Prevalence of Urogenital Mycoplasma genitalium Infection at 2 US Army Medical Facilities.

BACKGROUND: Sexually transmitted infections (STIs) have a high incidence in the US Armed Forces and can adversely impact service members' ability to perform their duties. Better knowledge of Mycoplasma genitalium (MG) epidemiology in the military is needed to understand the potential impact of this emerging pathogen on force readiness. METHODS: We conducted cross-sectional analyses of data from US Army service members and other Military Health System beneficiaries participating in a trial of an STI/HIV behavioral intervention at Fort Liberty, NC, and Joint Base Lewis-McChord, WA. At enrollment, participants completed questionnaires and provided biological specimens for nucleic acid amplification testing for MG, Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG). We used principal component analysis and robust Poisson regression to examine associations between participant characteristics and prevalent urogenital MG. RESULTS: Among 432 participants enrolled between November 2020 and February 2023, 43 had MG (prevalence, 10.0%), of whom 13 had coinfection with another bacterial STI (all 13 were positive for CT, with 1 also positive for NG). The prevalence of MG was significantly higher among female (13.5%) versus male (7.6%; P = 0.048) participants and non-Hispanic Black (14.9%) versus non-Hispanic White participants (6.6%; P = 0.045). Single relationship status and increased number of recent sexual partners were correlated, and their component was associated with higher MG prevalence (adjusted prevalence ratio, 2.11; 95% confidence interval, 1.29-3.48). CONCLUSIONS: The high prevalence of urogenital MG among Military Health System beneficiaries highlights the importance of understanding the potential clinical sequelae of MG and conducting additional epidemiologic research in military settings.

Initial productive and latent HIV infections originate in vivo by infection of resting T cells.

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). Thus, we provide evidence of a mechanism by which direct infection of resting T cells in lymphoid tissues to generate productively and latently infected cells creates a mechanism by which the productively infected cells can replenish both populations and maintain two sources of virus from which HIV infection can rebound, even if ART is instituted at the earliest stage of detectable infection.

Brain volumetrics differ by Fiebig stage in acute HIV infection.

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. METHODS: One hundred and twelve Thai males with AHI (age 20-46) and 18 male Thai PWOH (age 18-40) were included. Individuals with AHI were stratified into early (Fiebig I-II; n  = 32) and late (Fiebig III-V; n  = 80) stages of acute infection using validated assays. T1-weighted scans were acquired using a 3 T MRI performed within five days of antiretroviral therapy (ART) initiation. Volumes for the amygdala, caudate nucleus, hippocampus, nucleus accumbens, pallidum, putamen, and thalamus were compared across groups. RESULTS: Participants in late Fiebig stages exhibited larger volumes in the nucleus accumbens (8% larger; P  = 0.049) and putamen (19%; P  < 0.001) when compared to participants in the early Fiebig. Compared to PWOH, participants in late Fiebig exhibited larger volumes of the amygdala (9% larger; P  = 0.002), caudate nucleus (11%; P  = 0.005), nucleus accumbens (15%; P  = 0.004), pallidum (19%; P  = 0.001), and putamen (31%; P  < 0.001). Brain volumes in the nucleus accumbens, pallidum, and putamen correlated modestly with stimulant use over the past four months among late Fiebig individuals ( P s < 0.05). CONCLUSIONS: Findings indicate that brain volume alterations occur in acute infection, with the most prominent differences evident in the later stages of AHI. Additional studies are needed to evaluate mechanisms for possible brain disruption following ART, including viral factors and markers of neuroinflammation.

Long-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8+ T cells.

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. METHODS: We analyzed the differentiation status and function of HIV-specific CD8+ T cells after long-term ART initiated in acute or chronic HIV infection ex vivo and upon in vitro recall. FINDINGS: ART initiation in any stage of acute HIV infection promoted the persistence of long-lived HIV-specific CD8+ T cells with high expansion (P<0·0008) and cytotoxic capacity (P=0·02) after in vitro recall, albeit at low cell number (P=0·003). This superior expansion capacity correlated with stemness (r=0·90, P=0·006), measured by TCF-1 expression, similar to functional HIV-specific CD8+ T cells found in spontaneous controllers. Importanly, TCF-1 expression in these cells was associated with longer time to viral rebound ranging from 13 to 48 days after ART interruption (r =0·71, P=0·03). In contrast, ART initiation in chronic HIV infection led to more differentiated HIV-specific CD8+ T cells lacking stemness properties and exhibiting residual dysfunction upon recall, with reduced proliferation and cytolytic activity. INTERPRETATION: ART initiation in acute HIV infection preserves functional HIV-specific CD8+ T cells, albeit at numbers too low to control viral rebound post-ART. HIV remission strategies may need to boost HIV-specific CD8+ T cell numbers and induce stem cell-like properties to reverse the residual dysfunction persisting on ART in people treated after acute infection prior to ART release. FUNDING: U.S. National Institutes of Health and U.S. Department of Defense.

Individual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection.

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. RESULTS: Participants had a median viral load (VL) of 5.88 copies/ml and CD4/CD8 T-cell ratio of 0.71 at enrollment. After 144 weeks of ART, the median CD4/CD8 T-cell ratio was 1.3. Longitudinal models revealed five CD4/CD8 T-cell ratio subgroups: group 1 (3%) exhibited a ratio >1.0 at all visits; groups 2 (18%) and 3 (29%) exhibited inversion at enrollment, with normalization 4 and 12 weeks after ART, respectively; and groups 4 (31%) and 5 (18%) experienced CD4/CD8 T-cell ratio inversion due to slow CD4+ T-cell recovery (group 4) or high CD8+ T-cell count (group 5). Persistent inversion corresponded to ART onset after Fiebig II, higher VL, soluble CD27 and TIM-3, and lower eosinophil count. Individuals with slow CD4+ T-cell recovery exhibited higher VL, lower white blood cell count, lower basophil percent, and treatment with standard ART, as well as worse mental health and cognition, compared with individuals with high CD8+ T-cell count. CONCLUSIONS: Early HIV disease dynamics predict unfavorable CD4/CD8 T-cell ratio outcomes after ART. CD4+ and CD8+ T-cell trajectories contribute to inversion risk and correspond to specific viral, immune, and psychological profiles during AHI. Adjunctive strategies to achieve immune normalization merit consideration.

Acute HIV-1 infection viremia associate with rebound upon treatment interruption.

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. Eleven variables, including HIV-1 viral load at diagnosis, Fiebig stage, and CD4+ T cell count were evaluated using pairwise correlations, statistical tests, and Cox survival models. FINDINGS: Participants had homogeneous demographic and clinical characteristics. Because an antiviral effect was seen in participants who received VRC01 infusion post-ATI, these participants were excluded from the analysis, permitting a pooled analysis of 53 participants. Time to viral rebound was significantly associated with variables measured at the beginning of infection: pre-antiretroviral therapy (ART) viral load (HR = 1.34, p = 0.022), time to viral suppression post-ART initiation (HR = 1.07, p < 0.001), and area under the viral load curve (HR = 1.34, p = 0.026). CONCLUSIONS: We show that higher viral loads in acute HIV-1 infection were associated with faster viral rebound, demonstrating that the initial stage of HIV-1 infection before ART initiation has a strong impact on viral rebound post-ATI years later. FUNDING: This work was supported by a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the US Department of the Army (W81XWH-18-2-0040). This research was funded, in part, by the US National Institute of Allergy and Infectious Diseases (AAI20052001) and the I4C Martin Delaney Collaboratory (5UM1AI126603-05).

Feasibility, acceptability, and short-term impact of a brief sexually transmitted infection intervention targeting U.S. Military personnel and family members.

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. METHODS: The KISS intervention (Knocking out Infections through Safer-sex and Screening) was adapted from an evidence-based intervention endorsed by the US Centers for Disease Control and Prevention and consisted of a one-time, small group session. Content included STI/HIV knowledge and prevention, condom use skills, and interpersonal communication techniques. The intervention was pilot tested for feasibility and acceptability among a population of service members and medical beneficiaries at Joint Base Lewis-McChord in Washington state. RESULTS: A total of 79 participants aged 18-30 years were consented to participate in the pilot study and met entry criteria, 66/79 (82.5%) attended the intervention session, and 46/66 (69.7%) returned at 3 months for the final follow-up assessment. The intervention sessions included 31 male (47.0%) and 35 female (53.0%) participants. Almost all participants felt comfortable discussing sexual issues in the group sessions, reported that they intended to practice safer sex after the intervention, and would also recommend the intervention to friends. Knowledge about STI/HIV prevention significantly increased after the intervention, and intervention effects were maintained at 3 months. About one-fifth of participants tested positive for N. gonorrhea or C. trachomatis infection at enrollment, while none had recurrent STIs at the final visit. Use of both male and female condoms increased after the intervention. CONCLUSIONS: The KISS intervention was feasible to implement in the military setting and was acceptable to the active duty service members and other medical beneficiaries who participated in the pilot project. Further studies are needed to determine if the KISS intervention, or others, effectively decrease STI incidence in active duty personnel and would be appropriate for more widespread implementation. TRIAL REGISTRATION: Retrospectively registered as the pilot phase of clinicaltrials.gov NCT04547413 , "Prospective Cohort Trial to Assess Acceptability and Efficacy of an Adapted STI/HIV Intervention Behavioral Intervention Program in a Population of US Army Personnel and Their Medical Beneficiaries-Execution Phase."

Paradoxically Greater Persistence of HIV RNA-Positive Cells in Lymphoid Tissue When ART Is Initiated in the Earliest Stage of Infection.

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. Variability of virus production in people treated during acute infection suggests that the balance between virus-producing cells and the immune response to clear infected cells rapidly evolves during the earliest stages of infection. Clinical Trials Registration: NCT02919306.

HIV prevalence and incidence among men who have sex with men and transgender women in Bangkok, 2014-2018: Outcomes of a consensus development initiative.

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. A customized Delphi process was used to consult and consolidate viewpoints of experts and stakeholders. Experts presented and discussed HIV prevalence and incidence data from recent and ongoing studies among MSM and TGW in Bangkok (2014 to 2018) during a meeting with stakeholders representing government, donors, and civil society. Agreement about the course of the HIV epidemic among MSM and TGW was attained by voting consensus. Based on presented data, meeting participants agreed that HIV prevalence and incidence had decreased among Bangkok MSM from 2014 to 2018. Despite these declines, HIV prevalence and incidence were found to remain high. This was particularly the case among younger MSM. Participants agreed that there was no evidence for a decrease in HIV prevalence and incidence among Bangkok TGW. Introduction of antiretroviral treatment as prevention and HIV pre-exposure prophylaxis may have contributed to these declines. However, HIV prevalence and incidence remained high, and no signs of a decrease were reported among Bangkok TGW. At the current rate of new HIV infections in MSM and TGW, Thailand will not reach its goal of ending AIDS by 2030. This HIV consensus initiative may serve as a model for building agreement and advocacy on epidemiologic and program data and their implications for a large metropolitan city.

Attitudes About Analytic Treatment Interruption (ATI) in HIV Remission Trials with Different Antiretroviral Therapy (ART) Resumption Criteria.

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. Analyses included Wilcoxon-Ranks and multivariate logistic analysis. Most of 408 respondents supported ATI trials, with slightly higher approval of, and willingness to participate in, trials using time to rebound versus sustained viremia criteria. Less than half of respondents anticipated disclosing trial participation to partners and over half indicated uncertainty or unwillingness about whether partners would be willing to use PrEP. Willingness to participate was higher among those who rated higher trial approval, lower anticipated burden, and those expecting to make the decision independently. Our findings support acceptability of ATI trials among most respondents. Participant attitudes and anticipated behaviors, especially related to transmission risk, have implications for future trial design and informed consent.

The epidemiological impact and cost-effectiveness of key population-led PrEP delivery to prevent HIV among men who have sex with men in Thailand: A modelling study.

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. Methods: We calibrated a compartmental deterministic HIV transmission model to the HIV epidemic among Thai MSM. Besides KP-led PrEP, we included other Thai service delivery models of PrEP (fee-based PrEP, the government PrEP program).Data on consistent PrEP use (5 years daily use, 95% effectiveness for preventing HIV) came from Thai PrEP delivery models. For the period 2015-2032, we ranged the number of PrEP starters (40,000-120,000), effectiveness of PrEP (45%-95%), and proportion of consistent users (10%-50%). The analysis started in 2015 when PrEP was introduced. A cost-effectiveness ratio of <160,000 Baht per quality-adjusted life year (QALY) over 40 years was cost-effective. Findings: Without PrEP, 53,800 (interquartile range 48,700-59,700) new HIV infections are expected in 2015-2032. KP-led PrEP was found to have the strongest epidemiological impact of all delivery models averting 58% of infections compared to without PrEP. The epidemiological impact depends on the number of PrEP starters and proportion of consistent use. Although all PrEP service delivery models are cost-effective, KP-led PrEP is most cost-effective with incremental cost-effectiveness ratios of 28,000-37,300 Thai Baht per QALY. Interpretation: Our model projects KP-led PrEP having the greatest epidemiological impact and being the most cost-effective service delivery model of PrEP in Thailand. Funding: This study was supported by the US Agency for International Development and U.S. President's Emergency Plan for AIDS Relief through the Linkages Across the Continuum of HIV Services for Key Populations cooperative agreement (AID-OAA-A-14- 0045) managed by FHI 360.

Persons living with HIV treated in acute HIV infection report good health-related quality of life in Thailand.

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. Of 452 participants, 406 (90%) completed the WHOQOL-BREF. The median age was 26 years (IQR 22-31), and 98% were men. All WHOQOL-BREF domains demonstrated good internal consistency (Cronbach's alpha >0.70). Confirmatory factor analysis validated the WHOQOL-BREF model. 90% of Pearson correlations between domain scores and general facet items were >0.50. HRQoL in all domains was worse among those with at least moderately severe depression (PHQ-9 ≥ 10) (p<0.0001), supporting discriminant validity. At 24 weeks, there was an improvement of scores in all domains (physical, psychological, social, and environmental) and general facet items (p<0.0001), and the range of mean domain scores was 14.7-15.6 (SD 2.3-2.8). The majority of participants (58-63%) had improved HRQoL in the physical, psychological and environmental domains. It is concluded that HRQoL improves 6 months after initiation of ART in AHI, suggesting a benefit of early ART initiation.

Brief Report: Prevalence Trend of Transmitted Drug Resistance in a Prospective Cohort of Thai People With Acute HIV Infection.

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. METHODS: At the time of RV254/SEARCH010 study (NCT00796146) enrollment and before starting ART, HIV genotyping was used to identify mutations in the reverse transcriptase and protease genes. Testing for TDR mutations was obtained by a validated in-house method with TRUGENE assay in a subset. Genotype sequences were analyzed using the Stanford University HIV Drug Resistance Database. RESULTS: Genotyping was performed for 573 participants with AHI. Their median age was 26 years (interquartile range 22-31), 97.4% were men, and 94.1% were MSM. Overall TDR prevalence was 7.0%, declining from 12.5% in 2009-2010 to 4.8% in 2017-2018. A declining resistance prevalence to nonnucleoside reverse transcriptase inhibitor emerged from 9.4% in 2009-2010 to 3.5% in 2017-2018 and to nucleoside reverse transcriptase inhibitor from 6.3% to 2.1%. Protease inhibitor resistance showed a decreased TDR level from 3.1% in 2009-2010 to 1.4% in 2017-2018. CONCLUSIONS: We report an encouraging declining trend in TDR prevalence in a Thai cohort of mainly MSM from 2009 to 2018; in 2017-2018, we observed a low TDR prevalence according to the World Health Organization definition.

Brief Report: Syphilis Incidence and Effect on Viral Load, CD4, and CD4/CD8 Ratio in a Thai Cohort of Predominantly Men Who Have Sex With Men Living With HIV.

BACKGROUND: Syphilis has been increasing in the past years, especially among men who have sex with men (MSM). The aim of the study was to assess syphilis prevalence and incidence and changes in CD4 count and viremia in the RV254 cohort of persons living with HIV who initiated antiretroviral therapy during acute HIV infection (AHI) in Bangkok, Thailand. METHODS: From 2009 to 2018, all cohort participants with AHI were tested for syphilis using a qualitative treponemal chemiluminescent microparticle immunoassay and rapid plasma reagin on enrollment, every 24-48 weeks thereafter and when clinically indicated. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with incident syphilis. RESULTS: Among 579 participants, the median age was 26 (interquartile range: 22-31) years and 564 (97.4%) were men. Syphilis prevalence at enrollment was 14.3% and incidence was 10.2 cases per 100 person-years. Participants with syphilis were more likely to be MSM (HR 3.68, 95% CI: 1.16 to 11.62), use methamphetamine (HR 2.31, 95% CI: 1.51 to 3.54), and have hepatitis C (HR 2.63, 95% CI: 1.59 to 4.34). HIV RNA >50 copies/mL occurred in 6 (3.9%) participants at incident syphilis diagnosis and in 6 (3.9%) after syphilis treatment. Median CD4 count (cells/mm3) declined from 663 before syphilis to 624 at syphilis diagnosis (P = 0.07), rising again to 660 after syphilis treatment. CONCLUSION: Syphilis was common in the RV254 cohort, inducing a marginal but significant impact on HIV RNA and a temporary decline in CD4. Syphilis screening and behavioral risk reduction counseling should be implemented for MSM with AHI in Thailand.

Central Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials: An Observational Study in Acutely Treated People Living With Human Immunodeficiency Virus.

BACKGROUND: The central nervous system (CNS) is a likely reservoir of human immunodeficiency virus (HIV), vulnerable to viral rebound, inflammation, and clinical changes upon stopping antiretroviral therapy (ART). It is critical to evaluate the CNS safety of studies using analytic treatment interruption (ATI) to assess HIV remission. METHODS: Thirty participants who started ART during acute HIV infection underwent CNS assessments across 4 ATI remission trials. ART resumption occurred with plasma viral load >1000 copies/mL. CNS measures included paired pre- vs post-ATI measures of mood, cognitive performance, and neurologic examination, with elective cerebrospinal fluid (CSF) sampling, brain diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). RESULTS: Median participant age was 30 years old and 29/30 were male. Participants' median time on ART before ATI was 3 years, and ATI lasted a median of 35 days. Post-ATI, there were no differences in median mood scores or neurologic findings and cognitive performance improved modestly. During ATI, a low level of CSF HIV-1 RNA was detectable in 6 of 20 participants with plasma viremia, with no group changes in CSF immune activation markers or brain DTI measures. Mild worsening was identified in post-ATI basal ganglia total choline MRS, suggesting an alteration in neuronal membranes. CONCLUSION: No adverse CNS effects were observed with brief, closely monitored ATI in participants with acutely treated HIV, except an MRS alteration in basal ganglia choline. Further studies are needed to assess CNS ATI safety in HIV remission trials, particularly for studies using higher thresholds to restart ART and longer ATI durations.

A randomized trial of vorinostat with treatment interruption after initiating antiretroviral therapy during acute HIV-1 infection.

OBJECTIVE AND DESIGN: A randomized, open-label pilot study in individuals treated with antiretroviral therapy (ART) since acute HIV infection (AHI) with a regimen including a histone deacetylase inhibitor to induce HIV from latency and control HIV replication during subsequent treatment interruption (TI). METHODS: Fifteen participants who initiated ART at AHI were randomized to vorinostat/hydroxychloroquine/maraviroc (VHM) plus ART (n â€‹= â€‹10) or ART alone (n â€‹= â€‹5). The VHM arm received three 14-day vorinostat cycles within 10 weeks before TI. ART was resumed for plasma viral load (VL) â€‹> â€‹1,000 HIV RNA copies/mL. Primary outcome was proportion of participants on VHM â€‹+ â€‹ART versus ART only with VL â€‹< â€‹50 copies/mL for 24 weeks after TI. RESULTS: Fifteen participants on ART (median: 178 weeks: range 79-295) enrolled. Two on VHM â€‹+ â€‹ART experienced serious adverse events. Fourteen participants underwent TI; all experienced VL rebound with no difference in time between arms: VHM â€‹+ â€‹ART (n â€‹= â€‹9) median: 4 weeks and ART only (n â€‹= â€‹5) median: 5 weeks. VHM induced a 2.2-fold increase in VL (p â€‹= â€‹0.008) by single-copy HIV RNA assay after the first cycle. Neopterin levels increased significantly following the first two cycles. After VHM treatment, the frequencies of peripheral blood mononuclear cells harboring total HIV DNA and cell-associated RNA were unchanged. All participants achieved VL suppression following ART re-initiation. CONCLUSIONS: Administration of VHM increased HIV VL in plasma, but this was not sustained. VHM did not impact time to viral rebound following TI and had no impact on the size of the HIV reservoir, suggesting that HIV reservoir elimination will require alternative treatment strategies.

Inflammatory Biomarkers Do Not Differ Between Persistently Seronegative vs Seropositive People With HIV After Treatment in Early Acute HIV Infection.

Persistent viral activity may cause enduring seropositivity and inflammation in treated people with HIV (PWH). We compared inflammatory biomarkers between early treated PWH who remained seronegative or seroconverted and found similar levels of D-dimer, soluble cluster of differentiation 14, C-reactive protein, and interleukin-6, indicating that seronegativity does not affect chronic inflammation in early treated PWH.

Determinants of suboptimal CD4+ T cell recovery after antiretroviral therapy initiation in a prospective cohort of acute HIV-1 infection.

INTRODUCTION: Up to 30% of individuals treated with antiretroviral therapy (ART) during chronic HIV fail to recover CD4 counts to >500 cells/mm3 despite plasma viral suppression. We investigated the frequency and associations of suboptimal CD4 recovery after ART started during acute HIV infection (AHI). METHODS: Participants who started ART in Fiebig I to V AHI with ≥48 weeks of continuous documented HIV-RNA < 50 copies/mL were stratified by CD4 count at latest study visit to suboptimal immune recovery (SIR; CD4 < 350 cells/mm3 ), intermediate immune recovery (IIR; 350 ≤ CD4 < 500) and complete immune recovery (CIR; CD4 ≥ 500). Clinical and laboratory parameters were assessed at pre-ART baseline and latest study visit. Additional inflammatory and neurobehavioral endpoints were examined at baseline and 96 weeks. RESULTS: Of 304 participants (96% male, median 26 years old) evaluated after median 144 (range 60 to 420) weeks of ART initiated at median 19 days (range 1 to 62) post-exposure, 3.6% (n = 11) had SIR and 14.5% (n = 44) had IIR. Pre-ART CD4 count in SIR compared to CIR participants was 265 versus 411 cells/mm3 (p = 0.002). Individuals with SIR or IIR had a slower CD4 rate of recovery compared to those with CIR. Timing of ART initiation by Fiebig stage did not affect CD4 count during treatment. Following ART, the CD8+ T cell count (p = 0.001) and CD4/CD8 ratio (p = 0.047) were lower in SIR compared to CIR participants. Compared to the CIR group at week 96, the combined SIR and IIR groups had higher sCD14 (p = 0.008) and lower IL-6 (p = 0.04) in plasma, without differences in neuropsychological or psychiatric indices. CONCLUSIONS: Despite immediate and sustained treatment in AHI, suboptimal CD4 recovery occurs uncommonly and is associated with low pre-ART CD4 count as well as persistent low CD8 count and CD4/CD8 ratio during treatment.

Large transmission cluster of acute hepatitis C identified among HIV-positive men who have sex with men in Bangkok, Thailand.

A rapidly emerging and highly concentrated hepatitis C virus (HCV) outbreak has recently been observed among both acute and chronic HIV-positive men who have sex with men (MSM) in Bangkok, Thailand. NS5B regions of the HCV genome were amplified using nested PCR and sequenced. Phylogenetic inference was constructed by Maximum Likelihood methods and clusters were identified with support and genetic distance thresholds of 85% and of 4.5%. Forty-eight (25 acute HIV and 23 chronic HIV) MSM with incident HCV infection were included in the analysis. HCV genotype (GT) was 85% GT 1a and 15% GT 3a or 3b. Median age at HCV diagnosis was 34 (interquartile range, 28-41) years. 83.3% (40/48) had history of syphilis infection and 36% (16/44) reported crystal methamphetamine use. Only 2 (4%) reported ever injecting drugs, both crystal methamphetamine. In the phylogenetic clustering analysis, 83% belonged to one of two clusters: one large (75%) and one small (8%) cluster. All clusters were GT 1a. MSM with acute HIV infection were more likely to be in a cluster (92%) than those with chronic infection (74%). HCV screening should be regularly performed for MSM in ART clinics, and offering direct-acting antiviral agents to all MSM with HCV infection might contain the HCV epidemic from expanding further.

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. HCV antibody was measured at enrollment and at least once annually. Infection was confirmed with HCV RNA. Risk factors for HCV were analyzed by proportional hazards regression, with hazard ratios (HRs) calculated in a multivariable model. RESULTS: Of 573 participants, 94% were MSM, with a median age of 26 years (range 18-70 years). The prevalence of HCV antibody was 9 of the 573, or 1.6% [95% confidence interval (CI): 0.7% to 3.0%]. In 1883 person-years (PY) of follow-up, 39 incident cases were identified (20.7 per 1000 PY, 95% CI: 15.1 to 28.3). All incident cases were identified from 2014 onward, and incidence rose from a range of 7.5-11.4 per 1000 PY between 2014 and 2016 to 44.8 per 1000 PY in 2018 (P = 0.001). Most cases (97.4%) were MSM and denied injecting drugs (37 of the 39, 94.5%). In multivariate analysis, methamphetamine use [adjusted HR 2.33 (95% CI: 1.13 to 4.8), P = 0.022], group sex [adjusted HR 2.54 (95% CI: 1.26 to 5.12), P = 0.009], and a history of positive Treponema pallidum hemagglutination or rapid plasma reagin [adjusted HR 2.43 (95% CI: 1.22 to 4.85), P = 0.012] were significantly associated with incident HCV. CONCLUSION: We report an HCV epidemic among this cohort of HIV-infected Bangkok-based MSM. Access to timely HCV diagnosis and treatment is needed to prevent morbidity and to decrease onward transmission.