Phyloanatomic characterization of the distinct T cell and monocyte contributions to the peripheral blood HIV population within the host.

Human immunodeficiency virus (HIV) is a rapidly evolving virus, allowing its genetic sequence to act as a fingerprint for epidemiological processes among, as well as within, individual infected hosts. Though primarily infecting the CD4+ T-cell population, HIV can also be found in monocytes, an immune cell population that differs in several aspects from the canonical T-cell viral target. Using single genome viral sequencing and statistical phylogenetic inference, we investigated the viral RNA diversity and relative contribution of each of these immune cell types to the viral population within the peripheral blood.

Brief Report: Group Sex and Methamphetamine Use Fuel an Explosive Epidemic of Hepatitis C Among HIV-Infected Men Who Have Sex With Men in Bangkok, Thailand.

Background: Increased rates of hepatitis C virus (HCV) infection among HIV-infected men who have sex with men (MSM) and who deny injecting drugs have been reported in resource-rich settings.

Setting: We measured HCV prevalence and incidence in a predominantly MSM cohort with acute HIV infection in Bangkok, Thailand.

Methods: In 2009-2018, participants with acute HIV infection were enrolled into the SEARCH010/RV254 cohort.

Implementation of an active case management network to identify HIV-positive infants and accelerate the initiation of antiretroviral therapy, Thailand 2015 to 2018.

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).

Machine-learning classification of neurocognitive performance in children with perinatal HIV initiating de novo antiretroviral therapy.

Objective: To develop a predictive model of neurocognitive trajectories in children with perinatal HIV (pHIV).

Design: Machine learning analysis of baseline and longitudinal predictors derived from clinical measures utilized in pediatric HIV.

Methods: Two hundred and eighty-five children (ages 2-14 years at baseline; Mage = 6.

The rate of bone loss slows after 1-2 years of initial antiretroviral therapy: final results of the Strategic Timing of Antiretroviral Therapy (START) bone mineral density substudy.

Objectives: Initial antiretroviral therapy (ART) causes loss of bone mineral density (BMD) over the first 1-2 years. Whether this loss continues with longer therapy is unclear. We determined changes in bone and spine BMD over 5 years in adults receiving immediate or deferred initial ART.

Behavioral problems in perinatally HIV-infected young children with early antiretroviral therapy and HIV-exposed uninfected young children: prevalence and associated factors.

Although behavioral problems have been observed in children and adolescents with perinatally-acquired HIV infection (PHIV), behavioral information regarding younger PHIV children are scarce. This study aims to identify behavioral problems in PHIV and HIV-exposed uninfected (HEU) children and to evaluate factors associated with such problems. A prospective study of PHIV and HEU young children was conducted.

Infrequent HIV Infection of Circulating Monocytes during Antiretroviral Therapy.

Whereas human immunodeficiency virus (HIV) persists in tissue macrophages during antiretroviral therapy (ART), the role of circulating monocytes as HIV reservoirs remains controversial. Three magnetic bead selection methods and flow cytometry cell sorting were compared for their capacity to yield pure CD14 monocyte populations. Cell sorting by flow cytometry provided the purest population of monocytes (median CD4 T-cell contamination, 0.

Trajectory Analysis of Cognitive Outcomes in Children With Perinatal HIV.

Background: Children with perinatal HIV (pHIV) may display distinct long-term cognitive phenotypes. We used group-based trajectory modeling to identify clusters of children with pHIV after similar developmental trajectories and predictors of belonging to select cognitive trajectory groups.

Methods: Participants included children, 4-17 years of age, with pHIV in Thailand and Cambodia.

Effect of Oral Oseltamivir on Virological Outcomes in Low-risk Adults With Influenza: A Randomized Clinical Trial.

Background: Duration of viral shedding is a determinant of infectivity and transmissibility, but few data exist about oseltamivir's ability to alter viral shedding.

Methods: From January 2012 through October 2017, a randomized, double-blinded multicenter clinical trial was conducted in adults aged 18-64 years at 42 sites in Thailand, the United States, and Argentina. Participants with influenza A or B and without risk factors for complications of influenza were screened for the study.

Low CD4 Cell Counts Are Associated with Carotid Plaque and Intima-Media Thickness in Virologically Suppressed HIV-Infected Asians Older Than 50 Years.

Information about the prevalence, and risk factors for subclinical atherosclerosis in an Asian HIV-infected population is limited. Carotid intima-media thickness (cIMT) is one predictor for the risk of cardiovascular disease (CVDs) and mortality. We evaluated the prevalence and risk factors related to carotid atherosclerosis among well-suppressed HIV-infected adults receiving long-term ART from Thailand.

Emotional and behavioral resilience among children with perinatally acquired HIV in Thailand and Cambodia.

Objectives: Psychosocial challenges associated with perinatally acquired HIV (PHIV) infection are well known, yet many children infected with HIV since birth demonstrate positive outcomes, referred to as resilience. The purpose of this study was to evaluate emotional-behavioral development and identify salient predictors of resilience among long-term survivors of PHIV.

Design: Prospective investigation of children with PHIV compared with demographically similar perinatally HIV-exposed but uninfected (PHEU) and HIV-unexposed, uninfected (HUU) children, all from Thailand and Cambodia.

Third-line antiretroviral therapy in low-income and middle-income countries (ACTG A5288): a prospective strategy study.

Background: Antiretroviral therapy (ART) management is challenging for individuals in resource-limited settings presenting for third-line treatment because of complex resistance patterns, partly due to reduced access to viral load monitoring. We aimed to evaluate use of newer antiretroviral drugs and contemporary management approaches, including population-based sequencing, to select appropriate antiretrovirals, plasma viral load monitoring, and interventions to improve adherence in individuals presenting with second-line viral failure.

Methods: A5288 was a phase 4, third-line ART strategy study done at 19 urban sites in ten countries that enrolled adult participants with confirmed plasma HIV-1 RNA (viral load) of 1000 copies per mL or more after more than 24 weeks of protease inhibitor-based second-line ART.

HIV Incidence and Risk Behaviours of People Who Inject Drugs in Bangkok, 1995-2012.

Background: Three consecutive prospective studies were conducted among people who inject drugs (PWID) from May 1995 through June 2012 in Bangkok, Thailand. We examined data from these studies to evaluate HIV incidence and explore trends in risk behaviours.

Methods: We used data from a 1995-1998 cohort study, a 1999-2004 HIV vaccine trial, and a 2005-2012 HIV pre-exposure prophylaxis (PrEP) study to examine per-quarter trends in HIV incidence, using a restricted cubic spline function for time in a Poisson regression.

Safety and efficacy of VRC01 broadly neutralising antibodies in adults with acutely treated HIV (RV397): a phase 2, randomised, double-blind, placebo-controlled trial.

Background: HIV-1-specific broadly neutralising antibodies such as VRC01 could promote HIV remission by halting viral replication and clearing infected cells. We investigated whether VRC01 could promote sustained viral control off antiretroviral therapy (ART) in adults who initiated ART during acute HIV infection.

Methods: We did a randomised, double-blind, placebo-controlled trial at the Thai Red Cross AIDS Research Centre in Bangkok, Thailand.

Low risk of neurodevelopmental impairment among perinatally acquired HIV-infected preschool children who received early antiretroviral treatment in Thailand.

Introduction: Antiretroviral therapy (ART) is recommended in perinatally HIV-infected (PHIV) infants immediately upon diagnosis. We aimed to compare neurodevelopmental outcomes between PHIV children who initiated ART within 12 months of life and perinatally HIV-exposed uninfected (PHEU) children and to assess neurodevelopmental outcomes by timing of ART.

Methods: This prospective cohort study included Thai children aged 12 to 56 months who were assessed with the Mullen Scales of Early Learning (MSEL) at enrolment and at 48 weeks.

Recommendations for analytical antiretroviral treatment interruptions in HIV research trials-report of a consensus meeting.

Analytical antiretroviral treatment interruption (ATI) is an important feature of HIV research, seeking to achieve sustained viral suppression in the absence of antiretroviral therapy (ART) when the goal is to measure effects of novel therapeutic interventions on time to viral load rebound or altered viral setpoint. Trials with ATIs also intend to determine host, virological, and immunological markers that are predictive of sustained viral control off ART. Although ATI is increasingly incorporated into proof-of-concept trials, no consensus has been reached on strategies to maximise its utility and minimise its risks.

Very Early Initiation of Antiretroviral Therapy During Acute HIV Infection Is Associated With Normalized Levels of Immune Activation Markers in Cerebrospinal Fluid but Not in Plasma.

Background: Chronic immune activation in the blood and central nervous system is a consequence of human immunodeficiency virus (HIV) infection that contributes to disease morbidity and can occur despite virally suppressive antiretroviral therapy (ART). The trajectory of HIV-related inflammation may vary with the timing of ART initiation. We examined immune activation markers in cerebrospinal fluid (CSF) and blood specimens collected over 96 weeks from participants who initiated ART during acute HIV infection (AHI).

Substance use and universal access to HIV testing and treatment in sub-Saharan Africa: implications and research priorities.

As universal testing and treatment for HIV, or 'treat all', expands across sub-Saharan Africa (SSA), substance use will likely have a negative impact on the success of scale-up efforts for antiretroviral treatment (ART). Overwhelming evidence highlights the negative impact of substance use on HIV care and treatment outcomes. Yet, as many countries in SSA expand ART, evidence of the extent of substance use, and its impact in the region, is more limited.

Estimating recent HIV incidence among young men who have sex with men: Reinvigorating, validating and implementing Osmond's algorithm for behavioral imputation.

HIV incidence information is essential for epidemic monitoring and evaluating preventive interventions. However, reliable HIV incidence data is difficult to obtain, especially among marginalized populations, such as young men who have sex with men (YMSM). Here we evaluate the reliability of an alternative HIV incidence assessment method, behavioral imputation, as compared to serologically estimated HIV incidence.

CD4/CD8 ratio normalization rates and low ratio as prognostic marker for non-AIDS defining events among long-term virologically suppressed people living with HIV.

Background: Immune restoration is often incomplete after ART in HIV patients, both quantitatively and qualitatively. We studied the incidence and probability of CD4/CD8 normalization in an adult Thai HIV cohort and explored the predictive value of the ratio for developing of non-AIDS defining events (NAEs).

Methods: We analyzed data from HIV-infected Thai adults between 1996 and 2017 in the HIV-NAT 006 prospective long-term cohort in Bangkok, Thailand.

A flow cytometry based assay that simultaneously measures cytotoxicity and monocyte mediated antibody dependent effector activity.

Antibody effector functions such as antibody dependent cellular cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP) are considered important immunologic parameters following results from the RV144 clinical trial where a reduced risk of infection was associated with non-neutralizing antibody against the V1/V2 region of HIV envelope. The rapid and fluorometric ADCC (RFADCC) assay has been widely used to measure ADCC, however, the mechanism behind the activity measured remains unclear. Here, we demonstrate that monocytes acquire the PKH26 dye used in the RFADCC assay and that the commonly used RFADCC readout correlates with phagocytosis.

"I am not promiscuous enough!": Exploring the low uptake of HIV testing by gay men and other men who have sex with men in Metro Manila, Philippines.

The Philippines faces a severe HIV epidemic among gay and other men who have sex with men (MSM). HIV testing uptake remains low. A case series of 12 men from Metro Manila were interviewed to explore barriers to uptake of HIV testing services.

Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection.

Antiretroviral therapy during the earliest stage of acute HIV infection (Fiebig I) might minimize establishment of a latent HIV reservoir and thereby facilitate viremic control after analytical treatment interruption. We show that 8 participants, who initiated treatment during Fiebig I and were treated for a median of 2.8 years, all experienced rapid viral load rebound following analytical treatment interruption, indicating that additional strategies are required to control or eradicate HIV.

The finding of casual sex partners on the internet, methamphetamine use for sexual pleasure, and incidence of HIV infection among men who have sex with men in Bangkok, Thailand: an observational cohort study.

Background: The finding of casual sex partners on the internet and methamphetamine use have been described as risk factors for HIV infection in men who have sex with men (MSM). However, the interplay between these factors has not been studied prospectively in one design. This study aims to determine the associations between finding casual sex partners on the internet and incident methamphetamine use and HIV infection.

Characterization of Cellular Immune Responses in Thai Individuals With and Without HIV-Associated Neurocognitive Disorders.

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.