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ObjectivesIdentify factors (demographic and clinical) associated with a non-suppressed viral load (VL) of people living with HIV (PLHIV) on antiretroviral therapy (ART) in Nigeria.DesignCross-sectional study.SettingSixteen US Agency for International Development supported states in Nigeria.Participants585 632 PLHIV on ART.Primary outcome measuresVL non-suppression (defined as having a VL of at least 1000 HIV RNA copies per mL of plasma). χ2testing and multivariable modified Poisson regression with robust variance estimates were conducted on routinely collected ART programme data.ResultsSixty-six per cent of the study population were females. The largest age groups were 25–34 and 35–44, accounting for 32.1% and 31.1%, respectively. Males had a 9% greater likelihood (adjusted prevalence ratio, APR=1.09) of being non-suppressed. The age groups below 60+ (APR=0.67) had a higher likelihood of a non-suppressed VL, with the highest in the 0–14 age group (APR=2.38). Clients enrolled at tertiary and secondary level facilities had the greatest likelihood of a non-suppressed VL. Clients who started ART between 2010 and 2015 had the greatest likelihood of viral non-suppression (APR=6.19). A shorter time on ART (ConclusionsTargeting males, clients of younger age, those on treatment for less than 3 years, clients at tertiary and secondary health facilities, small and medium facilities, and clients in the Edo, Niger and Borno states for interventions could lead to improvements in VL suppression in Nigeria. The independent factors associated with a non-suppressed VL can guide improvements in ART programme development and VL suppression of PLHIV on ART in Nigeria.

Dichapetalum cymosum produces the toxic fluorinated metabolite, fluoroacetate, presumably as a defence mechanism. Given the rarity of fluorinated metabolites in nature, the biosynthetic origin and function of fluoroacetate have been of particular interest. However, the mechanism for fluorination in D. cymosum was never elucidated. More importantly, there is a severe lack in knowledge on a genetic level for fluorometabolite-producing plants, impeding research on the subject. Here, we report on the first transcriptome for D. cymosum and investigate the wound response for insights into fluorometabolite production. Mechanical wounding studies were performed and libraries of the unwounded (control) and wounded (30 and 60 min post wounding) plant were sequenced using the Illumina HiSeq platform. A combined reference assembly generated 77,845 transcripts. Using the SwissProt, TrEMBL, GO, eggNOG, KEGG, Pfam, EC and PlantTFDB databases, a 69% annotation rate was achieved. Differential expression analysis revealed the regulation of 364 genes in response to wounding. The wound responses in D. cymosum included key mechanisms relating to signalling cascades, phytohormone regulation, transcription factors and defence-related secondary metabolites. However, the role of fluoroacetate in inducible wound responses remains unclear. Bacterial fluorinases were searched against the D. cymosum transcriptome but transcripts with homology were not detected suggesting the presence of a potentially different fluorinating enzyme in plants. Nevertheless, the transcriptome produced in this study significantly increases genetic resources available for D. cymosum and will assist with future research into fluorometabolite-producing plants.

Hydroxynitrile lyases (HNLs) are sought-after, stereo-selective biocatalysts used in the agrochemical, pharmaceutical and fine chemical industries to produce cyanohydrin enantiomers. There ...

Background Human immunodeficiency virus (HIV) is untransmissible when the viral load (VL) is undetectable, underscoring the importance of achieving VL suppression for HIV epidemic control. It is estimated that 78% of people living with HIV (PLHIV) on antiretroviral therapy (ART) in Nigeria are virally suppressed. The need to improve VL suppression rates raises questions about the factors associated with an unsuppressed VL, which this study explored using a large cross-sectional database of clients who received ART over a period of 20 years. Methods Data from 517,012 clients with a documented VL were analyzed using univariate and adjusted multivariate logistic regression. The independent variables investigated were sex, age group, facility type, time on ART until last VL test, multi-month dispensing (MMD), and geopolitical zone. To verify model improvement by variable, we performed backward elimination for the logistic regression model. Results Sixty-six percent of the study population were females. The largest age groups were 35–44 and 25–34, accounting for 32% and 31%, respectively. The greatest adjusted odds for an unsuppressed VL were associated with shorter duration MMD prescriptions of 1–2 months (adjusted odds ratio [AOR]=14.05) and 3 months (AOR=3.13). Males had 8% greater odds (AOR=1.08) of being unsuppressed. The age groups below the 45–59 age group (AOR=0.84) had higher odds of having an unsuppressed VL, with the highest odds in the 0–14 age group (AOR=1.87). Clients enrolled at tertiary and secondary level facilities had the greatest odds of having an unsuppressed VL. A shorter time on ART until the last VL (1–3 years [AOR=1.14]) was associated with a higher risk of an unsuppressed VL. Clients in the North-Central (AOR=1.83) and North-East (AOR=1.49) zones had the greatest odds of viral non-suppression. Conclusions Enabling the provision of 3+ months of MMD to PLHIV and targeting younger age groups, tertiary and secondary health facilities, small and medium facilities, and the North-Central and North-East zones for interventions could lead to improvements in VL suppression in Nigeria. The independent factors associated with an unsuppressed VL can guide improvements in ART program development and VL suppression of PLHIV in Nigeria.

Background Patient interruption of antiretroviral therapy (ART) continues to limit HIV programs’ progress toward epidemic control. Multiple factors have been associated with client interruption in treatment (IIT)— including age, gender, CD4 count, and education level. In this paper, we explore the factors associated with IIT in people living with HIV (PLHIV) in United States Agency for International Development (USAID)-supported facilities under the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) program in Nigeria. Methods We conducted cross-sectional analyses on data obtained from Nigeria’s National Data Repository (NDR), representing a summarized record of 573 630 ART clients that received care at 484 PEPFAR/USAID-supported facilities in 16 states from 2000–2020. IIT was defined as no clinical contact for 28 days or more after the last expected clinical contact. Univariate and multivariate logistic regression models were computed to explore the factors associated with IIT. The variables included in the analysis were sex, age group, zone, facility level, regimen line, multi-month dispensing (MMD), and viral load category. Results Of the 573 630 clients analysed in this study, 32% have been recorded as having interrupted treatment. Of the clients investigated, 66% were female (32% had interrupted treatment), 39% were aged 25–34 at their last ART pick-up date (with 32% of them interrupted treatment), 59% received care at secondary level facilities (37% interrupted treatment) and 38% were last receiving between three- to five-month MMD (with 10% of these interrupted treatment). Those less likely to interrupt ART were males (aOR = 0.91), clients on six-month MMD (aOR = 0.01), adults on 2nd line regimen (aOR = 0.09), and paediatrics on salvage regimen (aOR = 0.02). Clients most likely to interrupt ART were located in the South West Zone (aOR = 1.99), received treatment at a tertiary level (aOR = 12.34) or secondary level facilities (aOR = 4.01), and had no viral load (VL) on record (aOR =10.02). Age group was not significantly associated with IIT. Conclusions Sex, zone, facility level, regimen line, MMD, and VL were significantly associated with IIT. MMD of three months and longer (especially six months) had better retention on ART than those on shorter MMD. Not having a VL on record was associated with a considerable risk of IIT.

The corm of Hypoxis hemerocallidea, commonly known as the African potato, is used in traditional medicine to treat several medical conditions such as urinary infections, benign prostate hyperplasia, inflammatory conditions and testicular tumours. The metabolites contributing to the medicinal properties of H. hemerocallidea have been identified in several studies and, more recently, the active terpenoids of the plant were profiled. However, the biosynthetic pathways and the enzymes involved in the production of the terpene metabolites in H. hemerocallidea have not been characterised at a transcriptomic or proteomic level. In this study, total RNA extracted from the corm, leaf and flower tissues of H. hemerocallidea was sequenced on the Illumina HiSeq 2500 platform. A total of 143,549 transcripts were assembled de novo using Trinity and 107,131 transcripts were functionally annotated using the nr, GO, COG, KEGG and SWISS-PROT databases. Additionally, the proteome of the three tissues were sequenced using LC-MS/MS, revealing aspects of secondary metabolism and serving as data validation for the transcriptome. Functional annotation led to the identification of numerous terpene synthases such as nerolidol synthase, germacrene D synthase, and cycloartenol synthase amongst others. Annotations also revealed a transcript encoding the terpene synthase phytoalexin momilactone A synthase. Differential expression analysis using edgeR identified 946 transcripts differentially expressed between the three tissues and revealed that the leaf upregulates linalool synthase compared to the corm and the flower tissues. The transcriptome as well as the proteome of Hypoxis hemerocallidea presented here provide a foundation for future research.

The energetics of ligand binding to human eukaryotic elongation factor 1 gamma (heEF1γ) was investigated using reduced glutathione (GSH), oxidised glutathione (GSSG), glutathione sulfonate and S-hexylglutathione as ligands. The experiments were conducted using isothermal titration calorimetry, and the findings were supported using computational studies. The data show that the binding of these ligands to heEF1γ is enthalpically favourable and entropically driven (except for the binding of GSSG). The full length heEF1γ binds GSSG with lower affinity (K d = 115 μM), with more hydrogen-bond contacts (ΔH = −73.8 kJ/mol) and unfavourable entropy (−TΔS = 51.7 kJ/mol) compared to the glutathione transferase-like N-terminus domain of heEF1γ, which did not show preference to any specific ligand. Computational free binding energy calculations from the 10 ligand poses show that GSSG and GSH consistently bind heEF1γ, and that both ligands bind at the same site with a folded bioactive conformation. This study reveals the possibility that heEF1γ is a glutathione-binding protein.