Search

Background Patients living with human immunodeficiency virus (PLWH) with low CD4 counts are at high risk for immune reconstitution inflammatory syndrome (IRIS) and death at antiretroviral therapy (ART) initiation. Methods We investigated the clinical impact of IRIS in PLWH and CD4 counts <100 cells/μL starting ART in an international, prospective study in the United States, Thailand, and Kenya. An independent review committee adjudicated IRIS events. We assessed associations between baseline biomarkers, IRIS, immune recovery at week 48, and death by week 48 with Cox models. Results We enrolled 506 participants (39.3% were women). Median age was 37 years, and CD4 count was 29 cells/μL. Within 6 months of ART, 97 (19.2%) participants developed IRIS and 31 (6.5%) died. Participants with lower hemoglobin at baseline were at higher IRIS risk (hazard ratio [HR], 1.2; P =.004). IRIS was independently associated with increased risk of death after adjustment for known risk factors (HR, 3.2; P =.031). Being female (P =.004) and having a lower body mass index (BMI; P =.003), higher white blood cell count (P =.005), and higher D-dimer levels (P =.044) were also significantly associated with increased risk of death. Decision-tree analysis identified hemoglobin <8.5 g/dL as predictive of IRIS and C-reactive protein (CRP) >106 μg/mL and BMI <15.6 kg/m2 as predictive of death. Conclusions For PLWH with severe immunosuppression initiating ART, baseline low BMI and hemoglobin and high CRP and D-dimer levels may be clinically useful predictors of IRIS and death risk. [ABSTRACT FROM AUTHOR]

Introduction: Antiretroviral treatment (ART) reduces HIV transmission. Despite increased ART coverage, incidence remains high among men who have sex with men (MSM) in many places. Acute HIV infection (AHI) is characterized by high viral replication and increased infectiousness. We estimated the feasible reduction in transmission by targeting MSM with AHI for early ART. Methods: We recruited a cohort of 88 MSM with AHI in Bangkok, Thailand, who initiated ART immediately. A risk calculator based on viral load and reported behaviour, calibrated to Thai epidemiological data, was applied to estimate the number of onwards transmissions. This was compared with the expected number without early interventions. Results: Forty of the MSM were in 4th-generation AHI stages 1 and 2 (4thG stage 1, HIV nucleic acid testing (NAT)+/4thG immunoassay (IA)-/3rdG IA-; 4thG stage 2, NAT+/4thG IA+/3rdG IA-) while 48 tested positive on third-generation IA but had negative or indeterminate western blot (4thG stage 3). Mean plasma HIV RNA was 5.62 log10 copies/ml. Any condomless sex in the four months preceding the study was reported by 83.7%, but decreased to 21.2% by 24 weeks on ART. After ART, 48/88 (54.6%) attained HIV RNA <50 copies/ml by week 8, increasing to 78/87 (89.7%), and 64/66 (97%) at weeks 24 and 48, respectively. The estimated number of onwards transmissions in the first year of infection would have been 27.3 (95% credible interval: 21.7-35.3) with no intervention, 8.3 (6.4-11.2) with post-diagnosis behaviour change only, 5.9 (4.4-7.9) with viral load reduction only and 3.1 (2.4-4.3) with both. The latter was associated with an 88.7% (83.8-91.1%) reduction in transmission. Conclusions: Disproportionate HIV transmission occurs during AHI. Diagnosis of AHI with early ART initiation can substantially reduce onwards transmission. [ABSTRACT FROM AUTHOR]

Background: Data on the performance of interferon-gamma release assays (IGRAs), QuantiFERON TB Gold In-tube (QFNGIT) and T-Spot.TB, in diagnosing tuberculosis (TB) are limited in Southeast Asia. This study aims to compare the performances of the two IGRAs and TST in Thai children with recent TB exposure. Methods: This multicenter, prospective study enrolled children with recent exposure to active TB adults. Children were investigated for active TB. TST was performed and blood collected for T-Spot.TB and QFNGIT. Results: 158 children were enrolled (87% TB-exposed and 13% active TB, mean age 7.2 years). Only 3 children had HIV infection. 66.7% had TST≥10 mm, while 38.6% had TST≥15 mm. 32.5% had positive QFNGIT; 29.9% had positive T-Spot.TB. QFNGIT and T-Spot.TB positivity was higher among children with active TB compared with TB-exposed children. No indeterminate IGRA results were detected. No statistically significant differences between the performances of the IGRAs and TST at the two cut-offs with increasing TB exposure were detected. Concordance for positive IGRAs and TST ranged from 42–46% for TST≥10 mm and 62–67% for TST≥15 mm. On multivariable analyses, exposure to household primary/secondary caregiver with TB was associated with positive QFNGIT. Higher TB contact score and active TB were associated with positive T-Spot.TB. Conclusions: Both QFNGIT and T-Spot.TB performed well in our Thai pediatric study population. No differences in the performances between tests with increasing TB exposure were found. Due to accessibility and low cost, using TST may more ideal than IGRAs in diagnosing latent and active TB in healthy children in Thailand and other similar settings. [ABSTRACT FROM AUTHOR]

Introduction: Liver disease is a common cause of non‐AIDS morbidity and mortality in people living with HIV (PLHIV), but the prevalence and significance of liver function test (LFT) abnormalities in early HIV infection is unknown. This study aimed to characterize LFTs in a large cohort of participants with acute HIV infection initiating immediate antiretroviral therapy (ART) and examine the association between LFTs and biomarkers of HIV infection and inflammation. Methods: We measured LFTs at the time of HIV diagnosis and at 4, 12, 24 and 48 weeks after ART initiation in 426 Thai individuals with acute HIV infection from 2009 to 2018. A subset of individuals had data available at 96 and 144 weeks. We excluded individuals with concomitant viral hepatitis. Alanine aminotransferase (ALT) was the primary outcome of interest; values greater than 1.25 times the upper limit of normal were considered elevated. Analyses utilized descriptive statistics, non‐parametric tests and multivariate logistic regression. Results: Sixty‐six of the 426 individuals (15.5%) had abnormal baseline ALT levels; the majority (43/66, 65.5%) had Grade 1 elevations. Elevated baseline ALT correlated with Fiebig stages III to V (p = 0.001) and baseline HIV RNA >6 log10 copies/mL (p = 0.012). Baseline elevations resolved by 48 weeks on ART in 59 of the 66 individuals (89%). ALT elevations at 24 and 48 weeks correlated with Fiebig stages I to II at diagnosis (p < 0.001), baseline plasma HIV RNA levels <6 log10 copies/mL (p < 0.001), abnormal baseline ALT (p < 0.001), baseline CD4 >350 cells/μL (p = 0.03) and older age (p = 0.03). Individuals initiating efavirenz‐based regimens were more likely to have elevated ALT levels at 48 weeks compared with those on non‐efavirenz‐based regimens (p = 0.003). Conclusions: One in six people with acute HIV infection have elevated LFTs. Clinical outcomes with ART started in acute HIV are generally good, with resolution of ALT elevations within 48 weeks on ART in most cases. These results suggest a multifactorial model for hepatic injury involving a combination of HIV‐associated and ART‐associated processes, which may change over time. [ABSTRACT FROM AUTHOR]

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.

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, 0.06%), and the levels of CD4 + T-cell contamination were positively correlated with the levels of integrated HIV DNA in the monocyte populations. Using cell sorting by flow cytometry, we assessed longitudinally the infection of monocytes and other cell subsets in a cohort of 29 Thai HIV-infected individuals. Low levels of HIV DNA were detected in a minority of monocyte fractions obtained before and after 1 year of ART (27% and 33%, respectively), whereas HIV DNA was readily detected in CD4 + T cells from all samples. Additional samples (2 to 5 years of ART) were obtained from 5 individuals in whom monocyte infection was previously detected. Whereas CD4 + T cells were infected at high levels at all time points, monocyte infection was inconsistent and absent in at least one longitudinal sample from 4/5 individuals. Our results indicate that infection of monocytes is infrequent and highlight the importance of using flow cytometry cell sorting to minimize contamination by CD4 + T cells. IMPORTANCE The role of circulating monocytes as persistent HIV reservoirs during ART is still controversial. Several studies have reported persistent infection of monocytes in virally suppressed individuals; however, others failed to detect HIV in this subset. These discrepancies are likely explained by the diversity of the methods used to isolate monocytes and to detect HIV infection. In this study, we show that only flow cytometry cell sorting yields a highly pure population of monocytes largely devoid of CD4 contaminants. Using this approach in a longitudinal cohort of HIV-infected individuals before and during ART, we demonstrate that HIV is rarely found in monocytes from untreated and treated HIV-infected individuals. This study highlights the importance of using methods that yield highly pure populations of cells as flow cytometry cell sorting to minimize and control for CD4 + T-cell contamination., (Copyright © 2019 American Society for Microbiology.)

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) <18.5 kg/m 2 . Participants were on ART for a median of 124 weeks before switching to DTG. The median (IQR) body weight increased from 63 (56 to 70) kg before to 65 (58 to 73) kg (p < 0.0001) after 48 weeks of DTG. Forty-nine (16%) developed DTG-related AEs, corresponding to an incidence of 16.6 per 100 person-years. Neuropsychiatric symptoms were most frequently encountered (n = 25, 8%), followed by laboratory abnormalities (n = 16, 5%). Six (2%) discontinued DTG, corresponding to an incidence of 2.4 per 100 person-years. All discontinuations were due to increased liver enzymes in the presence of hepatitis C virus coinfection. In the multivariate analysis, incident hepatitis C virus infection was the only risk factor for discontinuing DTG (hazard ratio 59.4, 95% CI 8.5 to 297.9, p < 0.0001). Neither low BMI nor concurrent abacavir therapy was associated with discontinuation., Conclusions: DTG was well tolerated with few discontinuations in this cohort of young men. Incident hepatitis C virus infection was a driver of liver-related AEs leading to discontinuations. In populations at risk, regular testing for hepatitis C virus during ART is recommended to anticipate possible AEs, guide management and improve safety., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: Thailand plays a substantial role in global HIV-1 transmission of CRF01&#95;AE. Worldwide, men who have sex with men (MSM) are at elevated risk for HIV-1 infection. Hence, understanding HIV-1 diversity in a primarily Thai MSM cohort with acute infection, and its connections to the broader HIV-1 transmission network in Asia is crucial for research and development of HIV-1 vaccines, treatment and cure., Methods: Subtypes and diversity of infecting viruses from individuals sampled from 2009 to 2015 within the RV254/SEARCH 010 cohort were assessed by multiregion hybridization assay (MHAbce), multiregion subtype-specific PCR assay (MSSPbce) and full-length single-genome sequencing (SGS). Phylogenetic analysis was performed by maximum likelihood. Pairwise genetic distances of envelope gp160 sequences obtained from the cohort and from Asia (Los Alamos National Laboratory HIV Database) were calculated to identify potential transmission networks., Results: MHAbce/MSSPbce results identified 81.6% CRF01&#95;AE infecting strains in RV254. CRF01&#95;AE/B recombinants and subtype B were found at 7.3% and 2.8% respectively. Western subtype B strains outnumbered Thai B' strains. Phylogenetic analysis revealed one C, one CRF01&#95;AE/CRF02&#95;AG recombinant and one CRF01&#95;AE/B/C recombinant. Asian network analysis identified one hundred and twenty-three clusters, including five clusters of RV254 participants. None of the RV254 sequences clustered with non-RV254 sequences. The largest international cluster involved 15 CRF01&#95;AE strains from China and Vietnam. The remaining clusters were mostly intracountry connections, of which 31.7% included Thai nodes and 43.1% included Chinese nodes., Conclusion: While the majority of strains in Thailand are CRF01&#95;AE and subtype B, emergence of unique recombinant forms (URFs) are found in a moderate fraction of new HIV-1 infections. Approaches to vaccine design and immunotherapeutics will need to monitor and consider the expanding proportion of recombinants and the increasing genetic diversity in the region. Identified HIV-1 transmission networks indicate ongoing spread of HIV-1 among MSM. As HIV-1 epidemics continue to expand in other Asian countries, transmission network analyses can inform strategies for prevention, intervention, treatment and cure., (© 2018 Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Many individuals with acute human immunodeficiency virus infection (AHI) experience acute retroviral syndrome (ARS), which is associated with adverse long-term clinical outcomes., Methods: Participants presenting for voluntary human immunodeficiency virus (HIV) testing were enrolled during AHI in Bangkok, Thailand. ARS was defined by ≥3 qualifying signs/symptoms. HIV burden, immunophenotypes, and biomarkers were stratified by ARS diagnosis at enrollment and after up to 96 weeks of antiretroviral therapy (ART)., Results: From 212382 samples screened, 430 participants were enrolled during AHI, including 335 (78%) with ARS. Median age was 26 years and 416 (97%) were men. Sixty (14%) underwent sigmoid biopsy and 105 (24%) underwent lumbar puncture during AHI. Common symptoms included fever (93%), fatigue (79%), pharyngitis (67%), and headache (64%). Compared to those without ARS, participants with ARS were in later Fiebig stages with higher HIV RNA in blood, colon, and cerebrospinal fluid; higher total HIV DNA in blood; CD4 depletion in blood and colon; and elevated plasma tumor necrosis factor alpha (TNF-α), C-reactive protein, and D-dimer (all P < .05). Subgroup analyses of Fiebig I/II participants (95 with ARS, 69 without) demonstrated similar findings. After 96 weeks of ART, TNF-α and interleukin 6 were elevated in the ARS group (P < .05) but other biomarkers equilibrated., Conclusions: ARS was associated with high viral burden, CD4 depletion, and immune activation across multiple body compartments during AHI and prior to ART. Persistent inflammation despite suppressive ART could contribute to increased morbidity in individuals who experience ARS.

Distal leg epidermal nerve fiber density (ENFD) is a validated predictor of HIV sensory neuropathy (SN) risk. We assessed how ENFD is impacted by initiation of first-time antiretroviral therapy (ART) in subjects free of neuropathy and how it is altered when mitochondrial toxic nucleoside medications are used as part of ART. Serial changes in proximal thigh and distal leg ENFD were examined over 72 weeks in 150 Thai subjects randomized to a regimen of stavudine (d4T) switching to zidovudine (ZDV) at 24 weeks vs ZDV vs tenofovir (TDF) for the entire duration of study, all given in combination with nevirapine. We found individual variations in ENFD change, with almost equal number of subjects who decreased or increased their distal leg ENFD over 72 weeks and no relationship to nucleoside backbone or to development of neuropathic signs or symptoms. Lower baseline distal leg ENFD and greater increases in mitochondrial oxidative phosphorylation complex I (CI) activity were associated with larger increases in distal leg ENFD over 72 weeks. Distal leg ENFD correlated with body composition parameters (body surface area, body mass index, height) as well as with blood pressure measurements. Assessed together with a companion cross-sectional study, we found that mean distal leg ENFD in all HIV+ subjects was lower than in HIV- subjects but similar among HIV+ groups whether ART-naïve or on d4T with/without neuropathy/neuropathic symptoms. The utility of ENFD as a useful predictor of small unmyelinated nerve fiber damage and neuropathy risk in HIV may be limited in certain populations.

Objective: To assess the addition of HIV nucleic acid testing (NAT) to fourth-generation (4thG) HIV antigen/antibody combination immunoassay in improving detection of acute HIV infection (AHI)., Methods: Participants attending a major voluntary counseling and testing site in Thailand were screened for AHI using 4thG HIV antigen/antibody immunoassay and sequential less sensitive HIV antibody immunoassay. Samples nonreactive by 4thG antigen/antibody immunoassay were further screened using pooled NAT to identify additional AHI. HIV infection status was verified following enrollment into an AHI study with follow-up visits and additional diagnostic tests., Results: Among 74 334 clients screened for HIV infection, HIV prevalence was 10.9% and the overall incidence of AHI (N = 112) was 2.2 per 100 person-years. The inclusion of pooled NAT in the testing algorithm increased the number of acutely infected patients detected, from 81 to 112 (38%), relative to 4thG HIV antigen/antibody immunoassay. Follow-up testing within 5 days of screening marginally improved the 4thG immunoassay detection rate (26%). The median CD4 T-cell count at the enrollment visit was 353 cells/μl and HIV plasma viral load was 598 289 copies/ml., Conclusion: The incorporation of pooled NAT into the HIV testing algorithm in high-risk populations may be beneficial in the long term. The addition of pooled NAT testing resulted in an increase in screening costs of 22% to identify AHI: from $8.33 per screened patient to $10.16. Risk factors of the testing population should be considered prior to NAT implementation given the additional testing complexity and costs.

: As use of antiretroviral therapy in Thailand increases, so does the potential for transmission of drug-resistant HIV. We describe the prevalence of WHO surveillance drug resistance mutations among 120 subjects who underwent genotypic testing during acute HIV infection in Bangkok, Thailand. In this cohort of predominantly men who have sex with men, we observed an overall transmitted drug resistance prevalence of 9.2%, including nucleoside/nucleotide analog reverse transcriptase inhibitor 5.0%, nonnucleoside analog reverse transcriptase inhibitor 3.4%, and protease inhibitor 3.4%. These prevalence estimates are higher than previous reports of transmitted drug resistance in Thailand. Baseline drug resistance testing may be warranted, particularly among men who have sex with men.

Objective: A longitudinal cohort study was conducted in Bangkok, Thailand between 2008 and 2013 in order to determine the practice effect of serial neuropsychological testing and establish normative data among normal (HIV-uninfected) Thai volunteers., Material and Method: The authors enrolled 511 cognitively healthy individuals (HIV-uninfected, no drug abuse or other previous/current neurological or psychological conditions) to assess baseline performance on a HIV-specific neuropsychological testing battery. Ninety-nine subjects were re-assessed at 6 and 12 months to evaluate practice effects., Results: The mean age of the 99 subjects completing longitudinal visits was 49.2 years and 53 were male. The authors identified improved mean raw scores on most neuropsychological tests with repeated measurements; however only change in WHO Auditory Verbal Learning Test (AVLT) scores (learning, attention, immediate and delayed recall tasks) met statistical significance, with larger differences seen between baseline and 6-month compared to 6 and 12 months follow-up. Older age correlated with poorer baseline raw score, and was a predictor of worse performance at 6 months and 12 months on several tasks. Level of education was associated with practice effects on several tests. No similar effects were observed with gender., Conclusion: The authors identified improved performance after repeated measurements revealing a significant practice effect on an HIV-specific neuropsychological testing battery employed in Bangkok, Thailand. Main predictors were age and educational attainment.

Background: HIV-positive men who have sex with men (MSM) have a higher prevalence of anal human papillomavirus (HPV) infection and anal cancer incidence than HIV-negative MSM. High-risk HPV persistence is an important risk factor for the development of anal cancer., Methods: A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled from the Thai Red Cross AIDS Research Centre in Bangkok, Thailand, and followed for 12 months. Anal sample collection for HPV genotyping was performed at every visit. HPV prevalence, incidence, clearance, and persistence were calculated. A logistic regression model was used to study factors associated with high-risk HPV persistence., Results: The prevalence of any anal HPV infection was 85% in HIV-positive and 58.5% in HIV-negative MSM (P < 0.0001). The prevalence of high-risk HPV infection was 57.5% in HIV-positive and 36.6% in HIV-negative MSM (P = 0.001). HPV 16 was the most common high-risk HPV type. HIV-positive MSM had a higher prevalence (22.5% vs. 9.8%, P = 0.008) and persistence (16.7% vs. 1.3%, P < 0.001) of HPV 16 than HIV-negative MSM and a trend for higher incidence (16.1 vs. 6.1 episodes/1000 person-months, incidence rate ratio 2.6, P = 0.058). HIV infection (odds ratio: 4.45, 95% confidence interval: 2.11 to 9.4, P < 0.001) and smoking in HIV-positive MSM (odds ratio: 2.3, 95% confidence interval: 1.17 to 4.5, P = 0.015) were independently associated with high-risk HPV persistence in multivariate models., Conclusions: In addition to targeting HIV-positive MSM who are at higher risk for anal, high-risk HPV persistence, anal cancer prevention programs should also integrate behavioral interventions such as smoking cessation to modify risk for high-risk HPV persistence.