Publications by authors named "Donn Colby"

Background: Hepatitis C virus (HCV) coinfection may further compromise immunological and cognitive function in people with HIV (PWH). This study compared laboratory and neuropsychiatric measures across the periods of HCV seroconversion and direct-acting antiviral (DAA) therapy with sustained virologic response (SVR) among PWH who initiated antiretroviral therapy (ART) during acute HIV infection (AHI) and acquired HCV after 24 weeks of ART.

Methods: Participants from the RV254 AHI cohort underwent paired laboratory and neuropsychiatric assessments during follow-up visits.

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Introduction: Data about impact of switch to dolutegravir (DTG)-based antiretroviral therapy (ART) on estimated glomerular filtration rate (eGFR) in Asians are scarce. RV254/SEARCH010 is a prospective observational cohort in Bangkok, Thailand with ART initiation during acute HIV infection (AHI) where participants switched to DTG-based ART.

Methods: Participants started Efavirenz (EFV)-based ART during AHI (n = 214) and switched to DTG-based ART after a median of 97 weeks (IQR 61-145).

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Objectives: We report longitudinal trends in alcohol and recreational drug use, and their associations with sexual behaviors and clinical outcomes in a Thai cohort of predominantly men who have sex with men (MSM) living with HIV.

Methods: From 2017 to 2019, participants in the RV254/SEARCH010 acute HIV cohort answered questions every 24 weeks about drug use and sexual behaviors. Longitudinal trends were assessed using the χ2 test for trend.

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Article Synopsis
  • - The study examined the effects of a heterologous Ad26/MVA vaccine on immune responses in people living with HIV-1 who interrupted their antiretroviral treatment.
  • - It was found that while the vaccine primarily produced binding antibodies related to the vaccine strain, these did not correlate with the time it took for the virus to rebound after treatment interruption.
  • - Individuals who experienced delayed viral rebound had significantly higher levels of antibodies that promote phagocytosis (ADCP), suggesting that vaccines generating cross-reactive immune responses could help in controlling the virus after treatment stops.
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  • MSM living with HIV have a higher risk for anal cancer, particularly due to precursor lesions called high-grade squamous intraepithelial lesions (HSILs), but the incidence among those starting antiretroviral therapy during acute HIV has not been well studied.* -
  • In a study of 89 MSM and 4 transgender women in Bangkok, 11.8% were found to have anal HSIL at the start, with an incidence rate of 19.7 per 100 person-years, influenced by factors like specific HPV types and syphilis.* -
  • The study concluded that while the prevalence of anal HSIL was similar among those initiating treatment during acute HIV and those without HIV, ongoing screening and management
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Background: Hepatitis C virus (HCV) coinfection may further compromise immunological and cognitive function in people with HIV (PWH). This study compared laboratory and neuropsychiatric measures across the periods of HCV seroconversion and direct-acting antiviral (DAA) therapy with sustained virologic response (SVR) among PWH who initiated antiretroviral therapy (ART) during acute HIV infection (AHI) and acquired HCV after 24 weeks of ART.

Methods: Participants from the RV254 AHI cohort underwent paired laboratory and neuropsychiatric assessments during regular follow-up.

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Article Synopsis
  • Sexually transmitted infections (STIs), specifically Mycoplasma genitalium (MG), pose a significant risk to U.S. Armed Forces personnel, potentially affecting their readiness and performance.
  • A study at two military bases analyzed data from 432 participants, finding a 10% prevalence of MG, with higher rates among females and non-Hispanic Black individuals.
  • The research indicates that single relationship status and multiple recent sexual partners are linked to increased MG prevalence, emphasizing the need for further investigation into this emerging pathogen in military settings.
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Objective: HIV-1 invades the brain within days post-transmission. This study quantitated cerebrospinal fluid (CSF) white blood cell count (WBC) and investigated whether it associated with plasma and CSF HIV-1 RNA during untreated acute HIV infection (AHI).

Design: Seventy participants underwent lumbar puncture during Fiebig stages I-V AHI.

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Productively infected cells are generally thought to arise from HIV infection of activated CD4+ T cells, and these infected activated cells are thought to be a recurring source of latently infected cells when a portion of the population transitions to a resting state. We discovered and report here that productively and latently infected cells can instead originate from direct infection of resting CD4+ T cell populations in lymphoid tissues in Fiebig I, the earliest stage of detectable HIV infection. We found that direct infection of resting CD4+ T cells was correlated with the availability of susceptible target cells in lymphoid tissues largely restricted to resting CD4+ T cells in which expression of pTEFb enabled productive infection, and we documented persistence of HIV-producing resting T cells during antiretroviral therapy (ART).

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Background: Although key populations (KPs), such as men-who-have-sex-with-men (MSM) are disproportionately affected by HIV, many prevention and treatment services are not easily accessible for KP members. To address the needs of KPs, Thailand established pre-exposure prophylaxis (PrEP) service delivery together with and led by KP members. This study determines the epidemiological impact and cost-effectiveness of key population-led (KP-led) PrEP.

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Analytic treatment interruption (ATI) is scientifically necessary in HIV-remission ("cure") studies to test the effects of new interventions. However, stopping antiretroviral treatment poses risks to research participants and their sexual partners. Ethical debate about whether and how to conduct such studies has largely centered on designing risk-mitigation strategies and identifying the responsibilities of research stakeholders.

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Objective: People with chronic HIV exhibit lower regional brain volumes compared to people without HIV (PWOH). Whether imaging alterations observed in chronic infection occur in acute HIV infection (AHI) remains unknown.

Design: Cross-sectional study of Thai participants with AHI.

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Objective: We examined individual differences in CD4/CD8 T-cell ratio trajectories and associated risk profiles from acute HIV infection (AHI) through 144 weeks of antiretroviral therapy (ART) using a data-driven approach.

Methods: A total of 483 AHI participants began ART during Fiebig I-V and completed follow-up evaluations for 144 weeks. CD4+, CD8+, and CD4/CD8 T-cell ratio trajectories were defined followed by analyses to identify associated risk variables.

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Background: Harnessing CD8 T cell responses is being explored to achieve HIV remission. Although HIV-specific CD8 T cells become dysfunctional without treatment, antiretroviral therapy (ART) partially restores their function. However, the extent of this recovery under long-term ART is less understood.

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Background: Analytic treatment interruption (ATI) studies evaluate strategies to potentially induce remission in people living with HIV-1 but are often limited in sample size. We combined data from four studies that tested three interventions (vorinostat/hydroxychloroquine/maraviroc before ATI, Ad26/MVA vaccination before ATI, and VRC01 antibody infusion during ATI).

Methods: The statistical validity of combining data from these participants was evaluated.

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Background: Efavirenz (EFV)- and dolutegravir (DTG)-based antiretroviral therapy (ART) is the former and current recommended regimen for treatment-naive individuals with human immunodeficiency virus type 1 (HIV-1). Whether they impact the immunological and neuropsychiatric profile differentially remains unclear.

Methods: This retrospective analysis included 258 participants enrolled during acute HIV-1 infection (AHI).

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Background: Over the past 10 years, incidence of sexually transmitted infections (STIs) has increased to record numbers in the United States, with the most significant increases observed among adolescents and young adults. The US military, where the majority of active duty personnel are 18-30 years old, has seen similar increases. However, the US military does not yet have a standardized, service-wide program for STI education and prevention.

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Starting antiretroviral therapy (ART) in Fiebig 1 acute HIV infection limits the size of viral reservoirs in lymphoid tissues, but does not impact time to virus rebound during a treatment interruption. To better understand why the reduced reservoir size did not increase the time to rebound we measured the frequency and location of HIV RNA+ cells in lymph nodes from participants in the RV254 acute infection cohort. HIV RNA+ cells were detected more frequently and in greater numbers when ART was initiated in Fiebig 1 compared to later Fiebig stages and were localized to the T-cell zone compared to the B-cell follicle with treatment in later Fiebig stages.

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To reach its goal of ending AIDS by 2030, Thailand has adopted antiretroviral treatment as prevention and HIV pre-exposure prophylaxis for men who have sex with men (MSM) and transgender women (TGW) as its core HIV control strategy. However, in the absence of reliable epidemiologic indicators, the impact of these policies on the course of the HIV epidemic in these groups remains unknown. To help answer this question, we formulated an HIV epidemic consensus initiative for Bangkok, Thailand, to analyze epidemiologic and program data and reach agreement between experts and stakeholders on the evolving state of the HIV epidemic among MSM and TGW.

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HIV remission trials often require temporary stopping of antiretroviral therapy (ART)-an approach called analytic treatment interruption (ATI). Trial designs resulting in viremia raise risks for participants and sexual partners. We conducted a survey on attitudes about remission trials, comparing ART resumption criteria (lower-risk "time to rebound" and higher-risk "sustained viremia") among participants from an acute HIV cohort in Thailand.

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HIV-1 disrupts the host epigenetic landscape with consequences for disease pathogenesis, viral persistence, and HIV-associated comorbidities. Here, we examined how soon after infection HIV-associated epigenetic changes may occur in blood and whether early initiation of antiretroviral therapy (ART) impacts epigenetic modifications. We profiled longitudinal genome-wide DNA methylation in monocytes and CD4+ T lymphocytes from 22 participants in the RV254/SEARCH010 acute HIV infection (AHI) cohort that diagnoses infection within weeks after estimated exposure and immediately initiates ART.

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Background: The greater availability of different antiretroviral therapy regimens in developing countries may influence the emergence of transmitted drug resistance (TDR). People with acute HIV infection (AHI) represent the best opportunity for real-time monitoring of TDR. This study assessed the TDR prevalence trends over time in a Thai cohort of predominantly men who have sex with men (MSM) with AHI.

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The health-related quality of life (HRQoL) among persons living with HIV (PLWHA) who initiate ART during acute HIV infection (AHI) is not well studied. Participants in the SEARCH010/RV254 cohort initiated ART during AHI. They completed the Thai version of the World Health Organisation Quality of Life instrument-BREF (WHOQOL-BREF) and Patient Health Questionnaire-9 (PHQ-9) prior to ART initiation and 24 weeks later.

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Article Synopsis
  • Increasing hepatitis C infections among HIV positive men who have sex with men in Bangkok prompted a study on the cost-effectiveness of immediate treatment using direct-acting antivirals (DAAs) to curb transmission.
  • A model analysis revealed that delaying DAA treatment significantly raises HCV incidence rates by 2030, while immediate treatment drops the incidence substantially and is financially advantageous.
  • Immediate DAA treatment not only saves costs but also improves health outcomes by effectively lowering HCV infections among this high-risk population.
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Objective: People with HIV continue to exhibit cognitive symptoms after suppressive antiretroviral therapy (ART). It remains unclear if initiating ART during acute HIV-1 infection (AHI) uniformly improves cognitive outcomes.

Methods: Sixty-seven individuals (96% men, median age 28 years) initiated ART immediately after AHI diagnosis and maintained viral suppression for 6 years.

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