%, respectively. CONCLUSIONS: Same-day ART initiation hub model at a stand-alone HIV testing centre in an urban setting in Bangkok, Thailand, is highly feasible and has a potential for scaling up. CLINICAL TRIAL NUMBER: NCT04032028.

Evaluation of the integration of telehealth into the same-day antiretroviral therapy initiation service in Bangkok, Thailand in response to COVID-19: a mixed-method analysis of real-world data.

INTRODUCTION: Same-day antiretroviral therapy (SDART) initiation has been implemented at the Thai Red Cross Anonymous Clinic (TRCAC) in Bangkok, Thailand, since 2017. HIV-positive, antiretroviral therapy (ART)-naïve clients who are willing and clinically eligible start ART on the day of HIV diagnosis. In response to the first wave of the coronavirus disease 2019 (COVID-19) outbreak in March 2020, telehealth follow-up was established to comply with COVID-19 preventive measures and allow service continuation. Here, we evaluate its implementation. METHODS: Pre-COVID-19 (until February 2020) clients who initiated SDART received a 2-week ART supply and returned to the clinic for evaluation before being referred to long-term ART maintenance facilities. If no adverse events (AEs) occurred, another 8-week ART supply was provided while referral was arranged. During the first wave of COVID-19 (March-May 2020), clients received a 4-week ART supply and the option of conducting follow-up consultation and physical examination via video call. Clients with severe AEs were required to return to TRCAC; those without received another 6-week ART supply by courier to bridge transition to long-term facilities. This adaptation continued post-first wave (May-August 2020). Routine service data were analysed using data from March to August 2019 for the pre-COVID-19 period. Interviews and thematic analysis were conducted to understand experiences of clients and providers, and gain feedback for service improvement. RESULTS: Of 922, 183 and 321 eligible clients from the three periods, SDART reach [89.9%, 96.2% and 92.2% (p = 0.018)] and ART initiation rates [88.1%, 90.9% and 94.9% (p<0.001)] were high. ART uptake, time to ART initiation and rates of follow-up completion improved over time. After the integration, 35.3% received the telehealth follow-up. The rates of successful referral to a long-term facility (91.8% vs. 95.3%, p = 0.535) and retention in care at months 3 (97.5% vs. 98.0%, p = 0.963) and 6 (94.1% vs. 98.4%, p = 0.148) were comparable for those receiving in-person and telehealth follow-up. Six clients and nine providers were interviewed; six themes on service experience and feedback were identified. CONCLUSIONS: Telehealth follow-up with ART delivery for SDART clients is a feasible option to differentiate ART initiation services at TRCAC, which led to its incorporation into routine service.

Acceptability and satisfaction towards self-collection for chlamydia and gonorrhoea testing among transgender women in Tangerine Clinic, Thailand: shifting towards the new normal.

INTRODUCTION: Provider-collected swabs are an unappealing procedure for many transgender women and may have led to suboptimal rates of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) testing. Self-collection for CT/NG testing is recommended for men who have sex with men. However, the information on acceptability and clinical performance to support a recommendation for transgender women is lacking. We aimed to determine the acceptability and satisfaction towards self-collection for CT/NG testing among Thai transgender women. METHODS: Thai transgender women who attended Tangerine Clinic (a transgender-led, integrated, gender-affirming care and sexual health services clinic in Bangkok, Thailand) between May and July 2020 and had condomless sexual intercourse within the past six months were offered to collect urine and perform self-swabs of pharyngeal, rectal, and if applicable, neovaginal compartments for pooled nucleic acid amplification testing for CT/NG infections. Participants received a diagram, video and oral instructions about how to perform self-collection procedure. Those who accepted self-collection were also offered to receive provider collection to evaluate the performance between the two methods. Self-administered questionnaires were used to assess satisfaction. RESULTS: Among 216 transgender women enrolled, 142 (65.7%) accepted self-collection. All who accepted had pharyngeal, rectal and urine samples collected. Of 31 transgender women who had undergone genital surgery, 28 (90.3%) accepted neovaginal self-swab. The acceptance rate increased from 46.2% in May to 84.5% in July 2020. One participant had an invalid result. All transgender women who accepted self-collection could perform it without assistance, and 82.8% were highly satisfied with the method. None reported dissatisfaction. Due to the COVID-19 pandemic, provider collection services were discontinued early, and only eight transgender women were able to perform both methods for performance evaluation. The performance agreement was 100%. CONCLUSIONS: Thai transgender women had high acceptability and satisfaction towards self-collection for CT/NG testing. The performance was promising compared to provider collection. Our results support the implementation of self-collection to the sexually transmitted infection services, particularly during the COVID-19 pandemic where physical distancing is the new normal. A larger study is warranted to determine the performance of self-collection for CT/NG testing in each anatomical compartment and confirm the performance between self-collection and provider collection.

Uptake of Primary Care Services and HIV and Syphilis Infection among Transgender Women attending the Tangerine Community Health Clinic, Bangkok, Thailand, 2016 - 2019.

INTRODUCTION: Transgender women (TGW) need a specific package of primary care services usually not available in the publicly funded healthcare system. In addition, little is known about HIV and syphilis prevalence and incidence in clinic-based samples of TGW. Here we evaluate the uptake of a transgender-specific package of primary care services by TGW in Bangkok, Thailand and assess HIV and syphilis prevalence and incidence among them. METHODS: Open cohort study of TGW attending services at the Tangerine Community Health Clinic from 2016 to 2019. Cross-sectional and longitudinal analysis of routinely collected clinic data was performed to study trends in the number of clients, clinic visits and HIV and syphilis prevalence and incidence. RESULTS: During the study period, 2947 TGW clients made a total of 5227 visits to Tangerine. The number of clients significantly increased from 446 in 2016 to 1050 in 2019 (p < 0.001) and the number of visits from 616 to 2198 during the same period (p < 0.001). Prevalence of HIV at first visit was 10.8% and of syphilis 9.8%. HIV incidence was 1.03 per 100 person years (PY) and of syphilis 2.06 per 100 PY of follow-up. From 2016 to 2019, significant decreases occurred in the annual prevalence of HIV from 14.6% to 9.9% (p < 0.01). The annual prevalence of syphilis significantly increased from 6.6% in 2016 to 14.6% in 2018, and then decreased to 7.3% in 2019 (p < 0.001). The annual HIV incidence decreased during 2016 to 2019, from 1.68 to 1.28 per 100 PY, but this reduction was not statistically significant. The annual incidence of treponemal test seroconversion significantly increased from zero in 2016 to 4.55 per 100 PY in 2019 (p < 0.001). CONCLUSIONS: The increasing uptake of a transgender-specific package of services, including co-located gender affirmative hormone therapy, suggests this may be an effective model in engaging and retaining TGW in primary care. The decrease in HIV prevalence and low HIV incidence across calendar years point at a possible reduction of HIV acquisition among the TGW population served by Tangerine. The increasing prevalence of syphilis suggests ongoing high-risk sexual behaviour and underscores the need for screening and treatment for this infection at the time of delivery of HIV services.

Neovaginal and Anal High-Risk Human Papillomavirus DNA Among Thai Transgender Women in Gender Health Clinics.

BACKGROUND: Although human papillomavirus (HPV)-related lesions in the neovagina of transgender women have been well documented, information on high-risk HPV (hrHPV) in the neovagina has been very limited. The objective of this study was to determine hrHPV DNA detection rate in the neovagina of transgender women. METHODS: Neovaginal and anal swab were collected in liquid-based cytology fluid from transgender women visiting Gender Health Clinic and Tangerine Community Health Clinic in Bangkok, Thailand. Samples were processed for hrHPV DNA (reported as subtypes 16 and 18 or the pooled result of subtypes 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) by automated real-time polymerase chain reaction and for neovaginal cytology according to the Bethesda system. Demographic data and sexual history were obtained, and physical examination was conducted. HIV status was obtained from existing medical records. RESULTS: Samples were collected from 57 transgender women (mean age, 30.4 years [interquartile range, 8 years]). From 35 of 57 valid neovaginal samples, 8 (20%) tested positive for hrHPV DNA. From 30 of 57 valid anal samples, 6 (19.4%) tested positive for hrHPV DNA. HIV status was known for 52 transgender women, 1 of which were HIV infected; neovaginal hrHPV was invalid in that patient. CONCLUSIONS: One of 5 transgender women visiting sexual health clinics in Bangkok was found to have hrHPV DNA in neovaginal and anal compartments. Studies are needed to look at incidence and persistence of hrHPV infection to inform anogenital precancerous and cancerous screening programs for transgender women.

Increased Burden of Concordant and Sequential Anogenital Human Papillomavirus Infections Among Asian Young Adult Women With Perinatally Acquired HIV Compared With HIV-Negative Peers.

BACKGROUND: Youth with perinatally acquired HIV (YPHIV) are at higher risk for anogenital human papillomavirus (HPV) infection. METHODS: We enrolled a cohort of YPHIV and HIV-negative youth in Thailand and Vietnam, matched by age and lifetime sex partners, and followed them up for 144 weeks (to 2017). Participants had annual pelvic examinations with samples taken for HPV genotyping. Concordant infection was simultaneous HPV detection in multiple anogenital compartments (cervical, vaginal, anal); sequential infection was when the same type was found in successive compartments (cervicovaginal to/from anal). Generalized estimating equations were used to assess factors associated with concordant infection, and Cox regression was used to assess factors associated with sequential infection. RESULTS: A total of 93 YPHIV and 99 HIV-negative women were enrolled, with a median age of 19 years (interquartile range, 18-20 years). High-risk anogenital HPV infection was ever detected in 76 (82%) YPHIV and 66 (67%) HIV-negative youth during follow-up. Concordant anogenital high-risk HPV infection was found in 62 (66%) YPHIV versus 44 (34%) HIV-negative youth. Sequential cervicovaginal to anal high-risk HPV infection occurred in 20 YPHIV versus 5 HIV-negative youth, with an incidence rate of 9.76 (6.30-15.13) versus 2.24 (0.93-5.38) per 100 person-years. Anal to cervicovaginal infection occurred in 4 YPHIV versus 0 HIV-negative women, with an incidence rate of 1.78 (0.67-4.75) per 100 person-years. Perinatally acquired HIV was the one factor independently associated with both concordant and sequential high-risk HPV infection. CONCLUSIONS: Children and adolescents with perinatally acquired HIV should be prioritized for HPV vaccination, and cervical cancer screening should be part of routine HIV care for sexually active YPHIV.

Incidence, Persistence, and Factors Associated With HPV Infection Among Male Adolescents With and Without Perinatally Acquired HIV Infection.

BACKGROUND: Infection with high-risk human papillomavirus (HR-HPV) has been shown to be more prevalent and persistent in female adolescents with HIV. However, data among male adolescents with perinatally acquired HIV (PHIV) are limited. SETTING: We investigated the incidence and persistence of HR-HPV in anogenital compartments and associated factors among PHIV in comparison to HIV-uninfected (HU) male adolescents in Thailand. METHODS: PHIV and HU males aged 12-24 years were enrolled. At baseline and 3 subsequent annual visits, specimens from the scrotum, penis, and anal area were obtained for HPV and other testing. RESULTS: From June 2013 to October 2017, 49 PHIV and 47 HU male adolescents with a median age of 18 (interquartile range 17-20) years were enrolled. PHIV had higher incidence of any HR-HPV infection than HU adolescents {33.05 [95% confidence interval (CI): 20.82 to 52.46] vs. 15.73 [95% CI: 8.18 to 30.22] per 100 person-years, P = 0.04}. The persistence of any HR-HPV genotypes (detected at ≥2 annual visits) was not different by group (PHIV 27% vs. HU 23%, P = 0.75). Having ≥3 sex partners in past 6 months (adjusted prevalence ratio 2.39, 95% CI: 1.14 to 5.05; P = 0.02) and co-infection with other sexually transmitted infections (syphilis, chlamydia, and/or gonorrhea) were associated with persistent HR-HPV infection (adjusted prevalence ratio 6.21, 95% CI: 2.87 to 13.41; P < 0.001). CONCLUSIONS: Thai PHIV male adolescents had a higher incidence of HR-HPV infection than those without HIV. Having multiple sex partners and co-infection with sexually transmitted infections was associated with persistent HR-HPV infection. These data demonstrate the need to prioritize PHIV male adolescents in routine and catch-up HPV vaccination programs.

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.

Prevalence of High-risk Nonavalent Vaccine-type Human Papillomavirus Infection Among Unvaccinated, Sexually Active Asian Female Adolescents With and Without Perinatally Acquired HIV Infection.

BACKGROUND: We studied the prevalence of 7, high-risk human papillomavirus (HPV) types in the nonavalent vaccine (HRVT-7: HPV 16, 18, 31, 33, 45, 52, 58) among vaccine-naïve, sexually active Asian female adolescents with and without perinatally acquired HIV infection (PHIV). METHODS: PHIV female adolescents 12-24 years of age and HIV-uninfected controls matched by age and number of lifetime sex partners were enrolled in a 3-year observational cohort study in Thailand and Vietnam. Samples from the oral cavity, anus, cervix and vagina were collected for HRVT-7 HPV genotyping, and serum collected for HPV 16 and 18 antibody testing. Baseline data were analyzed using multivariable logistic regression. RESULTS: We included 93 PHIV (median CD4 593 cells/mm, 62% with HIV RNA suppression) and 99 HIV-uninfected adolescents (median lifetime sex partners 2). The overall prevalence of HRVT-7 infection was 53% in PHIV and 49% in HIV-uninfected adolescents (P = 0.66). Cervical HRVT-7 DNA was detected more frequently in PHIV than HIV-uninfected adolescents (37% vs. 23%, P = 0.04). Overall, more lifetime partners [≥3 vs. 1; odds ratio (OR) 2.99 (1.38-6.51), P = 0.02] and having other sexually transmitted infections [OR 3.30 (1.51-7.21), P = 0.003] increased the risk of HRVT-7 infection and/or positive HPV 16/18 antibodies; while detectable HIV RNA [OR 2.78 (1.05-7.36), P = 0.04] increased the risk among PHIV adolescents. CONCLUSIONS: Half of sexually active Asian female adolescents, regardless of HIV infection, had already acquired HRVT-7 infection. This underscores the need for earlier access to HPV vaccine in the region.

Bone mineral density changes among people living with HIV who have started with TDF-containing regimen: A five-year prospective study.

There are limited data regarding long-term BMD changes over time among treatment-naïve people living with HIV (PLHIV) after initiating combined antiretroviral therapy (cART) in Asia. We aimed to study bone mineral density (BMD) changes among treatment-naïve PLHIV started treatment with tenofovir disoproxil fumarate (TDF)- or non-TDF-containing regimen and HIV-uninfected controls in an Asian setting. The study was a five-year prospective study. BMD at lumbar spine (LS) (L1 to L4), total hip (TH), and femoral neck (FN) were measured by dual energy X-ray absorptiometry (DEXA) scans at baseline, months 12, 24 and 60. Multivariate logistic regression models were used to explore factors associated with mean BMD ≥5% reduction after 5 years of cART. A total of 106 PLHIV (75 and 31 started TDF- and non-TDF-containing regimen, respectively) and 66 HIV-uninfected individuals were enrolled. The mean percent changes of BMD were significantly different longitudinally between TDF and non-TDF users (p<0.001 for LS, p = 0.006 for TH and p = 0.02 for FN). HIV-positive status and on TDF-containing regimen was independently associated with BMD loss ≥5% at month 60 (adjusted odds ratio [aOR] 7.0, 95% confidence interval [95%CI] 2.3-21.0, P = 0.001 for LS; aOR 4.9, 95%CI 1.7-14.3, P = 0.003 for TH and aOR 4.3, 95%CI 1.6-11.2, P = 0.003 for FN) compared to HIV-uninfected individuals. In a multivariate model for PLHIV only, TDF use (vs. non-TDF, P = 0.005) and pre-treatment CD4+ count <350 cells/mm3 (vs. ≥350 cells/mm3, P = 0.02) were independently associated with ≥5% BMD loss in TH at month 60. Treatment-naïve PLHIV initiating treatment with TDF-containing regimen have higher BMD loss in a Thai cohort. TDF use and low pre-treatment CD4 count were independently associated with BMD loss at month 60 at TH. Earlier treatment initiation and interventions to prevent bone loss could improve skeletal health among PLHIV. Clinicaltrials.gov: NCT01634607.

Prospective International Study of Incidence and Predictors of Immune Reconstitution Inflammatory Syndrome and Death in People Living With Human Immunodeficiency Virus and Severe Lymphopenia.

BACKGROUND: Patients living with human immunodeficiency virus (PLWH) with low CD4 counts are at high risk for immune reconstitution inflammatory syndrome (IRIS) and death at antiretroviral therapy (ART) initiation. METHODS: We investigated the clinical impact of IRIS in PLWH and CD4 counts <100 cells/µL starting ART in an international, prospective study in the United States, Thailand, and Kenya. An independent review committee adjudicated IRIS events. We assessed associations between baseline biomarkers, IRIS, immune recovery at week 48, and death by week 48 with Cox models. RESULTS: We enrolled 506 participants (39.3% were women). Median age was 37 years, and CD4 count was 29 cells/µL. Within 6 months of ART, 97 (19.2%) participants developed IRIS and 31 (6.5%) died. Participants with lower hemoglobin at baseline were at higher IRIS risk (hazard ratio [HR], 1.2; P = .004). IRIS was independently associated with increased risk of death after adjustment for known risk factors (HR, 3.2; P = .031). Being female (P = .004) and having a lower body mass index (BMI; P = .003), higher white blood cell count (P = .005), and higher D-dimer levels (P = .044) were also significantly associated with increased risk of death. Decision-tree analysis identified hemoglobin <8.5 g/dL as predictive of IRIS and C-reactive protein (CRP) >106 µg/mL and BMI <15.6 kg/m2 as predictive of death. CONCLUSIONS: For PLWH with severe immunosuppression initiating ART, baseline low BMI and hemoglobin and high CRP and D-dimer levels may be clinically useful predictors of IRIS and death risk.

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.

Incidence and Persistence of High-risk Anogenital Human Papillomavirus Infection Among Female Youth With and Without Perinatally Acquired Human Immunodefiency Virus Infection: A 3-year Observational Cohort Study.

BACKGROUND: Female youth with perinatally acquired human immunodeficiency virus (PHIV) may be at higher risk than uninfected youth for persistent anogenital human papillomavirus (HPV) infection, due to prolonged immunodeficiency. METHODS: A 3-year cohort study was conducted between 2013 and 2017 among Thai and Vietnamese PHIV and HIV-uninfected females 12-24 years, matched by age group and number of lifetime sexual partners. For HPV genotyping, cervical and anal samples were obtained at baseline and annually. Vaginal samples were collected at baseline and every 6 months. Factors associated with high-risk HPV (HR-HPV) persistence and incidence were assessed. RESULTS: We enrolled 93 PHIV and 99 HIV-uninfected females. Median age was 19 (interquartile range [IQR] 18-20) years. For the 7 HR-HPV types (16, 18, 31, 33, 45, 52, 58) in the nonavalent HPV vaccine, PHIV had significantly higher incidence (P = .03) and persistence (P = .01) than HIV-uninfected youth over a 3-year period. Having HIV (adjusted hazard ratio [aHR] 2.1, 95% confidence interval [CI] 1.1-3.9) and ever using illegal substances (aHR 4.8, 95% CI 1.8-13.0) were associated with incident 7 HR-HPV infections. HIV-positive status (adjusted prevalence ratio [aPR] 2.2, 95% CI 1.5-3.2), recent alcohol use (aPR 1.75, 95% CI 1.2-2.5), and higher number of lifetime partners (aPR 2.0, 95% CI 1.4-3.1, for 3-5 partners; aPR 1.93, 95% CI 1.2-3.2, for ≥6 partners) were significantly associated with persistent 7 HR-HPV infections. CONCLUSIONS: Female PHIV were at higher risk of having anogenital HR-HPV acquisition and persistence. Primary and secondary prevention programs for HPV infection and HPV-related diseases should be prioritized for PHIV children and youth.

Changes in risk behaviors among Thai men who have sex with men and transgender women enrolled in the test and treat cohort.

The test-and-treat approach has the potential to reduce high-risk sexual behaviors by linking high-risk individuals to health education, although this has not been proven yet. We used longitudinal data from the Test and Treat Demonstration Project among Thai men who have sex with men (MSM) and transgender women (TGW) who were not known to be HIV-positive to analyze changes in risk behaviors during the 24-month study period categorized by three groups: HIV-negative without seroconversion, seroconverters, and HIV-positive at enrollment. Five binary risk behavior outcomes - laboratory-diagnosed sexually transmitted infections (STIs); multiple sexual partners, unprotected anal intercourse, self-perceived HIV risk, and amphetamine-type stimulants use in the past month - were assessed. Among 689 participants, with a mean (SD) age of 23.1 (6.2) years, 165 participants were diagnosed with HIV: 115 at enrollment and 50 with seroconversions. HIV-positive participants at enrollment showed significant reductions in all five behavioral risk outcomes. Seroconverters demonstrated higher risks at enrollment than HIV-negative participants, and continued to practice high-risk behaviors even after seroconversion despite a significant reduction in self-perceived moderate-to-high HIV risk. Continuation of risk behaviors among seroconverters could negatively affect the ending AIDS goal, thus the integration of other effective preventive measures into HIV/STIs management programs are needed.

High subsequent and recurrent sexually transmitted infection prevalence among newly diagnosed HIV-positive Thai men who have sex with men and transgender women in the Test and Treat cohort.

We determined subsequent and recurrent sexually transmitted infections (STIs) among men who have sex with men (MSM) and transgender women (TGW) in the Test and Treat cohort. Thai MSM and TGW adults with previously unknown HIV status were enrolled and tested for HIV. Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and syphilis were tested at baseline, month 12, and month 24 to identify subsequent STIs (any STIs diagnosed after baseline) and recurrent STIs (any subsequent STIs diagnosed among those with positive baseline STIs). Among 448 participants, 17.8% were HIV-positive, the prevalence of subsequent STIs and recurrent STIs was 42% (HIV-positive versus HIV-negative: 66.3% versus 36.7%, p < 0.001) and 62.3% (81% versus 52.5%, p < 0.001), respectively. Common subsequent STIs by anatomical site were rectal CT infection (21.7%), rectal NG infection (13.8%), pharyngeal NG infection (13.1%), and syphilis (11.9%). HIV-positive status was associated with both subsequent STIs (adjusted hazard ratio [aHR] 2.38; 95%CI 1.64-3.45, p < 0.001) and recurrent STIs (aHR 1.83; 95%CI 1.16-2.87, p = 0.01). The results show that newly diagnosed HIV-positive MSM and TGW were at increased risk of STIs despite being in the healthcare system. STI educational counseling is necessary to improve STI outcomes among MSM and TGW in both HIV prevention and treatment programs.

Sexually transmitted infections and HIV RNA levels in blood and anogenital compartments among Thai men who have sex with men before and after antiretroviral therapy: implication for Treatment as Prevention programme.

INTRODUCTION: Sexually transmitted infections (STIs) are common among HIV-positive men who have sex with men (MSM). There have been concerns that undiagnosed and untreated STIs could undermine efforts to use antiretroviral therapy (ART) for prevention due to genital secretion infectiousness. We evaluated the correlation between STIs and HIV RNA in anogenital compartments among HIV-positive MSM before and after ART. METHODS: MSM participants newly diagnosed with HIV were offered ART regardless of CD4 count during November 2012 to November 2015. Syphilis serology, oropharyngeal swab, rectal swab, urine collection for gonorrhoea and chlamydia nucleic acid amplification testing, and HIV RNA measurement in blood, semen and rectal samples were performed at baseline, 12 and 24 months thereafter. RESULTS: Of 143 HIV-positive MSM, 16.1% had syphilis, 23.1% had gonorrhoea and 32.8% had chlamydia at baseline. Participants with STIs at baseline had higher median HIV RNA levels in blood plasma (p = 0.053), seminal plasma (p = 0.01) and rectal secretions (p = 0.002) than those without STIs. Multivariate models identified HIV RNA 100,000 to 500,000 (OR 6.74, 95% CI 2.24 to 20.28, p = 0.001) and >500,000 (OR 9.39, 95% CI 1.08 to 81.72, p = 0.04) copies/mL in blood, CD4 count <350 cells/mm3 (OR 4.20, 95% CI 1.05 to 16.70, p = 0.04) and having any STIs (OR 2.62, 95% CI 1.01 to 6.80 p = 0.047) to be associated with detectable (>40 copies/mL) seminal plasma HIV RNA. Having chlamydia at any sites (OR 3.17, 95% CI 1.07 to 9.44, p = 0.04) was associated with detectable rectal HIV RNA. Incidences of syphilis, gonorrhoea and chlamydia were 13.4, 16.4 and 18.1 per 100 person-years respectively. Nine participants had detectable HIV RNA (five in blood, one in semen, two in rectal samples and one in both blood and rectal samples) at 12 and/or 24 months after ART. CONCLUSIONS: STIs were extremely common among HIV-positive MSM prior to and after ART. ART effectively reduced HIV RNA in all compartments. The correlation between STIs and anogenital HIV RNA, especially prior to ART and likely until complete HIV RNA suppression from ART is achieved, points to the importance of integrating asymptomatic STIs screening into Treatment as Prevention programme for MSM.