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HIV-associated neurocognitive disorder (HAND) remains a challenge despite antiretroviral therapy (ART), and has been linked to monocyte/macrophage (M/M) migration to the brain. Due to the potential impact of T cell effector mechanisms in eliminating activated/HIV-infected M/M, T cell activation may play a role in the development of HAND. We sought to investigate the relationship between cognition and both CD8+ T cell activation (HLA-DR+/CD38+) and HIV-specific CD8+ T cell responses at the time of HIV diagnosis and 12 months postinitiation of ART. CD8+ T cell activation was increased in HAND compared to cognitive normal (NL) individuals and correlated directly with plasma viral load and inversely with the cognitive status. In addition, Gag-specific cytolytic activity (CD107a/b+) was decreased in HAND compared with NL individuals and correlated with their neurological testing, suggesting a potential role of cytotoxic CD8+ T cells in the mechanism of HAND development.

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

This observational study of 123 Thai participants sought to determine the rate and severity of affective symptoms during acute HIV infection (AHI) and possible associations to disease mechanisms. At diagnosis, just prior to starting combination antiretroviral therapy (cART), AHI participants completed assessments of depression and anxiety symptoms that were repeated at 4, 12, and 24 weeks. Blood markers of HIV infection and immune activation were measured at study entry, with optional cerebrospinal fluid measures. A high frequency of participants reported symptoms that exceeded published thresholds supportive of depression (55.0%) and anxiety (65.8%) at diagnosis, with significant reductions after starting cART. Meeting a threshold for clinically relevant depressive symptoms at study entry was associated with higher baseline plasma HIV RNA (5.98 vs. 5.50, t = 2.46, p = 0.015), lower CD4 counts (328 vs. 436 cells/mm3, t = 3.46, p = 0.001), and higher plasma neopterin, a marker of macrophage activation (2694 vs. 1730 pg/mL, Mann-Whitney U = 152.5, p = 0.011). Controlling for plasma HIV RNA and CD4 count, higher baseline plasma neopterin correlated with worse initial depression and anxiety scores. Depression and anxiety symptoms are frequent in acute HIV infection, associate with plasma immune activation, and can improve concurrent with cART.

Introduction Dolutegravir (DTG) is recommended as part of first‐line antiretroviral therapy (ART) for people living with HIV(PLHIV). We sought to determine the rate of adverse events (AEs) and discontinuations among Thais treated during acute HIV infection (AHI) and switched to DTG‐based regimens. Methods Thai participants in the SEARCH010/RV254 cohort who initiated ART during AHI and switched to DTG for at least 48 weeks were prospectively observed and included in the analysis. Rates and characteristics of DTG‐related AEs and discontinuations were described. Results A total of 313 Thai participants were included in the analysis. The median age was 29 years, 96% were male, 64% had a Bachelor's degree or higher and 16% had a body mass index (BMI)

BACKGROUND: Central nervous system (CNS) infiltration by CD8+ T cells is associated with neuroinflammation in many neurodegenerative diseases, including HIV-associated dementia. However, the role of CD8+ T cells in the CNS during acute HIV infection (AHI) is unknown. METHODS: We analyzed the phenotype, gene expression, T cell receptor (TCR) repertoire, and HIV specificity of CD8+ T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of AHI (n = 26), chronic (n = 23), and uninfected (n = 8). RESULTS: CSF CD8+ T cells were elevated in AHI compared with uninfected controls. The frequency of activated CSF CD8+ T cells positively correlated to CSF HIV RNA and to markers of CNS inflammation. In contrast, activated CSF CD8+ T cells during chronic HIV infection were associated with markers of neurological injury and microglial activation. CSF CD8+ T cells in AHI exhibited increased functional gene expression profiles associated with CD8+ T cells effector function, proliferation, and TCR signaling, a unique restricted TCR Vbeta repertoire and contained HIV-specific CD8+ T cells directed to unique HIV epitopes compared with the periphery. CONCLUSIONS: These results suggest that CSF CD8+ T cells in AHI expanding in the CNS are functional and directed against HIV antigens. These cells could thus play a beneficial role protective of injury seen in chronic HIV infection if combination antiretroviral therapy is initiated early.

Introduction : The extent of viral replication during acute HIV infection (AHI) influences HIV disease progression. However, information comparing viral load (VL) kinetics with and without antiretroviral therapy (ART) in AHI is limited. The knowledge gained could inform preventive strategies aimed at reducing VL during AHI and therapeutic strategies to alter the viral kinetics that may enhance the likelihood of achieving HIV remission. Methods : The analysis utilized VL data captured during the first year of HIV infection from two studies in Thailand: the RV217 study (untreated AHI, 30 participants and 412 visits) and the RV254 study (treated AHI, 235 participants and 2803 visits). Fiebig stages were I/II (HIV RNA+, HIV IgM−) and Fiebig III/IV (HIV IgM+, Western blot-/indeterminate). Data were modelled utilizing spline effects within a linear mixed model, with a random intercept and slope to allow for between-subject variability and adjustment for the differences in variability between studies. The number of knots in the quadratic spline basis functions was determined by comparing models with differing numbers of knots via the Akaike Information Criterion. Models were fit using PROC GLIMMIX in SAS v9.3. Results : At enrolment, there were 24 Fiebig I/II and 6 Fiebig III/IV individuals in the untreated group and 137 Fiebig I/II and 98 Fiebig III/IV individuals in the treated group. Overall, the median age was 27.5 years old, most were male (89%), and CRF01_AE was the most common HIV clade (76%). By day 12 (4 days after ART in RV254), the untreated group had a 2.7-fold higher predicted mean VL level compared to those treated (predicted log VL 6.19 for RV217 and 5.76 for RV254, p = 0.05). These differences increased to 135-fold by day 30 (predicted log VL 4.89 for RV217 and 2.76 for RV254) and 1148-fold by day 120 (predicted log VL 4.68 for RV217 and 1.63 for RV254) ( p < 0.0001 for both) until both curves were similarly flat at about day 150 ( p = 0.17 between days 150 and 160). The VL trajectories were significantly different between Fiebig I/II and Fiebig III/IV participants when comparing the two groups and within the treated group ( p < 0.001 for both). Conclusions : Initiating ART in AHI dramatically changed the trajectory of VL very early in the course of infection that could have implications for reducing transmission potential and enhancing responses to future HIV remission strategies. There is an urgency of initiating ART when acute infection is identified. New and inexpensive strategies to engage and test individuals at high risk for HIV as well as immediate treatment access will be needed to improve the treatment of acute infection globally. Clinical Trial Number : NCT00796146 and NCT00796263 Keywords HIV; viral load; acute HIV; ART; early treatment; mathematical modelling (Published: 26 June 2017) Ananworanich J et al. Journal of the International AIDS Society 2017, 20 :21652 http://www.jiasociety.org/index.php/jias/article/view/21652 | http://dx.doi.org/10.7448/IAS.20.1.21652