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Background: In rare cases, people living with chronic human immunodeficiency virus (HIV) infection do not develop antibodies despite demonstrable infection. Delayed or missed diagnosis of HIV infection leads to a lack of timely therapy, resulting in rapid disease progression with opportunistic infections or malignancies., Case Report: A 44-year-old Chinese man presented with sore throat, oral leukoplakia, fever, dyspnoea and diffuse ground glass-like lesions in both lungs. Serum cytomegalovirus DNA was detectable, and CD4 + T-cell count was low. The patient was suspected of being a person living with HIV despite of the repeatedly negative HIV antibody tests using enzyme-linked immunsorbent assay and Western blot. Subsequently, high-plasma HIV RNA viral load was found on two repeated tests, while HIV DNA was also positive. Thus, the patient was confirmed as presenting with HIV-seronegative acquired immunodeficiency syndrome (AIDS). The symptoms improved in response to effective anti-fungal and anti-retroviral therapy after diagnosis., Conclusion: This is the third reported case of an HIV-seronegative AIDS patient in China, which are also rarely reported globally. HIV nucleic acid testing is important to screen out HIV infection, especially in those who present with severe immunodeficiency but remain HIV serogenative.

Objectives: To evaluate the safety and efficacy of chidamide to reverse HIV-1 latency in vivo and to compare the effects of four clinically tested histone deacetylase (HDAC) inhibitors on non-histone proteins in vitro., Methods: Participants received chidamide orally at 10 mg twice weekly for 4 weeks while maintaining baseline antiretroviral therapy. The primary outcome was plasma viral rebound during chidamide dosing and the secondary outcomes were safety, pharmacokinetic and pharmacodynamic profiles, changes in cell-associated HIV-1 RNA and HIV-1 DNA, and immune parameters. Western blotting was used to compare the in vitro effects of the four HDAC inhibitors on HSP90, NF-κB and AP-1., Results: Seven aviraemic participants completed eight oral doses of chidamide, and only grade 1 adverse events were observed. Cyclic increases in histone acetylation were also detected. All participants showed robust and repeated plasma viral rebound (peak viraemia 147-3850 copies/mL), as well as increased cell-associated HIV-1 RNA, during chidamide treatment. Furthermore, we identified an enhanced HIV-1-specific cellular immune response and a modest 37.7% (95% CI: 12.7-62.8%, P = 0.028) reduction in cell-associated HIV-1 DNA. Compared with the other three HDAC inhibitors, chidamide had minimal cytotoxicity in vitro at clinically relevant concentrations and showed mechanistically superior effects on non-histone proteins, including HSP90, NF-κB and AP-1., Conclusions: Chidamide safely and vigorously disrupts HIV-1 latency in vivo, which makes it a promising latency-reversing agent., (© 2020 British HIV Association.)

Background: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs., Methods: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%., Results: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group., Conclusions: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure., Trial Registration: ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx., (Copyright © 2020 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Processing procedures for inducing domain size reduction and/or amorphous phase generation can be crucial for enhancing the bioavailability of active pharmaceutical ingredients (APIs). It is important to quantify these reduced coherence phases and to detect and characterize associated structural changes, to ensure that no deleterious effects on safety, function, or stability occur. Here, X-ray powder diffraction (XRPD), total scattering pair distribution function (TSPDF) analysis, and solid-state nuclear magnetic resonance spectroscopy (SSNMR) have been performed on samples of GSK2838232B, an investigational drug for the treatment of human immunodeficiency virus (HIV). Preparations were obtained through different mechanical treatments resulting in varying extents of domain size reduction and amorphous phase generation. Completely amorphous formulations could be prepared by milling and microfluidic injection processes. Microfluidic injection was shown to result in a different local structure due to dispersion with dichloromethane (DCM). Implications of combined TSPDF and SSNMR studies to characterize molecular compounds are also discussed, in particular, the possibility to obtain a thorough structural understanding of disordered samples from different processes.

Objectives: The aim of this study was to compare the effect of 2 y of antiretroviral therapy (ART) on the percentage of activated CD38⁺CD8⁺ T cells and human leukocyte antigen (HLA)-DR⁺CD8⁺ T cells, and the expression of the co-stimulatory molecule CD28 on CD4⁺ and CD8⁺ T cells in the peripheral blood of HIV-infected adults, and to assess the use of immune activation markers to predict the virological response to ART in a cohort of HIV-1-infected patients in the north-western part of China., Methods: We analyzed changes in the CD4⁺ T cell count, viral load, and the percentages of CD38⁺CD8⁺ T cells, HLA-DR⁺CD8⁺ T cells, CD28⁺CD4⁺ T cells, and CD28⁺CD8⁺ T cells in 48 patients with HIV diseases during 2 y of suppressive highly active antiretroviral therapy (HAART). Good virological responders (n = 20) were defined as those who had suppressed and maintained a plasma viral load below the detection limit of the assay for at least 12 months. Poor virological responders (n = 28) were defined as those with a detectable viral load at 6 and 12 months after beginning HAART., Results: Among the 20 good responders, baseline median levels of CD38⁺CD8⁺ T cells were elevated, but had decreased significantly at 24 months of therapy (p < 0.0001). Median levels of HLA-DR⁺CD8⁺ T cells also decreased at 24 months of therapy (p < 0.0001). Levels of expression of CD28⁺CD4⁺ T cells rose steadily to 6 months (p = 0.03), and smoothly reached levels observed among HIV-negative blood donors during the 24 months of therapy (p > 0.05). Levels of expression of CD28⁺CD8⁺ T cells increased at 24 months (p = 0.04). Among the 28 poor responders, median levels of CD38⁺CD8⁺ T cells decreased significantly at 24 months (p < 0.0001). Levels of HLA-DR⁺CD8⁺ T cells also decreased at 24 months (p < 0.001). Levels of CD28⁺CD8⁺ T cells and levels of CD28⁺CD4⁺ T cells increased at 24 months remained unchanged. The percentage of CD38⁺CD8⁺ T cells appeared to provide a sensitive estimate of the overall immune recovery in comparison with the percentage of HLA-DR⁺CD8⁺ T cells, although this lacked specificity for the determination of early virological drug failure and did not appear to be a reliable surrogate for RNA viral load., Conclusions: We show that HAART can be used successfully in Chinese populations with elevated baseline immune activation markers and that the percentage of CD38⁺CD8⁺ T cells may be an additional parameter to the current criteria for estimating the antiretroviral response with HAART.

Individuals with a human immunodeficiency virus (HIV) infection are at higher risk of developing adverse drug reactions. Multiple drugs are usually prescribed to patients with HIV infection for preventing the replication of HIV and for the treatment of the associated opportunistic infections. We report here the first case of an HIV-1-infected patient who developed an exfoliative dermatitis induced by efavirenz, a non-nucleoside reverse transcriptase inhibitor. Physicians should be aware of the possible occurrence of efavirenz-induced skin eruptions from the start of antiviral treatment of HIV infection.