High mortality in adolescents and young adults with perinatally-acquired HIV in Thailand during the transition to adulthood.

Transitioning from pediatric to adult care remains a challenge for adolescents and young adults with perinatally-acquired HIV (AYA-PHIV). We assessed treatment outcomes and mortality among Thai AYA-PHIV. The study included AYA-PHIV who reached age 18-24 years who started antiretroviral treatment during childhood at five pediatric HIV clinics across Thailand. From November 2020-July 2021, data were gathered from a cohort database, medical records, and the Thai National AIDS Program. Of 811 eligible AYA-PHIV, 93% were alive; median age 22.3 years (IQR 20.6-23.7), treatment duration 16.1 years (IQR 13.4-18.0). Current HIV care was provided in adults (71%) and pediatric clinics (29%). Treatment regimens included non-nucleoside reverse transcriptase inhibitors (55%), protease inhibitors (36%), and integrase inhibitors (8%); 78% had HIV RNA <200 copies/ml. Of the 7.0% who died, median age at death was 20.8 years (IQR 20.6-22.1); 88% were AIDS-related death. Mortality after age 18 was 1.76 per 100-person years (95% confidence interval 1.36-2.28). Those with CD4 <200 cell/mm3 at age 15 had higher risk of mortality (adjusted hazard ratio 6.16, 95% CI 2.37-16.02). In conclusion, the high mortality among Thai AYA-PHIV indicated the need for better systems to support AYA-PHIV during the transition to adulthood.

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.

Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies.

BACKGROUND: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized. METHODS: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. RESULTS: Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection. CONCLUSIONS: This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.

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 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.

Adherence to antiretroviral therapy, stigma and behavioral risk factors in HIV-infected adolescents in Asia.

We studied behavioral risks among HIV-infected and uninfected adolescents using an audio computer-assisted self-interview. A prospective cohort study was initiated between 2013 and 2014 in Malaysia, Thailand, and Vietnam. HIV-infected adolescents were matched to uninfected adolescents (4:1) by sex and age group (12-14 and 15-18 years). We enrolled 250 HIV-infected (48% male; median age 14.5 years; 93% perinatally infected) and 59 uninfected (51% male; median age 14.1 years) adolescents. At enrollment, HIV-infected adolescents were on antiretroviral therapy (ART) for a median (IQR) of 7.5 (4.7-10.2) years, and 14% had HIV-RNA >1000 copies/mL; 19% reported adherence <80%. Eighty-four (34%) HIV-infected and 26 (44%) uninfected adolescents reported having ever smoked cigarettes or drunk alcohol (p = 0.13); 10% of HIV-infected and 17% of uninfected adolescents reported having initiated sexual activity; 6 of the HIV-infected adolescents had HIV-RNA >1000 copies/mL. Risk behaviors were common among adolescents, with few differences between those with and without HIV.

Attrition and Mortality of Children Receiving Antiretroviral Treatment through the Universal Coverage Health Program in Thailand.

OBJECTIVE: To assess mortality and loss to follow-up of children with HIV infection who started antiretroviral therapy (ART) through the Universal Coverage Health Program (UC) in Thailand. STUDY DESIGN: Children with HIV infection who initiated ART at age <15 years through the UC between 2008 and 2013 were included in the analysis. Death was ascertained through linkage with the National Death Registry. A competing-risks method was used to calculate subdistribution hazard ratios (SHRs) of predictors for loss to follow-up. Death was considered a competing risk. Cox proportional hazards models were used to assess predictors of mortality. RESULTS: A total of 4618 children from 497 hospitals in Thailand were included in the study. Median age at ART initiation was 9 years (IQR, 6-12 years), and the median duration of tracking was 4.1 years (a total of 18 817 person-years). Three hundred and ninety-five children (9%) died, for a mortality rate of 2.1 (95% CI, 1.9-2.3) per 100 person-years, and 525 children (11%) were lost to follow-up, for a lost to follow-up rate of 2.9 (95% CI, 2.7-3.2) per 100 person-years. The cumulative incidence of loss to follow-up increased from 4% at 1 year to 8.8% at 3 years. Children who started ART at age ≥12 years were at the greatest risk of loss to follow-up. The probability of death was 3.2% at 6 months and 6.4% at 3 years. Age ≥12 years at ART initiation, lower baseline CD4%, advanced HIV staging, and loss to follow-up were associated with mortality. CONCLUSION: The Thai national HIV treatment program has been very effective in treating children with HIV infection, with low mortality and modest rates of loss to follow-up.

Long-term outcomes of rapid antiretroviral NNRTI-based initiation among Thai youth living with HIV: a national registry database study.

INTRODUCTION: The Thai National AIDS programme (NAP) treatment guidelines have recommended rapid antiretroviral therapy (ART) initiation, regardless of CD4 count since 2014. We assessed treatment outcomes among youth living with HIV (YLHIV), initiating first-line ART and assessed the association between virological failure (VF) and timing of ART initiation. METHODS: We retrospectively reviewed data for YLHIV aged 15-24 years, initiating non-nucleoside reverse transcriptase inhibitor-based ART from 2014 to 2019, through the NAP database. We classified the timing of ART into three groups based on duration from HIV-positive diagnosis or system registration to ART initiation: (1) <1 month (rapid ART); (2) 1-3 months (intermediate ART); and (3) >3 months (delayed ART). VF was defined as viral load (VL) ≥ 1000 copies/ml after at least 6 months of first-line ART. Factors associated with VF were analysed using generalized estimating equations. RESULTS: Of 19,825 YLHIV who started ART, 78% were male. Median (interquartile range, IQR) age was 21 (20-23) years and CD4 count was 338 (187-498) cells/mm3 . After registration, 12,216 (62%) started rapid ART, 4272 (22%) intermediate ART and 3337 (17%) delayed ART. The proportion of YLHIV starting ART <30 days significantly increased from 43% to 57% from 2014-2016 to 2017-2019 (p < 0.001). The median duration of first-line therapy was 2 (IQR 1-3) years and 89% started with efavirenz-based regimens. Attrition outcomes showed that 325 (2%) died (0.73 [95% CI 0.65-0.81] per 100 person-years [PY]) and 1762 (9%) were loss to follow-up (3.96 [95% CI 3.78-4.15] per 100 PY). Of 17,512 (88%) who had VL checked from 6 to 12 months after starting treatment, 80% achieved VL <200 copies/ml. Overall, 2512 experienced VF 5.87 (95% CI 5.65-6.11) per 100 PY). In a multivariate model, the adjusted incidence rate ratio for VF was 1.47 (95% CI 1.33-1.63, p < 0.001) in the delayed ART group and 1.14 (95% CI 1.03-1.25, p< 0.001) in the intermediate ART group, compared to YLHIV in the rapid ART group. CONCLUSIONS: Rapid ART initiation after diagnosis was associated with significantly reduced risks of VF and death in YLHIV, supporting the implementation of rapid ART for optimizing health outcomes.

Treatment Outcomes After Switching to Second-Line Anti-Retroviral Therapy: Results From the Thai National Treatment Program.

This study aimed to assess second-line antiretroviral therapy (ART) outcomes in a National HIV Treatment program. People living with HIV aged ≥18 years initiating first-line ART who switched to second-line protease inhibitor-based regimens from January 2008 to May 2019, with a minimum of 1-year follow-up were studied. The primary outcome was second-line treatment failure (two consecutive virological failure episodes (viral load ≥1000 copies/mL)). Of 318,506 PLH initiating ART, 29,015 (9.1%) switched to second-line regimens after a median (IQR) ART duration of 1.63 (0.60-3.59) years. Lost to follow-up (LTFU) occurred in 5316 (18.3%) of whom 1376 (5%) remained LTFU and alive; 4606 (15.9%) died. Cumulative second-line failure incidence was 9.8% at 6 years, more common in females, younger PLH those with lower switch CD4 cell counts. Multidisciplinary, innovative support systems are needed to improve second-line treatment outcomes, particularly those relating to modifiable risk factors.

Outcomes after switching to second line antiretroviral regimens in the Thai National Treatment programWe assessed the rates of virological failure, losses to follow-up and death in 29,015 people who switched to second line antiretroviral therapy in Thailand. The cumulative rate of virological failure was a 9.8% at 6 years, loss to follow-up occurred in 18.3% (5% who remained alive) and 15.9% died. Women and those with lower CD4 counts at switch had the highest risk of virological failure.

Factors Associated with Morbidity and Mortality Among Sexually Active Asian Adolescents and Young Adults with Perinatally Acquired HIV.

We assessed morbidity and mortality among Thai and Vietnamese adolescents and young adults with perinatally acquired human immunodeficiency virus (PHIV) compared with matched HIV-negative peers, 12-24 years of age. Data on serious adverse events (SAEs) were prospectively collected between 2013 and 2018 according to U.S. NIH Division of AIDS criteria. Of 288 youth, 142 had PHIV and 146 were HIV negative. At enrollment, the overall median age was 19 (interquartile range [IQR] 17-20) years, 67% were female, and 95% were Thai. Almost all PHIV youth (99%) were receiving antiretroviral therapy; 50% self-reported adherence ≥95%. Median CD4 was 579 (IQR 404-800) cells/mm3, and 24% had HIV-RNA ≥1,000 copies/mL. During follow-up, 31 (22%) PHIV youth and 9 (6%) HIV-negative youth had at least one SAE. The overall crude SAE rate was 4.66 (3.42-6.35) per 100 person-years (PY); 7.22 (5.08-10.26) per 100 PY among youth with PHIV and 2.10 (1.09-4.03) per 100 PY in HIV-negative youth (p < .001). All seven deaths that occurred were among those with PHIV and primarily due to opportunistic infections (e.g., pneumocystis pneumonia, tuberculous meningitis). In multivariate analyses, having PHIV, being <20 years of age, and having anogenital high-risk human papillomavirus (HPV) infection with types 16 and/or 18 increased risk of SAEs. Among PHIV youth, CD4 count <350 cells/mm3, HIV-RNA ≥1,000 copies/mL, advanced WHO stages, and having anogenital HPV 16 and/or 18 infection predicted higher incidence of SAEs; no prior use of alcohol was protective. These data emphasize the need for tailored interventions for adolescents with PHIV to prevent long-term morbidity and mortality.

Virological failure and treatment switch after ART initiation among people living with HIV with and without routine viral load monitoring in Asia.

INTRODUCTION: Viral load (VL) testing is still challenging to monitor treatment responses of antiretroviral therapy (ART) for HIV treatment programme in Asia. We assessed the association between routine VL testing and virological failure (VF) and determine factors associated with switching to second-line regimen. METHODS: Among 21 sites from the TREAT Asia HIV Observational Database (TAHOD), people living with HIV (PLHIV) aged ≥18 years initiating ART from 2003 to 2021 were included. We calculated the average number of VL tests per patient per year between the date of ART initiation and the most recent visit. If the median average number of VL tests was ≥ 0.80 per patient per year, the site was classified as a routine VL site. A site with a median < 0.80 was classified into the non-routine VL sites. VF was defined as VL ≥1000 copies/ml during first-line therapy. Factors associated with VF were analysed using generalized estimating equations with Poisson distribution. RESULTS: Of 6277 PLHIV starting ART after 2003, 3030 (48%) were from 11 routine VL testing sites and 3247 (52%) were from 10 non-routine VL testing sites. The median follow-up was 9 years (IQR 5-13). The median age was 35 (30-42) years; 68% were male and 5729 (91%) started non-nucleoside reverse-transcriptase inhibitor-based regimen. The median pre-ART CD4 count in PLHIV from routine VL sites was lower compared to non-routine VL sites (144 vs. 156 cells/mm3 , p <0.001). Overall, 1021 subsequent VF at a rate of 2.15 (95% CI 2.02-2.29) per 100 person-years (PY). VF was more frequent at non-routine VL sites (adjusted incidence rate ratio 2.85 [95% CI 2.27-3.59]) compared to routine VL sites. Other factors associated with an increased rate of VF were age <50 years and CD4 count <350 cells/mm3 . A total of 817 (13%) patients switched to second-line regimen at a rate of 1.44 (95% CI 1.35-1.54) per 100 PY. PLHIV at routine VL monitoring sites were at higher risk of switching than those at non-routine VL sites (adjusted sub-hazard ratio 1.78 95% CI [1.17-2.71]). CONCLUSIONS: PLHIV from non-routine VL sites had a higher incidence of persistent VF and a low switching regimen rate, reflecting possible under-utilized VL testing.

Clinical outcomes of pediatric COVID-19 in a tertiary care center in Bangkok, Thailand.

Objective: To describe the clinical characteristics and outcomes of pediatric COVID-19 in Thailand, where favipiravir is the mainstay of antiviral treatment. Methods: We conducted a hospital based observational cohort study of COVID-19 among children. The study included children (age <15 years) with confirmed positive reverse transcriptase-polymerase chain reaction for SARS-CoV-2 from nasopharyngeal swab. Results: From April to July 2021, 416 cases with a median age of 7.1 (interquartile range 2.7-11.6) years were included in the study. The spectrum of disease included 82 (20%) asymptomatic, 232 (56%) mild and 102 (24%) with pneumonia. Abnormal chest x-ray findings included ground-glass opacities (46%), focal infiltrations (27%), perihilar opacities (19%), reticular infiltrations (15%) and other non-specific findings (4%). Only 12 children (3%) required oxygen support. Favipiravir was prescribed to 129 children (31%); 102 patients with pneumonia and 27 patients at risk for disease progression. Pneumonia was more common in age <3 years compared with those aged 3-<12 years (adjusted odds ratio (aOR) 0.30, 95% CI 0.17-0.52), 12-15 years (aOR 0.40, 95% CI 0.21-0.77) and in patients with comorbidities (aOR 2.36, 95% CI 1.09-5.12). Conclusions: One-fourth of pediatric COVID-19 patients had pneumonia, but few required oxygen support. Off-label use of Favipiravir in pediatric COVID-19 patients in a recent outbreak in Bangkok is reported.

Rapid antiretroviral initiation among Thai youth living with HIV in the National AIDS programme in the era of treatment at any CD4 cell count: a national registry database study.

INTRODUCTION: The process indicators of ending the HIV epidemic include 90% of people living with HIV receiving antiretroviral therapy (ART). The population of youth, however, has less access to healthcare. We assessed ART initiation and attrition outcomes of the HIV continuum from HIV diagnosis to ART initiation in youth living with HIV (YLHIV) and factors associated with ART initiation. METHODS: We studied YLHIV aged 15 to 24 years who were registered on the National AIDS Program (NAP) from January 2008 to May 2019. The study period was divided into 2008 to 2013 (initiated ART by CD4-guided criteria) and 2014 to 2018 (initiate ART at any CD4). Date of registration was used as a surrogate for the diagnosis date and defined as the baseline. The database included ART prescription and laboratory results, and the vital status was linked daily with the National Death Registry. Competing risk methods were used to assess factors associated with accessing ART, with loss to follow-up (LTFU) and death considered as competing events. Logistic regression was used to assess factors associated with rapid ART initiation, defined as initiation ≤1 month after registration. RESULTS: Overall, 51,607 youth registered on the NAP (42% between 2008 and 2013). Median age was 21 (IQR 20 to 23) years; 64% were male. Overall ART initiation was 80% in the first period and 83% in the second. The ART initiation rate was higher among YLHIV aged 15 to 19 years (86%) than 20 to 24 years (82%) (p < 0.001) in the second period. The proportion of youth starting rapid ART increased significantly from 27% to 52% between the two periods (p < 0.001). Factors associated with ART initiation were age 15 to 19 years (aSHR 1.09, 95% CI 1.06 to 1.11), female (aSHR 1.26, 95% CI 1.23 to 1.29) and registration year 2014 to 2018 (aSHR 1.73, 95% CI 1.69 to 1.76). The cumulative incidence of LTFU/death prior to ART initiation at 12 months was 3.8% (95% CI 3.6% to 4.1%) in the first period and 1.9% (95% CI 1.8% to 2.1%) in the second period. CONCLUSIONS: In the era of universal treatment of all at any CD4 level, 83% of YLHIV registered on the Thai National AIDS Program initiated ART. The majority initiated within one month of registration.

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.

Impact of low-level viraemia on virological failure among Asian children with perinatally acquired HIV on first-line combination antiretroviral treatment: a multicentre, retrospective cohort study.

INTRODUCTION: The clinical relevance of low-level viraemia (LLV) and virological outcomes among children living with HIV (CLHIV) remains controversial. This study aimed to determine the impact of LLV on virological failure (VF) among Asian CLHIV on first-line combination antiretroviral therapy (cART). METHODS: CLHIV aged <18 years, who were on first-line cART for ≥12 months, and had virological suppression (two consecutive plasma viral load [pVL] <50 copies/mL) were included. Those who started treatment with mono/dual antiretroviral therapy, had a history of treatment interruption >14 days, or received treatment and care at sites with a pVL lower limit of detection >50 copies/mL were excluded. LLV was defined as a pVL 50 to 1000 copies/mL, and VF as a single pVL >1000 copies/mL. Baseline was the time of the second pVL < 50 copies/mL. Cox proportional hazards models were performed to assess the association between LLV and VF. RESULTS: From January 2008 to September 2016, 508 CLHIV (55% female) were eligible for the study. At baseline, the median age was 9.6 (IQR: 7.0 to 12.3) years, cART duration was 1.4 (IQR: 1.3 to 1.8) years, 97% of CLHIV were on non-nucleoside reverse transcriptase inhibitor-based regimens, and the median CD4 was 25% (IQR: 20% to 30%). Over a median follow-up time of 6.0 (IQR: 3.1 to 8.9) years from baseline, 86 CLHIV (17%) had ever experienced LLV, of whom 32 (37%) had multiple LLV episodes. Female sex, living in Malaysia (compared to Cambodia), having family members other than biological parents/grandparents as a primary caregiver, and baseline CD4 < 25% increased risk of LLV. Overall, 115 children (23%) developed VF, corresponding to a rate of 4.0 (95%CI: 3.4 to 4.9) per 100 person-years of follow-up (PYFU). VF was greater among children who had ever experienced LLV compared with those who maintained virological suppression throughout the study period (8.9 vs. 3.3 per 100 PYFU; p < 0.001). In multivariable analyses, ever experiencing LLV was associated with increased risk of subsequent VF (adjusted hazard ratio: 3.01; 95%CI: 1.97 to 4.60). CONCLUSIONS: LLV increased the risk of subsequent VF among Asian CLHIV who had previously been suppressed on first-line cART. Adherence interventions and additional targeted pVL monitoring may be warranted among children with LLV to facilitate early detection of VF.

Determinants of Viral Resuppression or Persistent Virologic Failure After Initial Failure With Second-Line Antiretroviral Treatment Among Asian Children and Adolescents With HIV.

Of 56 children with perinatally acquired human immunodeficiency virus (HIV) who had been prescribed second-line protease inhibitor-based antiretroviral therapy and had ≥1 previous episode of viral failure (HIV RNA, ≥1000 copies/mL), 46% had ≥1, 34% had ≥2, and 23% had ≥3 consecutive episodes of viral failure during the 2 years of follow-up. Two of these children experienced a major protease inhibitor mutation.

Peritransition Outcomes of Southeast Asian Adolescents and Young Adults With HIV Transferring From Pediatric to Adult Care.

PURPOSE: The aim of this article was to study the clinical and social outcomes of health care transition among Asian adolescents and young adults with HIV (AYHIV). METHODS: AYHIV who transferred from a pediatric to an adult clinic within the past year across five sites in Malaysia, Thailand, and Vietnam had clinical and laboratory evaluations and completed questionnaires about their health, socioeconomic factors, and transition experiences. Multiple logistic regression was used to assess associations with HIV viremia. RESULTS: Of 93 AYHIV enrolled between June 2016 and April 2017, 56% were female, 87% acquired HIV through perinatal exposure, median age was 20 years (interquartile range [IQR] 18.5-21). Two-thirds were in a formal education program, 43% were employed, 43% of females and 35% of males were sexually active. Median lifetime antiretroviral therapy duration was 6.2 years (IQR 3.3-10.7); 45% had received second-line therapy. Median CD4 was 601 cells/mm3 (IQR 477-800); 82% had HIV-RNA <40 copies/mL. Being in a relationship, a shorter posttransition duration, self-reported adherence of ≥95%, and higher CD4 were inversely associated with HIV viremia. Half felt very prepared for the transfer to adult care, and 20% frequently and 43% sometimes still met with pediatric providers. Two-thirds reported needing to keep their HIV a secret, and 23%-38% reported never or rarely having someone to discuss problems with. CONCLUSIONS: Asian AYHIV in our cohort were concerned about the negative social impact of having and disclosing HIV, and one-third lacked people they could trust with their personal problems, which could have negative implications for their ability to navigate adult life.

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.

Attrition and treatment outcomes among adolescents and youths living with HIV in the Thai National AIDS Program.

BACKGROUND: There are limited data describing the care outcome of youth living with HIV in Asia. We assessed attrition and treatment outcomes among youths with behaviourly acquired HIV (BIY) and adolescents with perinatally acquired HIV (PIY) who initiated antiretroviral treatment (ART) through the National AIDS Program (NAP) in Thailand. METHODS: People living with HIV aged 10-24 years who initiated antiretroviral therapy (ART) from 2008 to 2013 through the Thai NAP and who were followed up until 2014 were included in the analysis. We assessed youths initiating ART: BIY aged 15-19 years (BIY1) and BIY aged 20-24 (BIY2) compared against PIY aged 10-14 years. Attrition rates (mortality and loss to follow-up [LTFU]) were calculated and potential associations were assessed using Cox regression. Logistic regression was used to assess associations with treatment failure. RESULTS: Of 11,954 individuals, 9909 (83%) were BIY with a median follow-up of 2.1 years and 17% were PIY with 4.2 years of follow-up. The median baseline CD4 cell count in BIY was higher (190 vs 154 cells/mm3) compared to PIY. Mortality rates were not significantly different among PIY (2.5 per 100 person years [PY], BIY1 3.1/100 PY and BIY2 2.9/100 PY, P=0.46). Compared to PIY with a crude LTFU rate of 2.9/100 PY, LTFU was higher in BIY1 (13.9/100 PY) and BIY2 (9.5/100 PY), P<0.001 and P<0.001, respectively. At 1 year after initiating ART, 16% experienced virological failure (viral load above 1000 copies/mL). Combined treatment failure and LTFU rates at 1 year after ART were higher among BIY1 (45.0%) and BIY2 (34.4%) compared to PIY (29.9%), P<0.001 and 0.001, respectively. CONCLUSION: Youth with behaviourally acquired HIV aged 15-19 years had poorer retention rates than older BIY and PIY. Targeted interventions for youth are urgently needed to improve overall treatment outcomes.

A Longitudinal Study of Behavioral Risk, Adherence, and Virologic Control in Adolescents Living With HIV in Asia.

BACKGROUND: Adolescents living with HIV (ALHIV) have poorer adherence and clinical outcomes than adults. We conducted a study to assess behavioral risks and antiretroviral therapy outcomes among ALHIV in Asia. METHODS: A prospective cohort study among ALHIV and matched HIV-uninfected controls aged 12-18 years was conducted at 9 sites in Malaysia, Thailand, and Vietnam from July 2013 to March 2017. Participants completed an audio computer-assisted self-interview at weeks 0, 48, 96, and 144. Virologic failure (VF) was defined as ≥1 viral load (VL) measurement >1000 copies/mL. Generalized estimating equations were used to identify predictors for VF. RESULTS: Of 250 ALHIV and 59 HIV-uninfected controls, 58% were Thai and 51% females. The median age was 14 years at enrollment; 93% of ALHIV were perinatally infected. At week 144, 66% of ALHIV were orphans vs. 28% of controls (P < 0.01); similar proportions of ALHIV and controls drank alcohol (58% vs. 65%), used inhalants (1% vs. 2%), had been sexually active (31% vs. 21%), and consistently used condoms (42% vs. 44%). Of the 73% of ALHIV with week 144 VL testing, median log VL was 1.60 (interquartile range 1.30-1.70) and 19% had VF. Over 70% of ALHIV had not disclosed their HIV status. Self-reported adherence ≥95% was 60% at week 144. Smoking cigarettes, >1 sexual partner, and living with nonparent relatives, a partner or alone, were associated with VF at any time. CONCLUSIONS: The subset of ALHIV with poorer adherence and VF require comprehensive interventions that address sexual risk, substance use, and HIV-status disclosure.