Michael Martin

Background: A recent infection testing algorithm (RITA) incorporating case surveillance (CS) with the rapid test for recent HIV infection (RTRI) was integrated into HIV testing services in Thailand as a small-scale pilot project in October 2020. Objective: We aimed to describe the lessons learned and initial outcomes obtained after the establishment of the nationwide recent HIV infection surveillance project from April through August 2022. Methods: We conducted desk reviews, developed a surveillance protocol and manual, selected sites, trained staff, implemented surveillance, and analyzed outcomes. Remnant blood specimens of consenting newly diagnosed individuals were tested using the Asanté HIV-1 Rapid Recency Assay. The duration of HIV infection was classified as RTRI-recent or RTRI-long-term. Individuals testing RTRI-recent with CD4 counts 200 cells/mm³, no opportunistic infections, and not on antiretroviral treatment were classified as RITA-CS-recent. Results: Two hundred and one hospitals in 14 high-burden HIV provinces participated in the surveillance. Of these, 69 reported ≥1 HIV diagnosis during the surveillance period. Of 1053 newly diagnosed cases, 64 (6.1%) were classified as RITA-CS-recent. On multivariate analysis, self-reporting as transgender women (adjusted odds ratio [AOR] 7.41, 95% CI 1.59‐34.53) and men who have sex with men (AOR 2.59, 95% CI 1.02‐6.56) compared to heterosexual men, and students compared to office workers or employers (AOR 3.76, 95% CI 1.25‐11.35) were associated with RITA-CS-recent infection. The proper selection of surveillance sites, utilizing existing surveillance tools and systems, and conducting frequent follow-up and supervision visits were the most commonly cited lessons learned to inform the next surveillance phase. Conclusions: Recent HIV infection surveillance can provide an understanding of current epidemiologic trends to inform HIV prevention interventions to interrupt ongoing or recent HIV transmission. The key success factors of the HIV recent infection surveillance in Thailand include a thorough review of the existing HIV testing service delivery system, a streamlined workflow, strong laboratory and health services, and regular communication between sites and the Provincial Health Offices.

The World Health Organization recommends pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV infection. The aim of this analysis is to quantify the individual risk of HIV infection over time, using a large database of high-risk individuals (n = 5583). We used data from placebo recipients in five phase III PrEP trials: iPrEx, conducted in men who have sex with men and transgender women; VOICE, conducted in young women at high sexual risk; Partners PrEP, conducted in HIV serodiscordant heterosexual couples; TDF2, conducted in high-risk heterosexual men and women; and BTS, conducted in persons who inject drugs. The probability of HIV infection over time was estimated using NONMEM7.4. We identified predictors of HIV risk and found a substantial difference in the risk of infection among and within trial populations, with each study including a mix of low, moderate, and high-risk individuals (p < 0.05). Persons who were female at birth were at a higher risk of HIV infection than people who were male at birth. Final models were integrated in a tool that can assess person-specific risk and simulate cumulative HIV risk over time. These models can be used to optimize future PrEP clinical trials by identifying potential participants at highest risk.

Background: Pre-exposure prophylaxis (PrEP) is an effective HIV prevention tool, although effectiveness is dependent upon adherence. It is important to characterize the impact of PrEP on HIV antibody responses in people who experience breakthrough infections in order to understand the potential impact on timely diagnosis and treatment. Methods: Longitudinal HIV-1-specific antibody responses were evaluated in 42 people who inject drugs (PWID) from the Bangkok Tenofovir Study (placebo=28; PrEP=14) who acquired HIV while receiving PrEP. HIV-1 antibody levels and avidity to three envelope proteins (gp41, gp160, and gp120) were measured in the plasma using a customized Bio-Plex (Bio-Rad Laboratories) assay. A survival analysis was performed for each biomarker to compare the distribution of times at which study subjects exceeded the recent/long-term assay threshold, comparing PrEP and placebo treatment groups. We fit mixed-effects models to identify longitudinal differences in antibody levels and avidity between groups. Results: Overall, longitudinal antibody levels and avidity were notably lower in the PrEP breakthrough group compared to the placebo group. Survival analyses demonstrated a difference in time to antibody reactivity between treatment groups for all Bio-Plex biomarkers. Longitudinal gp120 antibody levels within the PrEP breakthrough group were decreased compared to the placebo group. When accounting for PrEP adherence, both gp120 and gp160 antibody levels were lower in the PrEP breakthrough group compared to the placebo group. Conclusion: We demonstrate hindered envelope antibody maturation in PWID who became infected while receiving PrEP in the Bangkok Tenofovir Study, which has significant implications for HIV diagnosis. Delayed maturation of the antibody response to HIV may increase the time to detection for antibody-based tests.

Introduction: Early initiation of antiretroviral therapy (ART) can reduce HIV‐related morbidity and mortality in HIV‐positive infants. We implemented an Active Case Management Network to promote early ART initiation Aiming for Cure (ACC) in August 2014. We describe ACC implementation, early infant diagnosis (EID) coverage and ART initiation during August 2014 to July 2018 compared with a national EID survey during October 2007 to September 2011 (pre‐ACC).Methods: Thailand's 2014 HIV Treatment Guidelines recommend that HIV‐exposed infants have HIV polymerase chain reaction (PCR) testing at birth, one month and at two to four months. Testing is done at 14 national HIV PCR laboratories. When an HIV‐positive infant (HIV PCR+) is identified, PCR laboratory staff send the result to the hospital staff responsible for the infant's care and to the national laboratory case manager (CM). As part of ACC, the national laboratory CM alerts a regional CM who contacts the hospital staff caring for the infant to offer technical support with ART initiation and ART adherence. CMs enter clinical, demographic and laboratory data into the national ACC database. We analysed the ACC data from August 2014 to July 2018 to assess the ACC's impact on EID coverage, ART initiation and time‐to‐ART initiation.Results: The uptake of EID increased from 64% (pre‐ACC) to >95% in 2018 (ACC). The number of HIV‐positive infants born declined from 429 cases (pre‐ACC) to 267 cases (ACC). Median age at the first‐positive PCR declined from 75 days (pre‐ACC) to 60 days (ACC); P < 0.001. Among 429 infants diagnosed before ACC was started, 241 (56%) received ART; during ACC, 235 (88%) of 267 HIV‐positive infants received ART. The median age at ART initiation declined from 282 days before ACC to 83 days during ACC (P < 0.001) and the median time from blood collection to ART initiation declined from 168 days before ACC to 23 days during ACC (P < 0.001).Conclusions: An innovative case management network (ACC) has been established in Thailand and results suggest that the network is promoting EID and early ART initiation. The ACC model, using case‐managed PCR notification and follow‐up, may speed ART initiation in other settings.

Background Approximately 1% of adults in Thailand are infected with hepatitis C virus (HCV). New direct-acting antiviral agents achieve sustained virologic responses in >95% of HCV-infected patients and are becoming available in countries around the world. To prepare for new HCV treatment options in Thailand, this study characterized HCV infections among people who inject drugs (PWID) in Bangkok. Methods The Bangkok Tenofovir Study (BTS) was a pre-exposure prophylaxis trial conducted among PWID, 2005–2013. Blood specimens were randomly selected from PWID screened for the BTS, to test for anti-HCV antibody and HCV RNA. The HVR1 region was amplified by polymerase chain reaction, using multiplex primer sets with unique identifier sequences; amplification products were pooled in sets of 25; and consensus sequencing was performed to characterize individual HCV genotypes. Results The median age of 3679 participants tested for anti-HCV antibody was 31 years, 3016 (82.0%) were male and 447 (12.2%) were HIV infected. The prevalence of anti-HCV antibody was 44.3%. The adjusted odds of testing positive for anti-HCV antibody were higher in men (adjusted odds ratio [aOR] 3.2, 95% confidence interval [CI] 2.4–4.3), those aged 40 years or older (aOR 2.7, 95% CI 2.1–3.5), those who had more than a primary school education (aOR 1.7, 95% CI 1.4–2.1), and those who tested HIV positive (aOR 5.2, 95% CI 3.7–7.4). HCV RNA was detected in 644 (81.3%) of the 792 anti-HCV antibody-positive specimens, yielding an HCV RNA-positive prevalence of 36.0% (95% CI 33.8–38.2). Among a random sample of 249 of the 644 specimens, 218 could be characterized, and the most common HCV subtypes were 1a (30.3%), 1b (12.8%), 3a (35.8%), 3b (6.9%) and 6n (8.7%). Conclusion The prevalence of anti-HCV antibody among PWID was 44.3% and more than one third (36.0%) were HCV RNA positive. Genotypes 1, 3 and 6 accounted for all typable infections. As the government of Thailand considers introduction of direct-acting antiviral medications for people with hepatitis C, it will be important to ensure that the medications target these subtypes.

Rapid easy-to-use HIV tests offer opportunities to increase HIV testing among populations at risk of infection. We used the OraQuick Rapid HIV-1/2 antibody test (OraQuick) in the Bangkok Tenofovir Study, an HIV pre-exposure prophylaxis trial among people who inject drugs. The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial. We tested participants’ oral fluid for HIV using OraQuick monthly and blood using a nucleic-acid amplification test (NAAT) every 3 months. We used Kaplan-Meier methods to estimate the duration from a positive HIV NAAT until the mid-point between the last non-reactive and first reactive oral fluid test and proportional hazards to examine factors associated with the time until the test was reactive. We screened 3678 people for HIV using OraQuick. Among 447 with reactive results, 436 (97.5%) were confirmed HIV-infected, 10 (2.2%) HIV-uninfected, and one (0.2%) had indeterminate results. Two participants with non-reactive OraQuick results were, in fact, HIV-infected at screening yielding 99.5% sensitivity, 99.7% specificity, a 97.8% positive predictive value, and a 99.9% negative predictive value. Participants receiving tenofovir took longer to develop a reactive OraQuick (191.8 days) than participants receiving placebo (16.8 days) (p = 0.02) and participants infected with HIV CRF01_AE developed a reactive OraQuick earlier than participants infected with other subtypes (p = 0.04). The oral fluid HIV test performed well at screening, suggesting it can be used when rapid results and non-invasive tools are preferred. However, participants receiving tenofovir took longer to develop a reactive oral fluid test result than those receiving placebo. Thus, among people using pre-exposure prophylaxis, a blood-based HIV test may be an appropriate choice. ClinicalTrials.gov NCT00119106.

Objectives. We examined the causes of hospitalization and death of people who inject drugs participating in the Bangkok Tenofovir Study, an HIV preexposure prophylaxis trial.Methods. The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial conducted during 2005 to 2012 among 2413 people who inject drugs. We reviewed medical records to define the causes of hospitalization and death, examined participant characteristics and risk behaviors to determine predictors of death, and compared the participant mortality rate with the rate of the general population of Bangkok, Thailand.Results. Participants were followed an average of 4 years; 107 died: 22 (20.6%) from overdose, 13 (12.2%) from traffic accidents, and 12 (11.2%) from sepsis. In multivariable analysis, older age (40–59 years; P = .001), injecting drugs (P = .03), and injecting midazolam (P < .001) were associated with death. The standardized mortality ratio was 2.9.Conclusions. People who injected drugs were nearly 3 times as likely to die as were those in the general population of Bangkok and injecting midazolam was independently associated with death. Drug overdose and traffic accidents were the most common causes of death, and their prevention should be public health priorities.