Acute HIV infection detection and immediate treatment estimated to reduce transmission by 89% among men who have sex with men in Bangkok

Published 28 June 2017Introduction: 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.Eugène D.M.B. Kroon, Nittaya Phanuphak, Andrew J. Shattock, James L.K. Fletcher, Suteeraporn Pinyakorn, Nitiya Chomchey, Siriwat Akapirat, Mark S. de Souza, Merlin L. Robb, Jerome H. Kim, Frits van Griensven, Jintanat Ananworanich, and David P. Wilson on behalf of the RV254/SEARCH 010 Study Grou

Leveraging early HIV diagnosis and treatment in Thailand to conduct HIV cure research

Thailand has the highest prevalence of HIV among countries in Asia but has also been a pioneer in HIV prevention and treatment efforts in the region, reducing the incidence of new infections significantly over the last two decades. Building upon this remarkable history, Thailand has set an ambitious goal to stop the AIDS epidemic in the country by 2030. A key component of the strategy to achieve this goal includes scale-up of HIV screening programs to facilitate early HIV diagnosis and investment in mechanisms to support immediate initiation of antiretroviral therapy (ART). Initiation of ART during early or acute HIV infection not only reduces viremia, thereby halting onward transmission of HIV, but also may facilitate HIV remission by reducing the size of the latent HIV reservoir and preserving immune function. In Thailand, many efforts have been made to reduce the time from HIV infection to diagnosis and from diagnosis to treatment, especially among men who have sex with men and transgender women. Successfully identifying and initiating ART in individuals with acute HIV infection has been leveraged to conduct groundbreaking studies of novel strategies to achieve HIV remission, including studies of broadly-neutralizing HIV-specific monoclonal antibodies and candidate therapeutic vaccines. These efforts have mostly been deployed in Bangkok and future efforts should include other urban and more rural areas. Continued progress in HIV prevention, screening, and treatment will position Thailand to substantially limit new infections and may pave the way for an HIV cure

Neuropsychiatric outcomes before and after switching to dolutegravir-based therapy in an acute HIV cohort

Introduction: Dolutegravir (DTG)-based antiretroviral therapy (ART) is currently the first-line treatment for people living with HIV. Neuropsychiatric adverse events (NP-AEs) have been reported with DTG but neuropsychiatric symptoms have not been systemically quantified using structured scales. This study examined mood and cognitive parameters before and after a planned transition from non-DTG to DTG-based ART within a longitudinal study of acute HIV infection (AHI). Methods: RV254 AHI cohort participants on ≥ 24 weeks of ART initiated at AHI underwent sequential assessments before and after the switch including: (1) Patient Health Questionnaire-9 (PHQ-9), a 9-item survey (scores 0-27) that evaluates somatic and affective/cognitive symptoms of depression; (2) a 2-Questions screening that has been validated locally for depression; (3) Distress Thermometer (scores 0-10); and 4) administration of a 4-test neurocognitive battery sensitive to HIV. Results: 254 individuals (95% male, median age 30) switched to a DTG-based regimen after a median 144 weeks of ART. Serial assessments were completed at a median of 19 weeks before and 37 weeks after DTG. There was a modest but statistically significant increase in PHQ-9 scores after DTG (pre-switch: 5 [IQR 1-7] vs. Post-switch: 5 [IQR 2-8], p = 0.009). The percentage of participants with at least moderate depression (PHQ-9 ≥ 10) increased from 10 to 16% (p = 0.006), but the frequency of moderate-severe depression (PHQ-9 ≥ 15) remained unchanged (3%). No volunteer reported NP-AEs within the study period. Somatic symptoms of depression increased more than cognitive/affective symptoms. Plasma viral suppression (HIV-1 RNA < 50; p = 0.005) and PHQ-9 ≥ 10 (p < 0.001) before switch were linked to lower PHQ-9 scores after DTG in multivariable analysis. Performance on all neuropsychological tests, except grooved pegboard test, improved modestly after DTG (all p < 0.05). Conclusion: After a median duration of 37 weeks of DTG use, there was a modest increase in the higher quartile of PHQ-9. This increase was associated with a rise in moderate depression symptoms but not the more severe forms of depression on PHQ-9. No clinically relevant NP-AEs were reported. Pre-existing depression was not associated with subsequent worsening of symptoms after DTG. Cognitive test performance improved post-DTG but could be due to practice effect

Brief Report: Safety of Frequent Blood Sampling in Research Participants in an Acute HIV Infection Cohort in Thailand

Anemia is a potential adverse effect of phlebotomy during participation in research. Clinical studies of acute HIV infection (AHI) require frequent phlebotomy to maximize scientific yield, but this participant population may also be at increased risk for anemia and other adverse events. The objective of this study was to describe baseline and longitudinal hemoglobin changes among participants with AHI. Participants with AHI (n = 202) were enrolled in a prospective cohort study in Thailand. AHI was diagnosed using pooled nucleic acid testing and sequential HIV antibody immunoassays. Antiretroviral therapy was initiated on enrollment. During 48 weeks of study participation, a total of 629 mL of blood was drawn over 14 visits. Hemoglobin levels were measured serially, and abnormalities were graded using the Division of AIDS (National Institute of Allergy and Infectious Diseases) adverse event table. AHI was diagnosed at a median of 18 days after infection. Mean hemoglobin at enrollment of male participants was 14.8 g/dL, and for females, it was 13.0 g/dL. Over 48 weeks, there was a mean increase of 0.2 g/dL among men (P = 0.01) and a decrease of 0.7 g/dL among women (P = 0.03). The overall prevalence of anemia was low, with 7 (3.5%) of 202 fulfilling grade 1 or 2 anemia criteria. Anemia was rare after frequent phlebotomy in research participants with AHI, before and after antiretroviral therapy. Given that the blood volume drawn from this study did not pose substantial clinical risk, increasing the volume of blood drawn for research purposes in acute HIV-infected research participants could be considered for future studie

Corrigendum to ‘Decision making for invasive and non-invasive optional procedures within an acute HIV research cohort in Bangkok,’ [Contemporary Clinical Trials Communication (2023)101054](S2451865422001715)(10.1016/j.conctc.2022.101054)

The authors regret that Dr. Sandhya Vasan was missed in the author list for this article. The revised author order is as follows: Sinéad Isaacson1,2, Kristine Kuczynski1, Nuchanart Ormsby1, Holly L. Peay3, Stuart Rennie1,4, R. Jean Cadigan1,4, Eugène Kroon5, Nittaya Phanuphak 5, Jintanat Ananworanich6, Sandhya Vasan7,8, Thidarat Jupimai9, Peeriya Prueksakaew5, Gail E. Henderson1§ 1 Social Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 2 Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 3 RTI International, Research Triangle Park, Durham, North Carolina, USA. 4 Center for Bioethics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 5 SEARCH, Institute of HIV Research and Innovation, Bangkok, Thailand. 6 Department of Global Health, Amsterdam University Medical Centers, University of Amsterdam, and Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands. 7 US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA. 8 The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. 9 Center of Excellence in Pediatric Infectious Diseases and Vaccines Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. The authors regret that Acknowledgements omitted reference to cooperative agreements that funded this work, and the Disclaimer was omitted. The corrected versions are as follows

Immunological, Cognitive, and Psychiatric Outcomes After Initiating Efavirenz- and Dolutegravir-based Antiretroviral Therapy During Acute Human Immunodeficiency Virus Infection

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). Participants initiated 1 of 3 ART regimens during AHI: EFV-based (n = 131), DTG-based (n = 92), or DTG intensified with maraviroc (DTG/MVC, n = 35). All regimens included 2 nucleoside reverse-transcriptase inhibitors and were maintained for 96 weeks. CD4+ and CD8+ T-cell counts, mood symptoms, and composite score on a 4-test neuropsychological battery (NPZ-4) were compared. RESULTS: At baseline, the median age was 26 years, 99% were male, and 36% were enrolled during Fiebig stage I-II. Plasma viral suppression at weeks 24 and 96 was similar between the groups. Compared with the EFV group, the DTG group showed greater increments of CD4+ (P < .001) and CD8+ (P = .015) T-cell counts but a similar increment of CD4/CD8 ratio at week 96. NPZ-4 improvement was similar between the 2 groups at week 24 but greater in the DTG group at week 96 (P = .005). Depressive mood and distress symptoms based on the Patient Health Questionnaire and distress thermometer were similar between the 2 groups at follow-up. Findings for the DTG/MVC group were comparable to those for the DTG group vs the EFV group. CONCLUSIONS: Among individuals with AHI, 96 weeks of DTG-based ART was associated with greater increments of CD4+ and CD8+ T-cell counts and improvement in cognitive performance

Decision making for invasive and non-invasive optional procedures within an acute HIV research cohort in Bangkok

Clinical research regularly includes required, nontherapeutic procedures to answer research questions. Optional procedures usually offer minimal or no personal benefit and may involve harms and burdens.Members from the Bangkok SEARCH010/RV254 HIV research cohort of individuals acutely HIV-infected are recruited to six optional procedures varying in invasiveness: leukapheresis, genital secretions collection, lumbar puncture, brain MRI/MRS/DTI, colon biopsy, and lymph node biopsy. We surveyed cohort members about their first recruitment for each procedure to examine factors associated with decision making and attitudes about compensation.406 members (68%) completed the survey. Reported procedure participation ranged from 71% (MRI) to 27% (lymph node biopsy). Respondents underwent 0–6 procedure types (median 3). Ordinal regression indicated that lower perceived HIV impact and HIV remission trial participation were associated with more procedures completed. Reports of decision difficulty varied, and feeling pressured by research staff was low overall. Notably, those who declined procedures and those who underwent more invasive procedures reported greater decision difficulty and perceived pressure. Most respondents felt compensation amounts were appropriate, although opinions differed by procedure, and for some procedures, between people who agreed and declined.There is limited literature regarding consent to and attitudes about optional research procedures. Researchers must consider how to best support voluntary decisions for procedures with little personal benefit, particularly in lower-income or marginalized populations. In this longitudinal research cohort, perceived pressure to participate may be a concern, although our finding of variation in participation rates corresponding to invasiveness is reassuring. Data from different research contexts would provide important comparators

Feasibility and safety of research sigmoid colon biopsy in a cohort of Thai men who have sex with men with acute HIV-1

Background: The gut-associated lymphoid tissue (GALT) is a major reservoir of HIV-1 established early in acute HIV-1 infection (AHI). Sampling tissue from GALT can provide information about viral reservoirs and immune responses but may be complicated during AHIfor reasons such as high viral replication, CD4 T cell depletion and immune activation. Risk of adverse events (AEs) associated with research sigmoid colon biopsies was assessed in participants with AHIin Bangkok, Thailand. Methods: Between 2009 and 2016, 170 biopsies collected from the sigmoid colon were performed during AHIand at follow-up visits (median 24 weeks post AHIdiagnosis). Adverse event incidence was evaluated, as well as the associations of procedure timing, repetition and clinical parameters with AErisk. Negative binomial regression models were used to calculate incidence rate ratios and 95% confidence intervals. Results: Among 103 participants (median age of 27 years, 97.1% male, 96.1% men who have sex with men), 87 sigmoidoscopies were completed during AHIand 83 at a follow-up visit. Approximately 30 biopsies were obtained per procedure for assessment of colonic viral load and HIV-1 reservoir, immunohistochemistry or phenotypic assays. All 11 AEs were grade 1 (6.5%) and included abdominal discomfort (n = 5, 2.9%), mild rectal bleeding (n = 5, 2.9%) and difficulty passing stool (n = 1, 0.6%). Biopsy-related AErisk was not significantly associated with age, HIV-1 RNA, CD4 T cell count, or number and time of biopsy. Conclusions: Complications of sigmoidoscopy with biopsy in participants with AHIwere infrequent and mild. Longitudinal sampling of the sigmoid colon to evaluate the gut-associated HIV-1 reservoir can be safely performed as part of research studies

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

Switch to dolutegravir is well tolerated in Thais with HIV infection

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/m2 . 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