Hyperlipidaemia in HIV-infected patients on lopinavir/ritonavir monotherapy in resource-limited settings

Cardiovascular disease (CVD) is an emerging concern for HIV-infected patients. Hyperlipidemia is a risk factor for CVD and a complication of protease-inhibitor-based antiretroviral therapy, but little is known about its incidence and risk factors in treated patients in resource-limited settings (RLS)

Deep Sequencing Reveals Compartmentalized HIV-1 in the Semen of Men with and without Sexually Transmitted Infection-Associated Urethritis

Concurrent sexually transmitted infections (STI) can increase the probability of HIV-1 transmission primarily by increasing the viral load present in semen. In this study, we explored the relationship of HIV-1 in blood and seminal plasma in the presence and absence of urethritis and after treatment of the concurrent STI. Primer ID deep sequencing of the V1/V3 region of the HIV-1 env gene was done for paired blood and semen samples from antiretroviral therapy (ART)-naive men living in Malawi with (n = 19) and without (n - 5) STI-associated urethritis; for a subset of samples, full-length env genes were generated for sequence analysis and to test entry phenotype. Cytokine concentrations in the blood and semen were also measured, and a reduction in the levels of proinflammatory cytokines was observed following STI treatment. We observed no difference in the prevalence of diverse compartmentalized semen-derived lineages in men with or without STI-associated urethritis, and these viral populations were largely stable during STI treatment. Clonal amplification of one or a few viral sequences accounted for nearly 50% of the viral population, indicating a recent bottleneck followed by limited viral replication. We conclude that the male genital tract is a site where virus can be brought in from the blood, where localized sustained replication can occur, and where specific genotypes can be amplified, perhaps initially by cellular proliferation but further by limited viral replication. IMPORTANCE HIV-1 infection is a sexually transmitted infection that coexists with other STI. Here, we examined the impact of a concurrent STI resulting in urethritis on the HIV-1 population within the male genital tract. We found that viral populations remain largely stable even with treatment of the STI. These results show that viral populations within the male genital tract are defined by factors beyond transient inflammation associated with a concurrent STI

Discontinuation of tenofovir disoproxil fumarate from initial ART regimens because of renal adverse events: An analysis of data from four multi-country clinical trials

Tenofovir disoproxil fumarate (TDF), a potent and commonly used antiretroviral drug, is associated with renal tubular dysfunction and renal adverse events. We evaluated the frequency of, time to, and baseline risk factors for discontinuing TDF from initial antiretroviral therapy (ART) regimens because of renal adverse events from presumed tenofovir renal toxicity. We conducted an observational cohort study as a secondary analysis of data from four clinical trials conducted mainly in low- and middle-income countries. We included ART naïve participants living with HIV who started TDF-containing ART regimens in the trials. Participants had to have estimated creatinine clearance (eCrCl) equal to or greater than 60ml/min before starting ART. The primary outcome was the first instance of discontinuing TDF because of renal adverse events attributed to tenofovir renal toxicity during the first 48 weeks after starting ART. We evaluated the cumulative incidence of discontinuing TDF and associated risk factors using Fine and Gray competing risk regression models with a backward elimination variable selection strategy. There were 2802 ART-naïve participants who started TDF-containing ART from the four clinical trials were included in the analysis. Fifty-eight percent were female, the median age was 34 years, and 87% had CD4 cell counts less than 200 cells/μl. Sixty-four participants (2.4%, 95% CI 1.7%-2.8%) discontinued TDF due to renal adverse events. Among the 64 participants, the median time to discontinue TDF was 9.4 weeks (IQR: 3.4–20.7 weeks). From multivariable Fine and Gray regression models, risk factors for discontinuing TDF were older age, CD4 cell count <200 cells/μl, presence and severity of anemia, and eCrCl <90 ml/min. The risk of discontinuing TDF because of renal adverse events was low in participants initiating TDF-containing ART with advanced HIV and normal renal function, attesting to the tolerability of TDF in ART in low- and middle-income countries

Gentamicin Susceptibility in Neisseria gonorrhoeae and Treatment Outcomes for Urogenital Gonorrhea After 25 Years of Sustained Gentamicin Use in Malawi

Background Gentamicin has been used for the treatment of gonorrhea in Malawi since 1993. However, declining clinical cure rates have been suspected. We evaluated current Neisseria gonorrhoeae susceptibility to gentamicin in vitro and clinically. Methods Men with acute urethritis were recruited at the Bwaila District Hospital STI Clinic in Lilongwe, Malawi, between January 2017 and August 2019. All men provided urethral swabs for etiological testing at enrollment and test of cure (TOC), 1 week later, using Gram-stained microscopy and culture. We used Etest to determine minimum inhibitory concentrations (MICs) of gentamicin, azithromycin, cefixime, ceftriaxone, ciprofloxacin, and spectinomycin; disc diffusion for tetracycline susceptibility; and whole-genome sequencing (WGS) to verify/refute treatment failure. Results Among 183 N. gonorrhoeae culture-positive men enrolled, 151 (82.5%) had a swab taken for TOC. Of these 151 men, 16 (10.6%) had a positive culture at TOC. One hundred forty-one baseline isolates were tested for gentamicin susceptibility using Etest: 2 (1.4%), MIC = 2 μg/mL; 111 (78.7%), MIC = 4 μg/mL; and 28 (19.9%), MIC = 8 μg/mL. All isolates were susceptible to azithromycin, cefixime, ceftriaxone, and spectinomycin, whereas 63.1% had intermediate susceptibility or resistance to ciprofloxacin. Almost all (96.1%) isolates were resistant to tetracycline. All examined isolates cultured at TOC (n = 13) had gentamicin MICs ≤8 μg/mL. Ten men had pretreatment and posttreatment isolates examined by whole-genome sequencing; 2 (20%) were verified new infections (4119 and 1272 single-nucleotide polymorphisms), whereas 8 (80%) were confirmed treatment failures (0-1 single-nucleotide polymorphism). Conclusions Gentamicin MICs poorly predict gonorrhea treatment outcome with gentamicin, and treatment failures are verified with gonococcal strains with in vitro susceptibility to gentamicin. The first-line treatment of gonorrhea in Malawi should be reassessed

High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny

Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modeling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged β-sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles

Combining In Situ Techniques XRD, IR, and C 13 NMR and Gas Adsorption Measurements Reveals CO2 Induced Structural Transitions and High CO2 CH4 Selectivity for a Flexible Metal Organic Framework JUK 8

Flexible metal organic frameworks MOFs are promising materials in gas related technologies. Adjusting the material to processes requires understanding of the flexibility mechanism and its influence on the adsorption properties. Herein, we present the mechanistic understanding of CO2 induced pore opening transitions of the water stable MOF JUK 8 [Zn oba pip ]n, oba2 4,4 amp; 8242; oxybis benzenedicarboxylate , pip 4 pyridyl functionalized benzene 1,3 dicarbohydrazide as well as its potential applicability in gas purification. Detailed insights into the global structural transformation and subtle local MOF adsorbate interactions are obtained by three in situ techniques XRD, IR, and 13CO2 NMR . These results are further supported by single crystal X ray diffraction SC XRD analysis of the solvated and guest free phases. High selectivity toward carbon dioxide derived from the single gas adsorption experiments of CO2 195 and 298 K , Ar 84 K , O2 90 K , N2 77 K , and CH4 298 K is confirmed by high pressure coadsorption experiments of the CO2 CH4 75 25 v v mixture at different temperatures 288, 293, and 298 K and in situ NMR studies of the coadsorption of 13CO2 13CH4 50 50 v v; 195

Electronic Devices Using Open Framework Materials

Open framework materials (OFM) constitute a large and growing class of nanoporous crystalline structures that is attracting considerable attention for electronic device applications. This review summarizes the most recent reports concerning electronic devices enabled by either of the two primary categories of OFM, metal–organic frameworks (MOFs) and covalent–organic frameworks (COFs). Devices in which the OFM plays an active role (as opposed to acting only as a selective sorbent or filter) are the principal focus, with examples cited that include field-effect transistors, capacitors, memristors, and a wide variety of sensing architectures. As a brief tutorial, we also provide a concise summary of various methods of depositing or growing OFM on surfaces, as these are of crucial importance to the deployment of electronic OFM. Finally, we offer our perspective concerning future research directions, particularly regarding what in our view are the biggest challenges remaining to be addressed. On the basis of the literature discussed here, we conclude that OFM constitute a unique class of electronic materials with characteristics and advantages that are distinct from either conventional inorganic semiconductors or organic conductors. This suggests a bright future for these materials in applications such as edge computing, resistive switching, and mechanically flexible sensing and electronics