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Journal of AIDS & Clinical Research

ISSN: 2155-6113

Open Access

Current Issue

Volume 11, Issue 12 (2020)

    Review Article Pages: 1 - 7

    A 35-Year Review of Pre-Clinical HIV Therapeutics Research Reported by NIH ChemDB: Influences of Target Discoveries, Drug Approvals and Research Funding

    Shawn S. Jackson, Louise E. Sumner, Mikaela A. Finnegan, Emily A. Billings, Danna L. Huffman and Margaret A. Rush*

    We present a retrospective analysis of trends in human immunodeficiency virus (HIV) small molecule drug development over the last thirty-five years based on data captured by ChemDB, a United States (US) National Institutes of Health (NIH) database of chemical and biological HIV testing data. These data are analyzed alongside NIH funding levels, US Food and Drug Administration (FDA) drug approvals, and new target identifications to explore the influences of these factors on anti-HIV drug discovery research. The NIH’s ChemDB database collects chemical and biological testing data describing published and patented pre-clinical compounds in development as potential HIV therapeutics. These data were used as a proxy for estimating overall levels of HIV therapeutics research activities in order to assess research trends. Data extracted from ChemDB were compared with records of drug approvals from the FDA, NIH funding levels, and drug target discoveries to elucidate the influences that these factors have on levels of HIV therapeutics research activities. Despite the increasingly wide suite of HIV therapeutic options that have accumulated during decades of research, interest in HIV therapeutics research activities remains strong. While decreases in research activity levels have followed cuts in research funding, FDA-approved HIV therapeutics have continued to accumulate. The comparisons presented here indicate that HIV drug research activity levels have historically been more responsive to changes in funding levels and the identification of new drug targets, than they have been to drug approvals. Continued interest in HIV therapeutics research may reflect that fact that of the 54 drugs approved for HIV treatment as of 2018, only six inhibitory targets are represented. Moreover, drug resistance presents substantial clinical challenges. Sustained research interest despite drug approvals and fluctuations in available funding likely reflects the clinical need for safer, more palatable and more efficacious therapeutics; robust attention to both novel therapeutics and inhibitory targets is necessary given the speed of development of drug-resistant HIV strains. Only with such continued interest will we reduce the burden of acquired immunodeficiency syndrome (AIDS) disease and control the AIDS epidemic.

    Research Article Pages: 1 - 5

    Computer-Assisted Speech Perception Assessment (CASPA) Data in Adults with and without HIV

    Peter Torre III1#, Gayle Springer2, Christopher Cox2, Howard J. Hoffman3, Abigail Fellows4, Jay Buckey Jr4 and Michael Plankey5

    Objective: There is increasing literature on the association of HIV disease with hearing loss in adults, although only very limited research regarding
    communication, specifically in a background noise condition. The purpose of this study was to first, evaluate computer-assisted speech perception
    assessment (CASPA) data among adults living with HIV (ALHIV) and adults living without HIV (ALwoHIV). And second, to examine the association
    of HIV disease variables and HIV treatment with CASPA measures among ALHIV.
    Methods: A sample of 101 ALHIV (n=57) and ALwoHIV (n=44) participants from the Baltimore-Washington DC site of the Multicenter AIDS Cohort
    Study (MACS) and the Washington DC site of the Women’s Interagency HIV Study (WIHS) completed CASPA testing. Testing was performed in
    sound treated rooms using a speaker placed 3 ft away from the listener.
    Results: ALHIV and ALwoHIV had similar mean thresholds for phoneme and consonant scoring. ALHIV had poorer phoneme and consonant
    thresholds despite better ear 4 kHz thresholds compared to the ALwoHIV, suggesting difficulty with detecting speech-in-noise not related to
    diminished pure-tone thresholds. In ALHIV only, after adjusting for age, sex, nadir CD4+ T-cell count, and better ear 4 kHz threshold, total time on
    protease inhibitors (PIs) was significantly negatively associated with both phoneme threshold and consonant threshold, while total time on nonnucleoside
    reverse transcriptase inhibitors (NNRTIs) was marginally associated with both threshold measures.
    Conclusion: CASPA performance appeared to be poorer in ALHIV and these results suggest that HIV treatment (i.e., cumulative PI or NNRTI use)
    may preserve speech communication abilities in noise.

    Research Article Pages: 1 - 9

    Tenofovir Disoproxil Fumarate-Lowering Lipid Effects Moderately Protect Liver during Long-Term Antiretroviral Therapy in HIV-Infected Patients

    Lijuan Ouyang#, Zhong Si Hong#, Wen Xiao Dong, Hong Qiong Zhu, Ying Li and Xiao Mou Peng*

    Background: Non-alcoholic fatty liver disease is prevalent in HIV-infected patients and dyslipidemia is the main cause of long-term toxicities of
    current antiretroviral therapy (ART). Tenofovir disoproxil fumarate (TDF) is a commonest antiretroviral of ART. It has been reported to have lipidlowering
    effects.
    Objectives: In this study, the influences of the lipid-lowering effects of TDF on fatty liver, liver function profiles and renal toxicity were further
    investigated in mono-HIV-infected patients during long-term ART up to five years.
    Methods: 115 and 38 HIV-infected, ART-naive patients who respectively received TDF- and zidovudine (AZT)-based regimens for 5 years were
    enrolled. The differences in lipid profiles, liver functions and renal toxicity between those two groups of patients and the correlations among these
    observed indicators were retrospectively analyzed.
    Results: After 5 years of ART, no increase in plasma triglyceride (TG) and only moderate increase in total cholesterol (TC) were found in TDF
    group. As for plasma TG and TC, the increments in the fifth year and the level changes over time in TDF group were all much less serious than
    those in AZT group. The new occurrence rates of hypercholesterolemia, fatty liver and abnormality of alanine aminotransferase (ALT) were
    significantly lower in TDF group. The mean estimated glomerular filtration rate (eGFR) was comparable between two groups except 4 patients who
    were excluded due to renal toxicity in TDF group. The further analyses showed that there were close correlations between TG and BMI, BMI and
    ALT, TC and ALT, and TC and AST, but no correlations between eGFR and TG or TC in patients treated with TDF-based regimen.
    Conclusion: The lipid-lowering effect of TDF had moderate protective effects on liver functions via reducing liver fat. In the era of tenofovir
    alafenamide fumarate and integrase inhibitors, TDF-based regimens may remain to be the first choice for young HIV-infection patients with
    dyslipidemia, fatty liver and obesity

    Research Pages: 1 - 5

    Development of the Malay Version of the English HIV Stigma Questionnaire: A Review

    Mohd Shaiful Azlan Bin Kassim*, Nor Asiah Muhammad, Muhd Hafizuddin Taufik bin Ramli, Azlinda Azman, Mohd Hazrin Hasim Hashim, Hanif bin Bistari, Fazila Haryati binti Ahmad, Nik Adilah Binti Shahein, Muhammad Solihin bin Rezali, Chan Ying Ying, Norhafizah Binti Sahril, Nor Ain Bt Ab Wahab, Mohd Hatta Bin Abd Mutalip and Noor Ani binti Ahmad

    Background: HIV Stigma impeded the screening, treatment and compliance of HIV/AIDS management. Therefore, the data on the burden of HIV stigma is vital. This study aims to examine the cross-cultural translation adaption of the Malay version of HIV Stigma Questionnaires and also examine its validity and reliability.

    Literature Review: The standard English version of the HIV Stigma Questionnaire by The Global Stigma and Discrimination Indicator Working Group (GSDIWG) and STRIVE research consortium was undergone a Malay translation via forward-backward methods. Content validity by the expert committees and reliability by preliminary pilot testing was done.

    Results: The content validity was approved by the expert committees with acceptable reliability during the preliminary survey analysis. Internal consistency was acceptable with Cronbach’s alpha value was 0.76.

    Conclusion: The validation of the Malay version of HIV Stigma questionnaire reveals an excellent cross-cultural adaption, content validation and reliability. This Malay version is open for potential Malaysia’s HIV Stigma studies in the future in parallel with our national strategic planning on HIV to end HIV by 2030.

    Brief Report Pages: 1 - 5

    Macrocytosis associated with lamivudine and emtricitabine use in patients with HIV

    Clemency Nye

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    Objectives: The aim of the study was to evaluate the effect of lamivudine on the erythrocyte mean corpuscular volume. Methods: We conducted a retrospective evaluation of the mean corpuscular volume in patients prescribed lamivudine, and a comparison group of patients not taking lamivudine or other NRTIs known to affect the MCV, using electronic patient records from a single UK centre. Results: A total of 456 patients whilst on lamivudine were compared to 483 patients not having taken lamivudine. The mean MCV in the lamivudine group was 94.1 (83-100fl)., which was statistically significantly higher than that in patients not taking lamivudine, 91.6 fl, including those taking emtricitabine (p-value < 0.0001). Of patients prescribed lamivudine, 49 (10%) developed a clinically significant macrocytosis, with an odds ratio for macrocytosis of 3.3 compared to patients not taking lamivudine. The effect of lamivudine on MCV was independent of patient age, sex, ethnicity, weight, dose of lamivudine or duration of therapy with lamivudine. A similar, but lesser, effect was seen with emtricitabine. Conclusions: This study suggests that lamivudine causes an increase in the mean corpuscular volume of erythrocytes, and that this is sufficient to cause a clinical macrocytosis in 10% of patients. This is of clinical relevance for practitioners managing patients prescribed lamivudine, in guiding the need for investigating macrocytosis.

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