Predictors of First-Time and Repeat HIV Testing Among HIV-Positive Individuals in Kenya
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
Authors: De Anda, Sofia; Njoroge, Anne; Njuguna, Irene; Dunbar, Matthew D.; Abuna, Felix; Macharia, Paul; Betz, Bourke; Cherutich, Peter; Bukusi, David; Farquhar, Carey; Katz, David A.
Background: Despite a doubling of HIV testing coverage in Kenya over the past decade, approximately 2 in 10 people with HIV remained unaware of their infection in 2018. HIV testing is most effective in identifying people with undiagnosed HIV through frequent and strategic testing in populations at high risk. An assessment of testing frequency and predictors of first-time and repeat testing is critical for monitoring effectiveness of testing strategies. Methods: We conducted a cross-sectional analysis of adults aged >= 18 years who tested HIV-positive at 4 HIV testing and counseling clinics in Kenya from February 2015 to February 2016. We categorized individuals based on testing history, used Wilcoxon rank-sum tests to assess differences in intervals between the most recent and current HIV test, and used log-binomial regression to determine characteristics associated with first-time and repeat testing. Results: Among 1136 people testing HIV-positive, 336 (30%) had never tested before and 800 (70%) had, of whom 208 (26%) had previously tested positive. Among previously negative repeat testers, the median intertest interval was 414 days in key/priority populations (interquartile range = 179-1072) vs. 538 in the general population (interquartile range = 228-1299) (P = 0.09). Compared with previously negative repeat testers, being a first-time tester was associated with being age >= 40 years [vs. 18-24; adjusted risk ratio = 1.67, 95% confidence interval (CI): 1.23 to 2.26], men (vs. women; adjusted risk ratio = 1.45, 95% CI: 1.21 to 1.71), and testing through provider-initiated testing and counseling (vs. client initiated; 1.19, 95% CI: 1.00 to 1.40). Conclusions: There is a need to increase HIV testing among older individuals and men, increase testing frequency in key/priority populations, and maintain provider-initiated and facility-based testing to reach first-time testers.
Targeting dual tolerant regions of binding pocket: Discovery of novel morpholine-substituted diarylpyrimidines as potent HIV-1 NNRTIs with significantly improved water solubility
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Authors: Wang, Zhao; Kang, Dongwei; Feng, Da; Cherukupalli, Srinivasulu; Jiang, Xiangyi; Fu, Zhipeng; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong; Zhan, Peng
To address the intractable issues of drug resistance and poor solubility, a novel series of morpholine-substituted diarylpyrimidines targeting the tolerant region I and tolerant region II of NNIBP were rationally designed by utilizing the available crystallography studies. The biological evaluation results showed that four most promising compounds (14e1, 14g1, 14g2 and 14j2) displayed excellent potency against WT HIV-1 strain with EC(50 )values ranging from 58 to 87 nM, being far more potent than NVP and comparable to ETV. Besides, some derivatives exhibited moderate activity in inhibiting the mutant HIV-1 strains. More encouragingly, 14d2 (RF = 0.4) possessed higher antiresistance profile than ETV (RF = 6.3) and K-5a2 (RF = 3.0) toward the double mutant strain F227L + V106A. The HIV-1 RT inhibition assay confirmed their binding target. The molecular docking studies were conducted and discussed in detail to rationalize the preliminary SARs. Further test indicated that morpholine could indeed promote the improvement of water solubility. Additionally, the in silico prediction of physicochemical properties and CYP enzymatic inhibitory ability were investigated to evaluate their drug-like features. (C) 2020 Elsevier Masson SAS. All rights reserved.