The Impact of Accelerated ART Initiation on Adverse Outcomes and Viral Non-Suppression among People with HIV in Thailand: Empirical Evidence from an Observational Cohort Study

Aim 1. Accelerated antiretroviral therapy (ART) initiation, including starting ART on the day of HIV diagnosis, has emerged to be one of the approaches to improve ART uptake by shortening or removing some preparatory steps before ART initiation. By doing so, accelerated ART initiation is thought to remove some structural barriers associated with ART initiation process. However, several concerns still need to be addressed, such as whether the expedited process would lead to adverse treatment outcomes after ART initiation. Searched strategy was developed using both MeSH and free text terms relevant to accelerated ART initiation (same-day, immediate, rapid). Exclusion criteria were studies that did not focus on HIV, did not involve HIV treatment, included individuals with HIV aged lower than 12, and contained non-human subjects. Additionally, we excluded articles that were case-reports, qualitative studies, systematic reviews, commentary, points of view, and conference presentations. Four electronic databases (PubMed, Embase, Web of Science, MEDLINE) were used to identify relevant studies published in English between January 2015 and December 2023. Outcomes were retention, viral suppression, pre-ART screening procedures, preferred baseline antiretroviral regimens, additional baseline medications, and adverse events after ART initiation. Two independent researchers were involved in the study selection process. Of 5,455 studies retrieved, 25 studies were included in the review (Cohen’s kappa: 0.88). Six studies reported findings from randomized controlled trials conducted in Lesotho (n=2), Haiti (n=1), South Africa (n=3), and Kenya (n=1), with one study conducted in both South Africa and Keya; 19 studies were observational cohort study from Ethiopia (n=4), West Africa (n=1), Italy (n=2), the United States (n=3), South Africa (n=3), Kenya (n=1), Rwanda (n=1), Sub-Saharan African region (n=1), the United Kingdom (n=1), Turkey (n=1), and China (n=1). The majority of the studies were conducted in urban areas (n=19). Of the 25 included studies, 19 had same-day ART initiation as the intervention or the exposure (three studies measured the time to ART initiation from the day of care engagement, and 16 studies measured it from the day of HIV diagnosis). There was heterogeneity in the pre-ART screening procedures, from relying on symptomatic screening and history assessment to using non-molecular rapid tests to help identify individuals with increased risk of clinical contraindications. Despite this, individuals with symptoms consistent with WHO stage 4 neurological diseases were not eligible for ART. Efavirenz-based ARV was the most regimen reported. The majority of PWH preferred to start ART within 7 days of HIV diagnosis or care engagement (range: 56.5%-86%). Our review suggested mixed results on retention in care and viral suppression after ART initiation, although many studies indicated potential benefits. Despite this, no study reported an association between clinical adverse events, including deaths, and accelerated ART initiation. Our review suggested that accelerated ART initiation can potentially increase ART uptake while not negatively impacting treatment outcomes in some settings. New tools in HIV treatment, such as safer drug regimens and injectable ART, may help improve PWH’s experience and reduce the burden associated with pill burden and frequent clinic visits. Aim 2. Accelerated antiretroviral therapy (ART) initiation has been proposed to address some structural barriers associated with the ART initiation process and improve ART uptake. Despite this, there has yet to be a consensus on how this approach should be implemented, especially concerning the clinical readiness screening procedures. While emerging literature has reported the clinical safety of accelerated ART, limited data are reported from Thailand. Given the heterogeneity of clinical profiles of people with HIV (PWH) in different regions, past studies may not be generalizable to Thailand. Additionally, as different screening procedures affect the time to ART initiation, we need to learn how these procedures impact treatment outcomes. Data were obtained from PWH from 10 ART facilities in six provinces (Chiang Rai, Chiang Mai, Chonburi, Ubon Ratchathani, Songkhla, and Bangkok) in Thailand between July 2017 and July 2019 and followed up until January 2021. All PWH registered in HIV care were included in the analysis, regardless of baseline clinical status. ART facilities were categorized into three models according to the hospital policy on pre-ART laboratory screening procedures: Model A did not consider any lab results at the initiation, Model B considered only CD4 count, and Model C considered other non-CD4 baseline laboratory results. Log-Poisson regression was used to assess the impact of hospital policies on adverse outcomes (deaths, ART discontinuation, loss to follow-up) at months three, six, 12, 18, and 24 after care engagement. Logistic regression was used to examine the impact of hospital policies on viral non-suppression (VNS, HIV-1 RNA>50 copies/mL) at months six, 12, and 18 after ART initiation. Multilevel mixed model was used to account for potential clustering within each hospital policy. Of 10,926 PWH in the dataset, 9,695 (88.7%) were included in this study. Among these, 68% (6,571/9,695), 13% (1,236/9,695), and 19% (1,888/9,695) were in Models A, B, and C, respectively. Both Models A and B had 2 ART facilities each, while Model C had 6 ART facilities. 54.2% (5,257/9,695) self-reported to be men who have sex with men, and the overall baseline median CD4 (IQR) was 168 (129-404) cells/mm3. Compared to Model A, the average risk ratio (95%CI) of adverse events at months three, six, 12, 18, and 24 for Model B was 1.14(1.08-1.20), 1.40(1.31-1.49), 1.19(1.10-1.27), 1.11(1.02-1.21), and 1.32(1.21-1.44), respectively, while it was 1.21(1.16-1.27), 1.76(1.67-1.85), 1.59(1.50-1.67), 1.81(1.71-1.90), and 1.98(1.88-2.10) for Model C, respectively. Of 9,695 PWH, 6,785 (70%) had a confirmed date of ART initiation; 37% (2,513/6,785), 34% (2,332/6,785), and 13% (851/6,785) PWH had information on viral load status at months six, 12, and 24 after ART initiation, respectively. Among these samples, compared to Model A, the average odds ratio (95%CI) of VNS for Model B at months six, 12, and 18 was 0.79(0.59-1.06), 1.06(0.71-1.55), and 1.47(0.49-3.58), respectively, while it was 1.01(0.77-1.32), 0.68(0.40-1.09), and 0.93(0.31-2.22) for Model C, respectively. ART facilities that considered CD4 or any other non-CD4 baseline laboratory results before starting ART had, on average, a higher likelihood of adverse outcomes after the initial care engagement visit and viral non-suppression after ART initiation than ART facilities that did not consider any baseline laboratory result. Aim 3. Clinical screening and psychosocial readiness assessments prior to antiretroviral therapy (ART) initiation are imperative to ensure clinical safety and ART adherence among people with HIV (PWH). However, multiple preparation steps and long wait times associated with ART initiation can contribute to HIV care disengagement and low ART uptake. To address some of the barriers associated with lengthy assessment process, accelerated ART initiation, an approach to start ART on or near the day of HIV diagnosis, has been proposed. Despite this, concerns with the expedited preparation process remain, especially with the PWH’s readiness to have optimal HIV care adherence. This study examined the impact of time to ART initiation on adverse outcomes after care engagement and viral non-suppression (VNS) after ART initiation among PWH in Thailand. Data were obtained from PWH from 10 ART facilities in 6 provinces (Chiang Rai, Chiang Mai, Chonburi, Ubon Ratchathani, Songkhla, and Bangkok) in Thailand between July 2017 and July 2019 and followed up until January 2021. PWH who tested negative for cryptococcal antigen test at baseline and had a confirmed date of ART initiation were included in the analysis and were categorized into three groups based on the time interval between care engagement (defined as the day that PWH first registered at an ART facility) and ART initiation: (1) same day (ART initiation upon the day of care engagement or same day), (2) 1-7 days, and (3) more than 7 days. Log-Poisson regression was used to assess the impact of time to ART initiation on adverse outcomes (deaths, ART discontinuation, and loss to follow-up) at months three, six, 12, 18, and 14 after care engagement. Logistic regression was used to examine the impact of time to ART initiation on VNS (HIV-1 RNA>50 copies/mL) after ART initiation at months six, 12, and 18 after ART initiation. Age, population, hospital policy on pre-ART screening procedures, and baseline CD4 were adjusted in the final models. Of 10,926 PWH in the dataset, 5,528 (50.6%) had complete information on the date of care engagement, negative results for the cryptococcal antigen test, and the date of ART initiation. Among these, 44.23% (2,445/5,528), 38.69% (2,139/5,528), and 17.08% (944/5,528) started ART on the day of, 1-7 days from, and more than 7 days from HIV care engagement visit, respectively. The median age (IQR) was 29 (24-36) and 61% (3,387/5,528) identified themselves as men who have sex with men. The baseline median CD4 (IQR) was 283 (162-412) cells/mm3. Compared to PWH who started ART on the day of HIV care engagement visit, the average risk ratio (RR) of adverse outcomes for those who started ART between 1-7 days at months three, six, 12, 18, and 24 was 0.73(0.60-0.89), 0.66(0.55-0.79), 0.74(0.63-0.86), 0.83(0.71-0.98), and 0.84(0.70-1.01), respectively, while it was 2.27(1.91-2.71), 2.16(1.85-2.52), 1.70(1.46-1.98), 1.93(1.65-2.25), and 2.83(2.44-3.30) for those who started ART more than 7 days, respectively. In the adjusted models, the associations from both groups became statistically non-significant, except for the more than 7 days at month 24 (adjusted RR:1.08; 95%CI:1.04-1.12). Of 5,528 PWH, 29% (1,616/55,28), 36% (1,967/5,528), and 14% (795/5,528) had information on viral load status at months six, 12, and 18 after ART initiation, respectively. Among these individuals, time to ART initiation was determined to have no impact on VNS in both crude and adjusted models. Accelerated ART initiation has the potential to improve ART uptake while maintaining optimal adherence to HIV care. However, HIV programs should recognize and respond to the diversity of needs among PWH to minimize adverse outcomes following ART initiation

Traumatic Brain Injury Stimulates Neural Stem Cell Proliferation via Mammalian Target of Rapamycin Signaling Pathway Activation

Neural stem cells in the adult brain possess the ability to remain quiescent until needed in tissue homeostasis or repair. It was previously shown that traumatic brain injury (TBI) stimulated neural stem cell (NSC) proliferation in the adult hippocampus, indicating an innate repair mechanism, but it is unknown how TBI promotes NSC proliferation. In the present study, we observed dramatic activation of mammalian target of rapamycin complex 1 (mTORC1) in the hippocampus of mice with TBI from controlled cortical impact (CCI). The peak of mTORC1 activation in the hippocampal subgranular zone, where NSCs reside, is 24-48 h after trauma, correlating with the peak of TBI-enhanced NSC proliferation. By use of a Nestin-GFP transgenic mouse, in which GFP is ectopically expressed in the NSCs, we found that TBI activated mTORC1 in NSCs. With 5-bromo-2'-deoxyuridine labeling, we observed that TBI increased mTORC1 activation in proliferating NSCs. Furthermore, administration of rapamycin abolished TBI-promoted NSC proliferation. Taken together, these data indicate that mTORC1 activation is required for NSC proliferation postinjury, and thus might serve as a therapeutic target for interventions to augment neurogenesis for brain repair after TBI

mTOR SIGNALING MEDIATES TBI-ENHANCED NEURAL STEM CELL PROLIFERAION

poster abstractTraumatic Brain Injury (TBI) induced neuron death was once thought to be irreversible. However, the identification of neural stem cells (NSCs) in the adult brain holds the hope of repairing injured brain following TBI. Our pre-vious study showed that TBI promotes NSC proliferation in an attempt to ini-tial an innate repair and/or plasticity mechanisms. However, this induced proliferation is transient without significantly increasing neurogenesis. It suggests that additional intervention is required to further increase NSC pro-liferation to enhance neurogenesis for successfully repairing the damaged brain following TBI. In order to determine the molecular mechanism that mediates TBI-enhanced NSC proliferation, we assessed the activity of mam-malian target of rapamycin (mTOR) signaling by detecting the level of Phospho-S6 Ribosomal protein (pS6), an indicator of the activity of mTOR signaling. We found that the level of pS6 was transient but dramatically in-creased prior to TBI-enhanced NSC proliferation. In contrast inhibiting the activity of mTOR signaling with rapamycin attenuated this effect, indicating that mTOR signaling mediates TBI-enhanced NSC proliferation. Further stimulating mTOR signaling strengthened the effect of TBI-enhanced NSC proliferation. These results suggest that mTOR signaling mediates TBI-enhanced neural stem cell proliferation and stimulating mTOR signaling may be a potential therapeutic approach to enhance neurogenesis for post-traumatic functional recovery

Prevalence and the associated factors of hepatitis B and hepatitis C viral infections among HIV-positive individuals in same-day antiretroviral therapy initiation program in Bangkok, Thailand

Background Viral hepatitis is highly prevalent among people with HIV (PWH) and can lead to chronic liver complications. Thailand started universal hepatitis B vaccination at birth in 1992 and achieved over 95% coverage in 1999. We explored the prevalence of hepatitis B and C viral infections and the associated factors among PWH from same-day antiretroviral therapy (SDART) service at the Thai Red Cross Anonymous Clinic, Bangkok, Thailand. Methods We collected baseline characteristics from PWH enrolled in the SDART service between July 2017 and November 2019. Multivariable logistic regression was performed to determine factors associated with positive hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV). Results A total of 4011 newly diagnosed PWH who had HBsAg or anti-HCV results at baseline: 2941 men who have sex with men (MSM; 73.3%), 851 heterosexuals (21.2%), 215 transgender women (TGW; 5.4%), and 4 transgender men (0.1%). Median age was 27 years. Overall seroprevalence of HBsAg and anti-HCV were 6.0 and 4.1%, respectively. Subgroup prevalence were 6.2 and 4.7% among MSM, 4.6 and 2.4% among heterosexuals, and 9.3 and 3.7% among TGW, respectively. Factors associated with HBsAg positivity were being MSM, TGW, born before 1992, CD4 count  30 years, alanine aminotransferase ≥ 62.5 U/L, creatinine clearance < 60 ml/min, and syphilis infection. Conclusions Around 5–10% of newly diagnosed PWH in Bangkok had hepatitis B viral infection after 25 years of universal vaccination. Anti-HCV positivity was found in 4–5% of PWH who were MSM and TGW. As World Health Organization and Thailand national guidelines already support routine screening of hepatitis B and C viral infections in PWH and populations at increased risk of HIV including MSM and TGW, healthcare providers should reinforce this strategy and provide linkage to appropriate prevention and treatment interventions. Catch-up hepatitis B vaccination should be made available under national health coverage

Barriers and facilitators of HIV vaccine and prevention study participation among Young Black MSM and transwomen in New York City

<div><p>Background</p><p>Black men who have sex with men (MSM), and Transwomen (TW) shoulder disproportionate burden of HIV. However, they are unrepresented in HIV vaccine trials. We investigated the perceptions of that factors associated with HIV vaccine trials participation among Black MSM and TW in New York.</p><p>Methods</p><p>Self-administered online questionnaires were administered to 18–29 years of NYC residents who identified as Black MSM and TW, assessing demographics, awareness and willingness to participate in HIV vaccine trials, barriers and facilitators associated with willingness, and sexual behaviors. Frequency summation was performed to determine barriers and facilitators, and logistic regression analysis was performed to determine factors association with expressed willingness.</p><p>Results</p><p>Black MSM and TW who reported engaging in risk behaviors had a 61% lower likelihood of participating in HIV vaccine trials when compared to those who did not report engaging in any risk behavior. Facilitators associated with trial participation were: cash compensation, confidentiality regarding participation, public transportation vouchers, gift cards, and food or grocery vouchers as potential facilitators for trial participation. Conversely, fear of side effects from the vaccine, concerns about testing positive on routine HIV testing due to an HIV vaccine, limited knowledge of research trials, and fear of being judged as HIV-positive were perceived as barriers.</p><p>Conclusions</p><p>These findings provided insights into the considerations and perceptions of Black MSM and TW towards HIV vaccine trials. However, further studies are needed to delineate the complex mechanisms underlying the decision-making process and establish approaches to increase study participation in this population.</p></div

Barriers and facilitators to HIV vaccine trial participation (N = 189).

<p>Barriers and facilitators to HIV vaccine trial participation (N = 189).</p

Sexual patterns and practices among men who have sex with men and transgender women in Thailand: A qualitative assessment.

The global trend in HIV incidence overall is declining; however, there is a plateau in new HIV infection among men who have sex with men (MSM) and transgender women (TGW) despite extensive investment in HIV prevention targeting these populations. Many studies usually conflate these two groups together, which may overlook many disparate characteristics unique to each population, impeding the efficacy of HIV interventions. To better understand the vulnerable diversity that may put these individuals at risk of HIV infection, we conducted qualitative analysis among Thai MSM and TGW, aiming to identify sexual pattern themes of MSM and TGW in Bangkok in order to better understand their distinctive sexual life context. Convenient and purposive samplings were used to recruit Thai MSM and TGW aged ≥ 18 years old and living in Bangkok, Thailand, for focused group discussions and one-on-one in-depth interviews, respectively. Total of 12 MSM and 13 TGW participated in focused group discussions, which were conducted separately for MSM and TGW. Additionally, 5 MSM and 5 TGW were involved in one-on-one in-depth interviews. Thematic analyses were performed separately for MSM and TGW. The results show that MSM and TGW have distinct and diverse sexual patterns, and within the identified themes: partnering, partner finding, protection, and enhancing sexual pleasure (only for MSM). Participants reported having varying sexual experiences. Recognizing the difference and diversity in partnering and sexual practice of MSM and TGW is crucial in order to develop tailored interventions that suit the vulnerability of the key populations in Thailand

Sociodemographics, risk behaviors and past research experience (N = 189).

<p>Sociodemographics, risk behaviors and past research experience (N = 189).</p

Knowledge and awareness of HIV vaccine and other biomedical prevention trials.

<p>Knowledge and awareness of HIV vaccine and other biomedical prevention trials.</p

Factors associated with Willingness to participate in HIV vaccine trials among those who have not participated in HIV vaccine trials in the past (N = 189) and multivariable logistic regression examining the association between willingness to participate in HIV vaccine trials and sociodemographic characteristics and risk score (N = 155).

<p>Factors associated with Willingness to participate in HIV vaccine trials among those who have not participated in HIV vaccine trials in the past (N = 189) and multivariable logistic regression examining the association between willingness to participate in HIV vaccine trials and sociodemographic characteristics and risk score (N = 155).</p