56 research outputs found

    Impact of multi-targeted antiretroviral treatment on gut T cell depletion and HIV reservoir seeding during acute HIV infection.

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    BackgroundLimited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy.Methods and findingsWe prospectively screened 24,430 subjects in Bangkok and identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II, 15 Fiebig III, 2 Fiebig IV) of whom 15 completed 24 weeks of megaHAART (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc). Sigmoid biopsies were completed in 24/30 at baseline and 13/15 at week 24. At baseline, the median age was 29 years and 83% were MSM. Most were symptomatic (87%), and were infected with R5-tropic (77%) CRF01_AE (70%). Median CD4 was 406 cells/mm(3). HIV RNA was 5.5 log(10) copies/ml. Median total blood HIV DNA was higher in Fiebig III (550 copy/10(6) PBMC) vs. Fiebig I (8 copy/10(6) PBMC) (p = 0.01) while the median %CD4+CCR5+ gut T cells was lower in Fiebig III (19%) vs. Fiebig I (59%) (p = 0.0008). After 24 weeks of megaHAART, HIV RNA levels of <50 copies were achieved in 14/15 in blood and 13/13 in gut. Total blood HIV DNA at week 0 predicted reservoir size at week 24 (p<0.001). Total HIV DNA declined significantly and was undetectable in 3 of 15 in blood and 3 of 7 in gut. Frequency of CD4+CCR5+ gut T cells increased from 41% at baseline to 64% at week 24 (p>0.050); subjects with less than 40% at baseline had a significant increase in CD4+CCR5+ T cells from baseline to week 24 (14% vs. 71%, p = 0.02).ConclusionsGut T cell depletion and HIV reservoir seeding increases with progression of AHI. MegaHAART was associated with immune restoration and reduced reservoir size. Our findings could inform research on strategies to achieve HIV drug-free remission

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

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    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

    A qualitative study of Thai HIV-positive young men who have sex with men and transgender women demonstrates the need for eHealth interventions to optimize the HIV care continuum

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    In Thailand, young men who have sex with men (YMSM) and transgender women (TG) are disproportionately affected by HIV and have suboptimal care continuum outcomes. Although Thai YMSM and young TG are early adopters of emerging technologies and have high Internet and technology access and utilization, the potential of technology has not been harnessed to optimize the HIV treatment cascade. We interviewed 18 behaviorally HIV-infected YMSM and young TG regarding care challenges, identified how eHealth could address care needs, and elicited preferences for eHealth interventions. Participants reported struggling with individual and societal-level stigma which negatively impacted linkage to and retention in care, and antiretroviral therapy adherence. YMSM and young TG described inadequate in-person support services and heavily relied on random online resources to fill information and support gaps, but sometimes viewed them as untrustworthy or inconsistent. Participants universally endorsed the development of eHealth resources and proposed how they could ameliorate individual-level fears over stigma and improve public perceptions about HIV. Personalized and integrated eHealth interventions with interactive, user-driven structures, credible content, rewards for engagement, real-time counseling and reminder support could help overcome barriers YMSM and young TG face in traditional HIV healthcare systems and have the potential to improve care outcome

    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

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    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

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

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    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
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