Jintanat Ananworanich

International AIDS Society global scientific strategy: towards an HIV cure 2016

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the groups strategy.

HIV DNA Set Point is Rapidly Established in Acute HIV Infection and Dramatically Reduced by Early ART

HIV DNA is a marker of HIV persistence that predicts HIV progression and remission, but its kinetics in early acute HIV infection (AHI) is poorly understood. We longitudinally measured the frequency of peripheral blood mononuclear cells harboring total and integrated HIV DNA in 19 untreated and 71 treated AHI participants, for whom 50 were in the earliest Fiebig I/II (HIV IgM −) stage, that is ≤ 2 weeks from infection. Without antiretroviral therapy (ART), HIV DNA peaked at 2 weeks after enrollment, reaching a set-point 2 weeks later with little change thereafter. There was a marked divergence of HIV DNA values between the untreated and treated groups that occurred within the first 2 weeks of ART and increased with time. ART reduced total HIV DNA levels by 20-fold after 2 weeks and 316-fold after 3 years. Therefore, very early ART offers the opportunity to significantly reduce the frequency of cells harboring HIV DNA.

Persistent, Albeit Reduced, Chronic Inflammation in Persons Starting Antiretroviral Therapy in Acute HIV Infection

Background. u2003Serious non-AIDS events cause substantial disease and death despite human immunodeficiency virus (HIV) suppression with antiretroviral therapy (ART). Biomarkers of inflammation, coagulation cascade activation, and fibrosis predict these end-organ events. We aimed to determine whether ART initiation during acute HIV infection would attenuate changes in these biomarker levels. Methods. u2003Plasma samples were obtained from participants starting ART during acute or chronic HIV infection and from HIV-uninfected participants from Bangkok, Thailand. Biomarkers of inflammation (C-reactive protein [CRP], interleukin 6, soluble interleukin 6 receptor [sIL-6R], soluble gp130, tumor necrosis factor [TNF]), enterocyte turnover (intestinal fatty acid binding protein [I-FABP]), lipopolysaccharide-induced monocyte activation (soluble CD14 [sCD14]), coagulation cascade activation [D-dimer], and fibrosis (hyaluronic acid [HA]) were measured at baseline and through 96 weeks of ART. Results. u2003CRP, TNF, sIL-6R, I-FABP, sCD14, D-dimer, and HA levels were elevated in acute HIV infection. Early ART was associated with increased I-FABP levels but normalization of TNF, sIL-6R, and D-dimer levels. CRP, sCD14, and HA levels decreased during ART but remained elevated compared with HIV-uninfected participants. Higher sCD14, CRP, and D-dimer levels were associated with higher peripheral blood mononuclear cell and gut integrated HIV DNA levels. Decreases in sCD14 and CRP levels were correlated with increases in CD4 T-cell counts. Conclusions. u2003ART initiated in early acute HIV infection was associated with normalization of the coagulation cascade and several systemic inflammatory biomarkers, but the acute-phase response, enterocyte turnover, monocyte activation, and fibrosis biomarkers remained elevated. Additional interventions to attenuate inflammation may be needed to optimize clinical outcomes in persons with HIV infection.

Hidden drug resistant HIV to emerge in the era of universal treatment access in Southeast Asia.

Background Universal access to first-line antiretroviral therapy (ART) for HIV infection is becoming more of a reality in most low and middle income countries in Asia. However, second-line therapies are relatively scarce. Methods and Findings We developed a mathematical model of an HIV epidemic in a Southeast Asian setting and used it to forecast the impact of treatment plans, without second-line options, on the potential degree of acquisition and transmission of drug resistant HIV strains. We show that after 10 years of universal treatment access, up to 20% of treatment-naïve individuals with HIV may have drug-resistant strains but it depends on the relative fitness of viral strains. Conclusions If viral load testing of people on ART is carried out on a yearly basis and virological failure leads to effective second-line therapy, then transmitted drug resistance could be reduced by 80%. Greater efforts are required for minimizing first-line failure, to detect virological failure earlier, and to procure access to second-line therapies.

Scaling up of HIV treatment for men who have sex with men in Bangkok: a modelling and costing study.

BACKGROUNDnDespite the high prevalence of HIV in men who have sex with men (MSM) in Bangkok, little investment in HIV prevention for MSM has been made. HIV testing and treatment coverage remains low. Through a pragmatic programme-planning approach, we assess possible service linkage and provision of HIV testing and antiretroviral treatment (ART) to MSM in Bangkok, and the most cost-effective scale-up strategy.nnnMETHODSnWe obtained epidemiological and service capacity data from the Thai National Health Security Office database for 2011. We surveyed 13 representative medical facilities for detailed operational costs of HIV-related services for sexually active MSM (defined as having sex with men in the past 12 months) in metropolitan Bangkok. We estimated the costs of various ART scale-up scenarios, accounting for geographical accessibility across Bangkok. We used an HIV transmission population-based model to assess the cost-effectiveness of the scenarios.nnnFINDINGSnFor present HIV testing (23% [95% CI 17-36] of MSM at high risk in 2011) and ART provision (20% of treatment-eligible MSM at high risk on ART in 2011) to be sustained, a US

Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection

73·8 million (

Clinical and public health implications of acute and early HIV detection and treatment: a scoping review

51·0 million to

Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences

97·0 million) investment during the next decade would be needed, which would link an extra 43,000 (27,900-58,000) MSM at high risk to HIV testing and 5100 (3500-6700) to ART, achieving an ART coverage of 44% for MSM at high risk in 2022. An additional

Integrin α4β7 expression on peripheral blood CD4+ T cells predicts HIV acquisition and disease progression outcomes.

55·3 million investment would link an extra 46,700 (30,300-63,200) MSM to HIV testing and 12,600 (8800-16,600) to ART, achieving universal ART coverage of this population by 2022. This increased investment is achievable within present infrastructure capacity. Consequently, an estimated 5100 (3600-6700) HIV-related deaths and 3700 (2600-4900) new infections could be averted in MSM by 2022, corresponding to a 53% reduction in deaths and a 35% reduction in infections from 2012 levels. The expansion would cost an estimated

Delayed differentiation of potent effector CD8+ T cells reducing viremia and reservoir seeding in acute HIV infection

10,809 (9071-13,274) for each HIV-related death,