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The article offers information on the future naming system of African Bemisia tabaci species. Topics discussed include challenges associated with classification and identification within the Bemisia tabaci (Gennadius) species complex; information on plant damage caused by Bemisia tabaci; and determination of Cassava as source of carbohydrate in sub-Saharan Africa. Other topics include adverse impact of sooty mould on photosynthesis and quality of fruit and fibre.

Background: Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of viral replication and immune dysregulation. We aimed to characterise biomarker trajectories and their associations with clinical outcomes., Methods: In this international, prospective cohort study, patients admitted to hospital with COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 platform trial within the Accelerating COVID-19 Therapeutic Interventions and Vaccines programme between Aug 5, 2020 and Sept 30, 2021 were included. Participants were included from 108 sites in Denmark, Greece, Poland, Singapore, Spain, Switzerland, Uganda, the UK, and the USA, and randomised to placebo or one of four neutralising monoclonal antibodies: bamlanivimab (Aug 5 to Oct 13, 2020), sotrovimab (Dec 16, 2020, to March 1, 2021), amubarvimab-romlusevimab (Dec 16, 2020, to March 1, 2021), and tixagevimab-cilgavimab (Feb 10 to Sept 30, 2021). This trial included an analysis of 2149 participants with plasma nucleocapsid antigen, anti-nucleocapsid antibody, C-reactive protein (CRP), IL-6, and D-dimer measured at baseline and day 1, day 3, and day 5 of enrolment. Day-90 follow-up status was available for 1790 participants. Biomarker trajectories were evaluated for associations with baseline characteristics, a 7-day pulmonary ordinal outcome, 90-day mortality, and 90-day rate of sustained recovery., Findings: The study included 2149 participants. Participant median age was 57 years (IQR 46-68), 1246 (58·0%) of 2149 participants were male and 903 (42·0%) were female; 1792 (83·4%) had at least one comorbidity, and 1764 (82·1%) were unvaccinated. Mortality to day 90 was 172 (8·0%) of 2149 and 189 (8·8%) participants had sustained recovery. A pattern of less favourable trajectories of low anti-nucleocapsid antibody, high plasma nucleocapsid antigen, and high inflammatory markers over the first 5 days was observed for high-risk baseline clinical characteristics or factors related to SARS-CoV-2 infection. For example, participants with chronic kidney disease demonstrated plasma nucleocapsid antigen 424% higher (95% CI 319-559), CRP 174% higher (150-202), IL-6 173% higher (144-208), D-dimer 149% higher (134-165), and anti-nucleocapsid antibody 39% lower (60-18) to day 5 than those without chronic kidney disease. Participants in the highest quartile for plasma nucleocapsid antigen, CRP, and IL-6 at baseline and day 5 had worse clinical outcomes, including 90-day all-cause mortality (plasma nucleocapsid antigen hazard ratio (HR) 4·50 (95% CI 3·29-6·15), CRP HR 3·37 (2·30-4·94), and IL-6 HR 5·67 (4·12-7·80). This risk persisted for plasma nucleocapsid antigen and CRP after adjustment for baseline biomarker values and other baseline factors., Interpretation: Patients admitted to hospital with less favourable 5-day biomarker trajectories had worse prognosis, suggesting that persistent viral burden might drive inflammation in the pathogenesis of COVID-19, identifying patients that might benefit from escalation of antiviral or anti-inflammatory treatment., Funding: US National Institutes of Health., Competing Interests: Declaration of interests ALG reports receiving institutional funding from Novavax, institutional partnership with AstraZeneca, and being personally named as inventor on a patent used by AstraZeneca. DDM reports receiving grants from the Danish National Research Foundation. DL reports participation in a study funded by Gilead with no salary support. EM reports payments to his institution received from SciClone Pharmaceuticals, Regeneron Pharmaceuticals, Pfizer, Chemic Labs and KODA Therapeutics, and Cidara, and payment for participating in an advisory board for Basilea. KW reports honorarium for Acute Respiratory Distress Syndrome (ARDS) International Conference in 2023, and travel support from University of California San Francisco. MAM reports institutional funding by the US Department of Defence, Roche-Genetech, and Quantum Health, and personal consulting fees from Gilead, Novartis, and Johnson & Johnson. MKJ reports grants received from Regeneron, Laurent, and Gilead, honoraria from Gilead, and a leadership role with the HIV Medicine Association Board of Directors. PC reports consulting fees from Eli Lilly and Regeneron. All other authors declare no competing interests. All authors were not precluded from accessing data in the study., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Long-acting injectable cabotegravir and rilpivirine is licensed for individualised treatment of HIV-1 infection in resource-rich settings. Additional evidence is required to support use in African treatment programmes where demographic factors, viral subtypes, previous treatment, and delivery and monitoring approaches differ. The aim of this study was to determine whether switching to long-acting therapy with injections every 8 weeks is non-inferior to daily oral therapy in Africa., Methods: CARES is a randomised, open-label, non-inferiority trial being conducted at eight sites in Uganda, Kenya, and South Africa. Participants with HIV viral load below 50 copies per mL on oral antiretroviral therapy and no history of virological failure were randomly assigned (1:1; web-based, permuted blocks) to receive cabotegravir (600 mg) and rilpivirine (900 mg) by intramuscular injection every 8 weeks, or to continue oral therapy. Viral load was monitored every 24 weeks. The primary outcome was week 48 viral load below 50 copies per mL, assessed with the Food and Drug Administration snapshot algorithm (non-inferiority margin 10 percentage points) in the intention-to-treat exposed population. This trial is registered with the Pan African Clinical Trials Registry (202104874490818) and is ongoing up to 96 weeks., Findings: Between Sept 1, 2021, and Aug 31, 2022, we enrolled 512 participants (295 [58%] female; 380 [74%] previous non-nucleoside reverse transcriptase inhibitor exposure). Week 48 viral load was below 50 copies per mL in 246 (96%) of 255 participants in the long-acting therapy group and 250 (97%) of 257 in the oral therapy group (difference -0·8 percentage points; 95% CI -3·7 to 2·3), demonstrating non-inferiority (confirmed in per-protocol analysis). Two participants had virological failure in the long-acting therapy group, both with drug resistance; none had virological failure in the oral therapy group. Adverse events of grade 3 or greater severity occurred in 24 (9%) participants on long-acting therapy and ten (4%) on oral therapy; one participant discontinued long-acting therapy (for injection-site reaction)., Interpretation: Long-acting therapy had non-inferior efficacy compared with oral therapy, with a good safety profile, and can be considered for African treatment programmes., Funding: Janssen., Competing Interests: Declaration of interests CK reports funding paid to institution and donation of drugs to institution from Janssen for the work reported in this manuscript. SS reports funding paid to institution and personal fees for speaking at symposia from Janssen and donation of drugs to institution from ViiV, all outside the work reported in this manuscript. FC reports funding paid to institution and donation of drugs to institution from Janssen and funding paid to institution from ViiV, Gilead, Wellcome Trust, and the National Institute of Health Research UK outside the work reported in this manuscript; and unpaid role as Chair of Steering Committee for an investigator-initiated long-acting implementation trial. KM reports personal fees for speaking at symposia from Janssen outside of the work reported in this manuscript. VVE is an employee of Johnson & Johnson and holds stock options in Johnson & Johnson; and a patent related to rilpivirine. PM was an employee of Janssen at the time of trial design, and then an employee of ViiV during the time of trial conduct, manuscript submission, and publication; and holds stock from GSK as an employee of ViiV. FAB is an employee of Johnson & Johnson and holds stock options of Johnson & Johnson. NIP reports grants paid to institution, donation of drugs to institution, and personal fees for speaking at symposia from Janssen outside the work reported in this manuscript; and is the Chief Investigator on a trial with funding paid to institution by the EU for testing anti-tuberculosis drug combinations based on the drug ganfeborole, owned by GSK. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Critical drug-drug interactions (DDI) and hepatotoxicity complicate concurrent use of rifampicin and protease inhibitors. We investigated whether dose escalation of atazanavir/ritonavir could safely overcome the DDI with rifampicin., Methods: DERIVE (NCT04121195, EDCTP) was a dose-escalation trial in people with human immunodeficiency virus (HIV) on atazanavir/ritonavir-based antiretroviral therapy (ART) in Uganda. Four intensive pharmacokinetic (PK) visits were performed: PK1 300/100 mg OD (baseline); PK2 300/100 mg OD with rifampicin 600 mg; PK3 300/100 mg twice a day (BID) with rifampicin 600 mg OD; PK4 300/100 mg BID with rifampicin 1200 mg OD. Dolutegravir 50 mg BID throughout the study period ensured participants remained protected from subtherapeutic atazanavir concentrations. The data were interpreted with noncompartmental analysis. The target minimum concentration was atazanavir's protein-adjusted IC90 (PA-IC90), 0.014 mg/L., Results: We enrolled 26 participants (23 female) with median (range) age 44 (28-61) years and weight 67 (50-75) kg. Compared with PK1, atazanavir Ctau, and AUC were significantly reduced at PK2 by 96% and 85%, respectively. The escalation to BID dosing (PK3) reduced this difference in Ctau, and AUC24 to 18% lower and 8% higher, respectively. Comparable exposures were maintained with double doses of rifampicin. Lowest Ctau during PK1, PK3, and PK4 were 12.7-, 4.8-, and 8.6-fold higher than PA-IC90, respectively, whereas 65% of PK2 Ctau were below the limit of quantification (0.03 mg/L), hence likely below PA-IC90. No participant developed significant elevation of liver enzymes, reported a serious adverse event (SAE) or experienced rebound viraemia., Conclusions: Twice daily atazanavir/ritonavir during rifampicin co-administration was well tolerated and achieved plasma concentrations above the target., Clinical Trials Registration: NCT04121195. Registered on 09 October 2019, https://clinicaltrials.gov/ct2/show/NCT04121195., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood., Methods: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models., Results: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P < .001), and a steeper rate of decline through the first 5 days (P < .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale., Conclusions: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed., Clinical Trials Registration: NCT04501978., Competing Interests: Potential conflicts of interest. A. L. G. reports receiving institutional funding from Novavax, insititutaional partnership with Astra Zeneca, and reports being personally named as inventor on a patent used by Astra Zeneca. D. D. M. reports receiving grant from the Danish National research Foundation. E. M. reports payments to his institution received from SciClone Pharmaceuticals, Regeneron Pharmaceuticals, Pfizer, Chemic Labs/KODA Therapeutics, Cidara, and Leidos Biomedical Research Inc; E. M. also reports being on an advisory board for Basilea. K. W. reports receiving a honorarium for international ARDS conference and travel support from UCSF. M. A. reports a grant from NINDS. M. A. M. reports institutional grants from NHLBI/NIAID, the department of defence, California Institute of Regeneration, Roche-Genentech, and Quantum Health. M. A. M. has also received personal consulting fees from Novartis, Pliant Therapeutics, Johnson and Johnson, Gilead, and Citius Pharmaceuticals. M. K. J. reports institutional grants from Gilead, Laurent, and Regeneron; personal consulting fees from Gilead; and personal honoraria from Cooper Clinic. S. T. is funded by grants from the Australian Medical Foundation and New South Wales Health. The remaining authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The group of > 40 cryptic whitefly species called Bemisia tabaci sensu lato are amongst the world's worst agricultural pests and plant-virus vectors. Outbreaks of B. tabaci s.l. and the associated plant-virus diseases continue to contribute to global food insecurity and social instability, particularly in sub-Saharan Africa and Asia. Published B. tabaci s.l. genomes have limited use for studying African cassava B. tabaci SSA1 species, due to the high genetic divergences between them. Genomic annotations presented here were performed using the 'Ensembl gene annotation system', to ensure that comparative analyses and conclusions reflect biological differences, as opposed to arising from different methodologies underpinning transcript model identification., Results: We present here six new B. tabaci s.l. genomes from Africa and Asia, and two re-annotated previously published genomes, to provide evolutionary insights into these globally distributed pests. Genome sizes ranged between 616-658 Mb and exhibited some of the highest coverage of transposable elements reported within Arthropoda. Many fewer total protein coding genes (PCG) were recovered compared to the previously published B. tabaci s.l. genomes and structural annotations generated via the uniform methodology strongly supported a repertoire of between 12.8-13.2 × 10 3 PCG. An integrative systematics approach incorporating phylogenomic analysis of nuclear and mitochondrial markers supported a monophyletic Aleyrodidae and the basal positioning of B. tabaci Uganda-1 to the sub-Saharan group of species. Reciprocal cross-mating data and the co-cladogenesis pattern of the primary obligate endosymbiont 'Candidatus Portiera aleyrodidarum' from 11 Bemisia genomes further supported the phylogenetic reconstruction to show that African cassava B. tabaci populations consist of just three biological species. We include comparative analyses of gene families related to detoxification, sugar metabolism, vector competency and evaluate the presence and function of horizontally transferred genes, essential for understanding the evolution and unique biology of constituent B. tabaci. s.l species., Conclusions: These genomic resources have provided new and critical insights into the genetics underlying B. tabaci s.l. biology. They also provide a rich foundation for post-genomic research, including the selection of candidate gene-targets for innovative whitefly and virus-control strategies., (© 2023. The Author(s).)

Background: Shorter treatments are needed for drug-susceptible tuberculosis. Adjunctive statins increase bactericidal activity in preclinical tuberculosis models. We investigated the safety and efficacy of adjunctive rosuvastatin in people with tuberculosis. We tested the hypothesis that adjunctive rosuvastatin accelerates sputum culture conversion within the first 8 weeks of treatment of rifampicin-susceptible tuberculosis., Methods: This phase 2b, randomised, open-label, multicentre trial conducted in five hospitals or clinics in three countries with high tuberculosis burden (ie, the Philippines, Viet Nam, and Uganda) enrolled adult participants aged 18-75 years with sputum smear or Xpert MTB/RIF positive, rifampicin-susceptible tuberculosis who had received less than 7 days of previous tuberculosis treatment. Participants were randomly assigned via a web-based system to receive either 10 mg rosuvastatin once per day for 8 weeks plus standard tuberculosis therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol; rosuvastatin group) or standard tuberculosis therapy alone (control group). Randomisation was stratified by trial site, history of diabetes, and HIV co-infection. Laboratory staff and central investigators involved in data cleaning and analysis were masked to treatment allocation, but study participants and site investigators were not. Both groups continued standard treatment to week 24. Sputum samples were collected once per week for the first 8 weeks after randomisation, and then at weeks 10, 12, and 24. The primary efficacy outcome was time to culture conversion (TTCC; days) in liquid culture by week 8, assessed in randomised participants who had microbiological confirmation of tuberculosis, took at least one dose of rosuvastatin, and who did not show resistance to rifampicin (modified intention-to-treat population), for which groups were compared with the Cox proportional hazards model. The main safety outcome was grade 3-5 adverse events by week 24, assessed in the intention-to-treat population, for which groups were compared with Fisher's exact test. All participants completed 24 weeks of follow-up. This trial is registered with ClinicalTrials.gov (NCT04504851)., Findings: Between Sept 2, 2020, and Jan 14, 2021, 174 participants were screened and 137 were randomly assigned to the rosuvastatin group (70 participants) or control group (67 participants). In the modified intention-to-treat population of 135 participants, 102 (76%) were men and 33 (24%) were women. Median TTCC in liquid media was 42 days (95% CI 35-49) in the rosuvastatin group (68 participants) and 42 days (36-53) in the control group (67 participants; hazard ratio 1·30 [0·88-1·91], p=0·19). Grade 3-5 adverse events occurred in six (9%) of 70 in the rosuvastatin group (none were considered related to rosuvastatin) and four (6%) of 67 in the control group (p=0·75). There were no serious adverse events that were considered to be related to rosuvastatin., Interpretation: Adjunctive rosuvastatin at 10 mg once per day was safe but did not produce substantive benefits on culture conversion in the overall study population. Future trials could explore the safety and efficacy of higher doses of adjunctive rosuvastatin., Funding: National Medical Research Council, Singapore., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The gene and cell therapy field saw its first approved treatments in Europe in 2012 and the United States in 2017 and is projected to be at least a $10B USD industry by 2025. Despite this success, a massive gap exists between the companies, clinics, and researchers developing these therapeutic approaches, and their availability to the patients who need them. The unacceptable reality is a geographic exclusion of low-and middle-income countries (LMIC) in gene therapy development and ultimately the provision of gene therapies to patients in LMIC. This is particularly relevant for gene therapies to treat human immunodeficiency virus infection and hemoglobinopathies, global health crises impacting tens of millions of people primarily located in LMIC. Bridging this divide will require research, clinical and regulatory infrastructural development, capacity-building, training, an approval pathway and community adoption for success and sustainable affordability. In 2020, the Global Gene Therapy Initiative was formed to tackle the barriers to LMIC inclusion in gene therapy development. This working group includes diverse stakeholders from all sectors and has set a goal of introducing two gene therapy Phase I clinical trials in two LMIC, Uganda and India, by 2024. Here we report on progress to date for this initiative., (© 2021. The Author(s).)

Background: Identifying factors that determine the frequency of latently infected CD4+ T cells on antiretroviral therapy (ART) may inform strategies for human immunodeficiency virus (HIV) cure. We investigated the role of CD4+ count at ART initiation for HIV persistence on ART., Methods: Among participants of the Strategic Timing of Antiretroviral Treatment Study, we enrolled people with HIV (PWH) who initiated ART with CD4+ T-cell counts of 500-599, 600-799, or ≥ 800 cells/mm3. After 36-44 months on ART, the levels of total HIV-DNA, cell-associated unspliced HIV-RNA (CA-US HIV-RNA), and two-long terminal repeat HIV-DNA in CD4+ T cells were quantified and plasma HIV-RNA was measured by single-copy assay. We measured T-cell expression of Human Leucocyte Antigen-DR Isotype (HLA-DR), programmed death-1, and phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+ strata., Results: We enrolled 146 PWH, 36 in the 500-599, 60 in the 600-799, and 50 in the ≥ 800 CD4 strata. After 36-44 months of ART, total HIV-DNA, plasma HIV-RNA, and HLA-DR expression were significantly lower in PWH with CD4+ T-cell count ≥ 800 cells/mm3 at ART initiation compared with 600-799 or 500-599 cells/mm3. The median level of HIV-DNA after 36-44 months of ART was lower by 75% in participants initiating ART with ≥ 800 vs 500-599 cells/mm3 (median [interquartile range]: 16.3 [7.0-117.6] vs 68.4 [13.7-213.1] copies/million cells, respectively). Higher pSTAT5 expression significantly correlated with lower levels of HIV-DNA and CA-US HIV-RNA. Virological measures were significantly lower in females., Conclusions: Initiating ART with a CD4+ count ≥ 800 cells/mm3 compared with 600-799 or 500-599 cells/mm3 was associated with achieving a substantially smaller HIV reservoir on ART., Competing Interests: Potential conflicts of interest. T. A. R. has received funding from the Danish Research Council, Region Midt Denmark, The Australian Centre for HIV and Hepatitis Virology Research, Melbourne HIV Cure Consortium, and Gilead outside the submitted work and payment for lectures from Gilead Sciences. T. A. R. also reports a leadership or fiduciary role with the HIV Cure Community Partnership Steering Committee in Australia, the 18th European AIDS Conference Scientific Committee, and the Australasian Society for HIV Medicine (ASHM), Taskforce on Blood-borne Viruses (BBV), Sexual Health and COVID-19. D. P. D. was funded by a grant from the National Cancer Institute (grant number RO1-CA228172). S. P. has received funding from the National Health and Medical Research Council of Australia (NHMRC), National Institutes of Health (NIH), amFAR, the Foundation for AIDS Research, and The Australian Centre for HIV and Hepatitis Virology Research. P. M. declares that her institution received funding from the INSIGHT Network to undertake the START study and received a grant from Alfred Health to conduct sample collection and shipment for the HIV Reservoirs substudy of the START trial. C. C. declares receipt of funding from the NHMRC for an Early Career Fellowship. S. B.-F. declares that her institution received funding from the INSIGHT Network to undertake the START study. K. P. declares that she has received unconditional research grants from ViiV Healthcare and Gilead Sciences. P. P. holds shares in Gilead Sciences and GlaxoSmithKline. S. R. L. has received funding from the Australian NHMRC, the Australian Center for HIV and Hepatitis Virology Research NIH, amfAR (Magnet grant award number 19-02602), Gilead Sciences (clinical research grant), Merck, ViiV, and Leidos outside the submitted work. S. R. L. also reports consulting fees from Abivax, Geovax, ViiV, and Tetralogic, honoraria from Gilead Sciences, Bristol Myers Sqibb, and Merck Sharpe & Dohme, an International PCT patent (PCTAU2017050631), and participation on advisory boards for Abivax, Bionor, ViiV, Calimmune, InniVirVax, Aelix Therapeutics, Immunocore, and the French Agency for Research on AIDS and Viral Hepatitis (ANRS) Emerging Infectious Diseases. E. J. W. received research grants from Gilead Sciences, Merck Sharp & Dohme, and The Australian Centre for HIV and Hepatitis Virology Research for this submitted work. E. J. W. reports receipt of research grants from the Victorian, Tasmanian, and South Australian governments; E. J. W. has received free study drug from Gilead Sciences for the VicPrEP study and her institution has received funding from Gilead Sciences, ViiV Healthcare, Abbott, Merck Sharp & Dohme, Boehringer Ingelheim, and Janssen-Cilag. E. J. W. also reports payment for lectures from Gilead Sciences and the Australasian Society of HIV Medicine and participation on an Advisory Board for Gilead Sciences. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

The protection provided by natural versus hybrid immunity from COVID-19 is unclear. We reflect on the challenges from trying to conduct a randomized post-SARS-CoV-2 infection vaccination trial study with rapidly evolving scientific data, vaccination guidelines, varying international policies, difficulties with vaccine availability, vaccine hesitancy, and a constantly evolving virus., Competing Interests: Declaration of interests D.L.B is on the advisory boards of Gilead, MerckSharpe & Dohme, Pfizer, and ViiV, and receives travel grants from ViiV Healthcare. G.M. receives research grants from Gilead, AbbvieInc., ViiV Healthcare, and Janssen, and is on the advisory boards of Gileadand AstraZeneca. The other authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Begomoviruses are transmitted by several cryptic species of the sweetpotato whitefly, Bemisia tabaci (Gennadius), in a persistent and circulative manner. Upon virus acquisition and circulative translocation within the whitefly, a multitude of molecular interactions occur. This study investigated the differentially expressed transcript profiles associated with the acquisition of the Old World monopartite begomovirus, tomato yellow leaf curl virus (TYLCV), and two New World bipartite begomoviruses, sida golden mosaic virus (SiGMV) and cucurbit leaf crumple virus (CuLCrV), in two invasive B. tabaci cryptic species, Middle East-Asia Minor 1 (MEAM1) and Mediterranean (MED). A total of 881 and 559 genes were differentially expressed in viruliferous MEAM1 and MED whiteflies, respectively, compared with their non-viruliferous counterparts, of which 146 genes were common between the two cryptic species. For both cryptic species, the number of differentially expressed genes (DEGs) associated with TYLCV and SiGMV acquisition were higher compared with DEGs associated with CuLCrV acquisition. Pathway analysis indicated that the acquisition of begomoviruses induced differential changes in pathways associated with metabolism and organismal systems. Contrasting expression patterns of major genes associated with virus infection and immune systems were observed. These genes were generally overexpressed and underexpressed in B. tabaci MEAM1 and MED adults, respectively. Further, no specific expression pattern was observed among genes associated with fitness (egg production, spermatogenesis, and aging) in viruliferous whiteflies. The weighted gene correlation network analysis of viruliferous B. tabaci MEAM1 and MED adults identified different hub genes potentially implicated in the vector competence and circulative tropism of viruses. Taken together, the results indicate that both vector cryptic species and the acquired virus species could differentially affect gene expression.

Background: WHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine., Methods: In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete., Findings: Between July 30 and Dec 18, 2019, we screened 783 patients and enrolled 465. One participant was randomly assigned in error and immediately withdrawn. The remaining 464 participants were randomly assigned to receive either dolutegravir (n=235) or ritonavir-boosted darunavir (n=229) and to receive lamivudine plus either tenofovir (n=233) or zidovudine (n=231). At week 96, 211 (90%) of 235 participants in the dolutegravir group and 199 (87%) of 229 participants in the darunavir group had HIV-1 RNA less than 400 copies per mL (percentage point difference 2·9, 95% CI -3·0 to 8·7), indicating non-inferiority. Nine (4%) participants (all in the dolutegravir group) developed dolutegravir resistance; no participants developed darunavir resistance (p=0·0023). In the other randomised comparison, 214 (92%) of 233 patients in the tenofovir group and 196 (85%) of 231 patients in the zidovudine group had HIV-1 RNA less than 400 copies per mL (percentage point difference 7·0, 95% CI 1·2 to 12·8), showing non-inferiority and indicating the superiority of tenofovir (p=0·019). The proportions of participants with any grade 3-4 adverse event were similar between the dolutegravir (26 [11%]) and darunavir (28 [12%]) groups and between the tenofovir (22 [9%]) and zidovudine (32 [14%]) groups. There were no deaths related to study medication., Interpretation: Dolutegravir-based and darunavir-based regimens maintain good viral suppression during 96 weeks; dolutegravir is non-inferior to darunavir but is at greater risk of resistance in second-line therapy. Tenofovir should be continued in second-line therapy, rather than being switched to zidovudine., Funding: Janssen., Competing Interests: Declaration of interests NIP reports grants paid to his institution and personal fees from Janssen. CK, AL, and HM report grants and the donation of drugs and trial supplies to their institutions from Janssen. AKam reports grants paid to his institution from Janssen. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Cipargamin (KAE609) is a potent antimalarial in a phase II trial. Here we report efficacy, pharmacokinetics, and resistance marker analysis across a range of cipargamin doses. These were secondary endpoints from a study primarily conducted to assess the hepatic safety of cipargamin (hepatic safety data are reported elsewhere)., Methods: This phase II, multicenter, randomized, open-label, dose-escalation trial was conducted in sub-Saharan Africa in adults with uncomplicated Plasmodium falciparum malaria. Cipargamin monotherapy was given as single doses up to 150 mg or up to 50 mg once daily for 3 days, with artemether-lumefantrine as control. Key efficacy endpoints were parasite clearance time (PCT), and polymerase chain reaction (PCR)-corrected and uncorrected adequate clinical and parasitological response (ACPR) at 14 and 28 days. Pharmacokinetics and molecular markers of drug resistance were also assessed., Results: All single or multiple cipargamin doses ≥50 mg were associated with rapid parasite clearance, with median PCT of 8 hours versus 24 hours for artemether-lumefantrine. PCR-corrected ACPR at 14 and 28 days was >75% and 65%, respectively, for each cipargamin dose. A treatment-emerging mutation in the Pfatp4 gene, G358S, was detected in 65% of treatment failures. Pharmacokinetic parameters were consistent with previous data, and approximately dose proportional., Conclusions: Cipargamin, at single doses of 50 to 150 mg, was associated with very rapid parasite clearance, PCR-corrected ACPR at 28 days of >65% in adults with uncomplicated P. falciparum malaria, and recrudescent parasites frequently harbored a treatment-emerging mutation. Cipargamin will be further developed with a suitable combination partner., Clinical Trials Registration: ClinicalTrials.gov (NCT03334747)., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Middle East-Asia Minor 1 (MEAM1) and Mediterranean (MED) are two of the most invasive members of the sweetpotato whitefly, Bemisia tabaci, cryptic species complexes and are efficient vectors of begomoviruses. Bemisia tabaci MEAM1 is the predominant vector of begomoviruses in open-field vegetable crops in the southeastern United States. However, recently B. tabaci MED also has been detected in the landscape outside of greenhouses in Florida and Georgia. This study compared the transmission efficiency of one Old-World (OW) and two New-World (NW) begomoviruses prevalent in the southeastern United States, viz., tomato yellow leaf curl virus (TYLCV), cucurbit leaf crumple virus (CuLCrV), and sida golden mosaic virus (SiGMV) between B. tabaci MEAM1 and B. tabaci MED. Bemisia tabaci MEAM1 efficiently transmitted TYLCV, CuLCrV, or SiGMV, whereas B. tabaci MED only transmitted TYLCV. Percent acquisition and retention of OW TYLCV following a 72 h acquisition access period was significantly higher for B. tabaci MED than B. tabaci MEAM1. In contrast, B. tabaci MEAM1 acquired and retained significantly more NW bipartite begomoviruses, CuLCrV or SiGMV, than B. tabaci MED. Quantitative analysis (qPCR) of virus DNA in whitefly internal tissues revealed reduced accumulation of CuLCrV or SiGMV in B. tabaci MED than in B. tabaci MEAM1. Fluorescent in situ hybridization (FISH) showed localization of CuLCrV or SiGMV in the midgut of B. tabaci MED and B. tabaci MEAM1. However, localization of CuLCrV or SiGMV was only observed in the primary salivary glands of B. tabaci MEAM1 and not B. tabaci MED. TYLCV localization was observed in all internal tissues of B. tabaci MEAM1 and B. tabaci MED. Overall, results demonstrate that both B. tabaci MEAM1 and B. tabaci MED are efficient vectors of OW TYLCV. However, for the NW begomoviruses, CuLCrV and SiGMV, B. tabaci MEAM1 seems to a better vector.

This review provides a synopsis of transcriptional responses pertaining to interactions between plant viruses and the insect vectors that transmit them in diverse modes. In the process, it attempts to catalog differential gene expression pertinent to virus-vector interactions in vectors such as virus reception, virus cell entry, virus tissue tropism, virus multiplication, and vector immune responses. Whiteflies, leafhoppers, planthoppers, and thrips are the main insect groups reviewed, along with aphids and leaf beetles. Much of the focus on gene expression pertinent to vector-virus interactions has centered around whole-body RNA extraction, whereas data on virus-induced tissue-specific gene expression in vectors is limited. This review compares transcriptional responses in different insect groups following the acquisition of non-persistent, semi-persistent, and persistent (non-propagative and propagative) plant viruses and identifies parallels and divergences in gene expression patterns. Understanding virus-induced changes in vectors at a transcriptional level can aid in the identification of candidate genes for targeting with RNAi and/or CRISPR editing in insect vectors for management approaches.

Background: The novel anti-malarial cipargamin (KAE609) has potent, rapid activity against Plasmodium falciparum. Transient asymptomatic liver function test elevations were previously observed in cipargamin-treated subjects in two trials: one in malaria patients in Asia and one in volunteers with experimentally induced malaria. In this study, the hepatic safety of cipargamin given as single doses of 10 to 150 mg and 10 to 50 mg once daily for 3 days was assessed. Efficacy results, frequency of treatment-emerging mutations in the atp4 gene and pharmacokinetics have been published elsewhere. Further, the R561H mutation in the k13 gene, which confers artemisinin-resistance, was associated with delayed parasite clearance following treatment with artemether-lumefantrine in Rwanda in this study. This was also the first study with cipargamin to be conducted in patients in sub-Saharan Africa., Methods: This was a Phase II, multicentre, randomized, open-label, dose-escalation trial in adults with uncomplicated falciparum malaria in five sub-Saharan countries, using artemether-lumefantrine as control. The primary endpoint was ≥ 2 Common Terminology Criteria for Adverse Events (CTCAE) Grade increase from baseline in alanine aminotransferase (ALT) or aspartate transaminase (AST) during the 4-week trial., Results: Overall, 2/135 patients treated with cipargamin had ≥ 2 CTCAE Grade increases from baseline in ALT or AST compared to 2/51 artemether-lumefantrine patients, with no significant difference between any cipargamin treatment group and the control group. Cipargamin exposure was comparable to or higher than those in previous studies. Hepatic adverse events and general safety and tolerability were similar for all cipargamin doses and artemether-lumefantrine. Cipargamin was well tolerated with no safety concerns., Conclusions: This active-controlled, dose escalation study was a detailed assessment of the hepatic safety of cipargamin, across a wide range of doses, in patients with uncomplicated falciparum malaria. Comparison with previous cipargamin trials requires caution as no clear conclusion can be drawn as to whether hepatic safety and potential immunity to malaria would differ with ethnicity, patient age and or geography. Previous concerns regarding hepatic safety may have been confounded by factors including malaria itself, whether natural or experimental infection, and should not limit the further development of cipargamin. Trial registration ClinicalTrials.gov number: NCT03334747 (7 Nov 2017), other study ID CKAE609A2202., (© 2021. The Author(s).)

In sub-Saharan Africa cassava growing areas, two members of the Bemisia tabaci species complex termed sub-Saharan Africa 1 (SSA1) and SSA2 have been reported as the prevalent whiteflies associated with the spread of viruses that cause cassava mosaic disease (CMD) and cassava brown streak disease (CBSD) pandemics. At the peak of CMD pandemic in the late 1990s, SSA2 was the prevalent whitefly, although its numbers have diminished over the last two decades with the resurgence of SSA1 whiteflies. Three SSA1 subgroups (SG1 to SG3) are the predominant whiteflies in East Africa and vary in distribution and biological properties. Mating compatibility between SSA1 subgroups and SSA2 whiteflies was reported as the possible driver for the resurgence of SSA1 whiteflies. In this study, a combination of both phylogenomic methods and reciprocal crossing experiments were applied to determine species status of SSA1 subgroups and SSA2 whitefly populations. Phylogenomic analyses conducted with 26 548 205 bp whole genome single nucleotide polymorphisms (SNPs) and the full mitogenomes clustered SSA1 subgroups together and separate from SSA2 species. Mating incompatibility between SSA1 subgroups and SSA2 further demonstrated their distinctiveness from each other. Phylogenomic analyses conducted with SNPs and mitogenomes also revealed different genetic relationships among SSA1 subgroups. The former clustered SSA1-SG1 and SSA1-SG2 together but separate from SSA1-SG3, while the latter clustered SSA1-SG2 and SSA1-SG3 together but separate from SSA1-SG1. Mating compatibility was observed between SSA1-SG1 and SSA1-SG2, while incompatibility occurred between SSA1-SG1 and SSA1-SG3, and SSA1-SG2 and SSA1-SG3. Mating results among SSA1 subgroups were coherent with phylogenomics results based on SNPs but not the full mitogenomes. Furthermore, this study revealed that the secondary endosymbiont-Wolbachia-did not mediate reproductive success in the crossing assays carried out. Overall, using genome wide SNPs together with reciprocal crossings assays, this study established accurate genetic relationships among cassava-colonizing populations, illustrating that SSA1 and SSA2 are distinct species while at least two species occur within SSA1 species., (© 2020 The Authors. Insect Science published by John Wiley & Sons Australia, Ltd on behalf of Institute of Zoology, Chinese Academy of Sciences.)

Background: The urine lipoarabinomannan (LAM) antigen test is a tuberculosis (TB) diagnostic test with highest sensitivity in individuals with advanced human immunodeficiency virus (HIV). Its role in TB diagnostic algorithms for HIV-positive outpatients remains unclear., Methods: The AIDS Clinical Trials Group (ACTG) A5274 trial demonstrated that empiric TB therapy did not improve 24-week survival compared to isoniazid preventive therapy (IPT) in TB screen-negative HIV-positive adults initiating antiretroviral therapy with CD4 counts <50 cells/µL. Retrospective LAM testing was performed on stored urine obtained at baseline. We determined the proportion of LAM-positive participants and conducted modified intent-to-treat analysis excluding LAM-positive participants to determine the effect on 24-week survival, TB incidence, and time to TB using Kaplan-Meier method., Results: A5274 enrolled 850 participants; 53% were male and the median CD4 count was 18 (interquartile range, 9-32) cells/µL. Of the 850, 566 (67%) had LAM testing (283 per arm); 28 (5%) were positive (21 [7%] and 7 [2%] in the empiric and IPT arms, respectively). Of those LAM-positive, 1 participant in each arm died and 5 of 21 and 0 of 7 in empiric and IPT arms, respectively, developed TB. After excluding these 28 cases, there were 19 and 21 deaths in the empiric and IPT arms, respectively (P = .88). TB incidence remained higher (4.6% vs 2%, P = .04) and time to TB remained faster in the empiric arm (P = .04)., Conclusions: Among outpatients with advanced HIV who screened negative for TB by clinical symptoms, microscopy, and Xpert testing, LAM testing identified an additional 5% of individuals with TB. Positive LAM results did not change mortality or TB incidence., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The World Health Organization recommends dolutegravir with two nucleoside reverse-transcriptase inhibitors (NRTIs) for second-line treatment of human immunodeficiency virus type 1 (HIV-1) infection. Evidence is limited for the efficacy of this regimen when NRTIs are predicted to lack activity because of drug resistance, as well as for the recommended switch of an NRTI from tenofovir to zidovudine., Methods: In a two-by-two factorial, open-label, noninferiority trial, we randomly assigned patients for whom first-line therapy was failing (HIV-1 viral load, ≥1000 copies per milliliter) to receive dolutegravir or ritonavir-boosted darunavir and to receive tenofovir or zidovudine; all patients received lamivudine. The primary outcome was a week 48 viral load of less than 400 copies per milliliter, assessed with the Food and Drug Administration snapshot algorithm (noninferiority margin for the between-group difference in the percentage of patients with the primary outcome, 12 percentage points)., Results: We enrolled 464 patients at seven sub-Saharan African sites. A week 48 viral load of less than 400 copies per milliliter was observed in 90.2% of the patients in the dolutegravir group (212 of 235) and in 91.7% of those in the darunavir group (210 of 229) (difference, -1.5 percentage points; 95% confidence interval [CI], -6.7 to 3.7; P = 0.58; indicating noninferiority of dolutegravir, without superiority) and in 92.3% of the patients in the tenofovir group (215 of 233) and in 89.6% of those in the zidovudine group (207 of 231) (difference, 2.7 percentage points; 95% CI, -2.6 to 7.9; P = 0.32; indicating noninferiority of tenofovir, without superiority). In the subgroup of patients with no NRTIs that were predicted to have activity, a viral load of less than 400 copies per milliliter was observed in more than 90% of the patients in the dolutegravir group and the darunavir group. The incidence of adverse events did not differ substantially between the groups in either factorial comparison., Conclusions: Dolutegravir in combination with NRTIs was effective in treating patients with HIV-1 infection, including those with extensive NRTI resistance in whom no NRTIs were predicted to have activity. Tenofovir was noninferior to zidovudine as second-line therapy. (Funded by Janssen; NADIA ClinicalTrials.gov number, NCT03988452.)., (Copyright © 2021 Massachusetts Medical Society.)

Within the HIV clinical trial field, there are gaps in existing ethical regulations in relation to post-trial care. There is need to develop post-trial care guidelines that are flexible and sensitive to local contexts and to the specific needs of different groups of participants, particularly in low income contexts. Evidence regarding HIV trial closure and post-trial care is required to underpin the development of appropriate policies in this area. This article reports research from Uganda that develops a new model of 'Facilitated Transition' to conceptualize the transition process of HIV positive trial participants from 'research' to 'usual care' health facilities after trial conclusion. This was a qualitative grounded theory study that included 21 adult HIV positive post-trial participants and 22 research staff, undertaken between October 2014 and August 2015. The findings showed that trial closure is a complex process for HIV positive participants which includes three phases: the pre-closure, trial-closure, and post-trial phases. The model highlights a range of different needs of research participants and suggests specific and person-centred interventions that can be delivered at different phases with the aim of improving health outcomes and experiences for trial participants in low income settings during trial closure. Further research needs to be done to verify the model in other contexts and for other conditions., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Failure on second-line antiretroviral therapy (ART) with protease inhibitor (PI) mutations (VF-M) is on the rise. However, there is a paucity of information on the factors associated with this observation in low-income countries. Knowledge of underlying factors is critical if we are to minimize the number of PLHIV switched to costly third-line ART. Our study investigated the factors associated with VF-M., Methods: We conducted a matched case-control analysis of patients' records kept at the Joint Clinical Research Center, starting from January 2008 to May 2018. We matched records of patients who failed the second-line ART with major PI mutations (cases) with records of patients who were virologically suppressed (controls) by a ratio of 1:3. Data analysis was conducted using STATA Version 14. Categorical variables were compared with the outcomes failure on second-line ART with PI mutations using the Chi-square and Fisher's exact tests where appropriate. Conditional logistic regression for paired data was used to assess the association between the outcome and exposure variables, employing the backward model building procedure., Results: Of the 340 reviewed patients' records, 53% were women, and 6.2% had previous tuberculosis treatment. Males (aOR = 2.58, [CI 1.42-4.69]), and patients concurrently on tuberculosis treatment while on second-line ART (aOR = 5.65, [CI 1.76-18.09]) had higher odds of VF-M. ART initiation between 2001 and 2015 had lower odds of VF-M relative to initiation before the year 2001., Conclusion: Males and patients concomitantly on tuberculosis treatment while on second-line ART are at a higher risk of VF-M. HIV/AIDS response programs should give special attention to this group of people if we are to minimize the need for expensive third-line ART. We recommend more extensive, explorative studies to ascertain underlying factors.

In East Africa, the prevalent Bemisia tabaci whiteflies on the food security crop cassava are classified as sub-Saharan Africa (SSA) species. Economically damaging cassava whitefly populations were associated with the SSA2 species in the 1990s, but more recently, it has been to SSA1 species. To investigate whether biological traits (number of first instar nymphs, emerged adults, proportion of females in progeny and development time) of the cassava whitefly species are significant drivers of the observed field abundance, our study determined the development of SSA1 sub-group (SG) 1 (5 populations), SG2 (5 populations), SG3 (1 population) and SSA2 (1 population) on cassava and eggplant under laboratory conditions. SSA1-(SG1-SG2) and SSA2 populations' development traits were similar. Regardless of the host plant, SSA1-SG2 populations had the highest number of first instar nymphs (60.6 ± 3.4) and emerged adults (50.9 ± 3.6), followed by SSA1-SG1 (55.5 ± 3.2 and 44.6 ± 3.3), SSA2 (45.8 ± 5.7 and 32.6 ± 5.1) and the lowest were SSA1-SG3 (34.2 ± 6.1 and 32.0 ± 7.1) populations. SSA1-SG3 population had the shortest egg-adult emergence development time (26.7 days), followed by SSA1-SG1 (29.1 days), SSA1-SG2 (29.6 days) and SSA2 (32.2 days). Regardless of the whitefly population, development time was significantly shorter on eggplant (25.1 ± 0.9 days) than cassava (34.6 ± 1.0 days). These results support that SSA1-(SG1-SG2) and SSA2 B. tabaci can become highly abundant on cassava, with their species classification alone not correlating with observed abundance and prevalence.

Background: While the proportion of HIV-positive children (under 15 years) enrolled on antiretroviral therapy (ART) has increased in recent years, up to 60% of children started on ART do not achieve virological suppression. We set out to determine the factors associated with virological non-suppression among children living with HIV receiving ART at a peri-urban HIV care clinic in Kampala, Uganda., Method: This was a retrospective cohort study conducted at the pediatric HIV/AIDS clinic at the Joint Clinical Research Centre (JCRC) in Kampala, Uganda. Three hundred (300) HIV-positive children (0-14 years) were randomly selected from existing medical records and data on children's socio-demographic and clinical characteristics (age at ART initiation, WHO clinical staging, and ART-induced side effects) were abstracted using a data abstraction form. Virological non-suppression was defined as a viral load ≥1000 copies/Ml of blood after six months of ART initiation. Incident rate ratios (IRRs) were determined as a measure of association between virological non-suppression and child/patient characteristics. The IRRs were obtained via a modified Poisson regression with corresponding 95% confidence intervals (95%CI). All analyses were done using statistical package, Stata version 15., Results: The overall non-suppression rate among HIV-positive children on ART was 23%. Being at WHO clinical stage 4 at ART initiation [adj. IRR 2.74; 95%CI: 1.63, 4.61] and ART-induced side effects [adj. IRR 1.77; 95%CI: 1.06, 2.97] were significantly associated with non-suppression. Older age at ART initiation (age 5-9 years: [adj. IRR 0.42; 95%CI: 0.28, 0.65]; age 10-14 years: [adj. IRR 0.34; 95%CI: 0.18, 0.64] was less likely to be associated with virological non-suppression., Conclusion: Nearly a quarter of HIV-positive children on ART had a non-suppressed viral load after six months of treatment. Being at WHO clinical stage 4 at ART initiation and ART-induced side effects were significantly associated with virological non-suppression while older age at ART initiation was protective. Our findings suggest a need for age-specific interventions, particularly those targeting children below five years of age, to improve virological suppression among HIV-positive children receiving ART in this setting., Competing Interests: The authors declare that they have no competing interests.

Over the past three decades, highly increased whitefly ( Bemisia tabaci ) populations have been observed on the staple food crop cassava in eastern Africa and associated with ensuing viral disease pandemics and food insecurity. Increased whitefly numbers have also been observed in other key agricultural crops and weeds. Factors behind the population surges on different crops and their interrelationships are unclear, although in cassava they have been associated with specific populations within the Bemisia tabaci species complex known to infest cassava crops in Africa. This study carried out an in-depth survey to understand the distribution of B. tabaci populations infesting crops and uncultivated plant hosts in Uganda, a centre of origin for this pest complex. Whitefly samples were collected from 59 identified plant species and 25 unidentified weeds in a countrywide survey. Identities of 870 individual adult whiteflies were determined through mitochondrial cytochrome oxidase 1 sequences (651 bp) in the 3' barcode region used for B. tabaci systematics. Sixteen B. tabaci and five related whitefly putative species were identified based on > 4.0% nucleotide divergence, of which three are proposed as novel B. tabaci putative species and four as novel closely related whitefly species. The most prevalent whiteflies were classified as B. tabaci MED-ASL (30.5% of samples), sub-Saharan Africa 1 (SSA1, 22.7%) and Bemisia Uganda1 (12.1%). These species were also indicated to be the most polyphagous occurring on 33, 40 and 25 identified plant species, respectively. Multiple (≥ 3) whitefly species occurred on specific crops (bean, eggplant, pumpkin and tomato) and weeds ( Sida acuta and Ocimum gratissimum ). These plants may have increased potential to act as reservoirs for mixed infections of whitefly-vectored viruses. Management of whitefly pest populations in eastern Africa will require an integration of approaches that consider their degree of polyphagy and a climate that enables the continuous presence of crop and uncultivated plant hosts., Supplementary Information: The online version contains supplementary material available at 10.1007/s10340-021-01355-6., Competing Interests: Conflicts of interestThe authors declare that they have no conflict of interests., (© The Author(s) 2021.)

Projected climate changes are thought to promote emerging infectious diseases, though to date, evidence linking climate changes and such diseases in plants has not been available. Cassava is perhaps the most important crop in Africa for smallholder farmers. Since the late 1990's there have been reports from East and Central Africa of pandemics of begomoviruses in cassava linked to high abundances of whitefly species within the Bemisia tabaci complex. We used CLIMEX, a process-oriented climatic niche model, to explore if this pandemic was linked to recent historical climatic changes. The climatic niche model was corroborated with independent observed field abundance of B. tabaci in Uganda over a 13-year time-series, and with the probability of occurrence of B. tabaci over 2 years across the African study area. Throughout a 39-year climate time-series spanning the period during which the pandemics emerged, the modelled climatic conditions for B. tabaci improved significantly in the areas where the pandemics had been reported and were constant or decreased elsewhere. This is the first reported case where observed historical climate changes have been attributed to the increase in abundance of an insect pest, contributing to a crop disease pandemic.

Bemisia tabaci is an important vector of cassava brown streak viruses and cassava mosaic begomoviruses, the causal agents of cassava brown streak disease and cassava mosaic disease (CMD), respectively. A study was carried out to determine the genetic variability of B. tabaci associated with cassava and the occurrence of CMD in Zambia in 2013 and 2015. Phylogenetic analysis showed the presence of only the sub-Saharan Africa 1 (SSA1) genetic group in Zambia. The SSA1 population had three population subgroups (SGs): SSA1-SG1, SSA1-SG2 and SSA1-SG3. All three SSA1 population subgroups occurred in Western Province. However, only SSA1-SG3 occurred in Eastern Province, while only SSA1-SG1 occurred in North Western and Luapula Provinces. Adult B. tabaci were most abundant in Western Province in 2013 (11.1/plant) and 2015 (10.8/plant), and least abundant (0.2/plant) in Northern Province in both 2013 and 2015. CMD was prevalent in all seven provinces surveyed, with the highest incidence recorded in Lusaka Province in both 2013 (78%) and 2015 (83.6%), and the lowest in Northern Province in both 2013 (26.6%) and 2015 (29.3%). Although SSA1-SG1 occurred at greater abundances than the other subgroups, there was no direct association demonstrated between whitefly subgroup and incidence of CMD. Establishing which B. tabaci genetic groups and populations are associated with CMD and their distribution in the country is a key factor in guiding the development of CMD control strategies for cassava-dependent households.

Mixed infection of plant viruses is ubiquitous in nature and can affect virus-plant-vector interactions differently than single virus infection. While several studies have examined virus-virus interactions involving mixed virus infection, relatively few have examined effects of mixed virus infection on vector preference and fitness, especially when multiple vectors are involved. This study explored how single and mixed viral infection of a non-persistently transmitted cucumber mosaic virus (CMV) and propagative and persistently-transmitted tomato spotted wilt orthotospovirus (TSWV) in pepper, Capsicum annum L., influenced the preference and fitness of their vectors, the green peach aphid, Myzus persicae (Sulzer), and the tobacco thrips, Frankliniella fusca (Hinds), respectively. In general, mixed infected plants exhibited severe symptoms compared with individually infected plants. An antagonistic interaction between the two viruses was observed when CMV titer was reduced following mixed infection with TSWV in comparison with the single infection. TSWV titer did not differ between single and mixed infection. Myzus persicae settling preference and median developmental were not significantly different between CMV and/or TSWV-infected and non-infected plants. Moreover, M. persicae fecundity did not differ between CMV-infected and non-infected pepper plants. However, M. persicae fecundity was substantially greater on TSWV-infected plants than non-infected plants. Myzus persicae fecundity on mixed-infected plants was significantly lower than on singly-infected and non-infected plants. Frankliniella fusca fecundity was higher on CMV and/or TSWV-infected pepper plants than non-infected pepper plants. Furthermore, F. fusca -induced feeding damage was higher on TSWV-infected than on CMV-infected, mixed-infected, or non-infected pepper plants. Overall, our results indicate that the effects of mixed virus infection on vectors were not different from those observed following single virus infection. Virus-induced host phenotype-modulated effects were realized on both specific and non-specific vectors, suggesting crosstalk involving all vectors and viruses in this pathosystem. The driving forces of these interactions need to be further examined. The effects of interactions between two viruses and two vectors towards epidemics of one or both viruses also need to be examined.

Despite an increasing need for clinical trials involving people living with HIV (PLWH), little is known about how PLWH experience trial closure, particularly in low-income countries, where the majority of trials take place. We sought to explore the impact of trial closure on PLWH in Uganda. This was an interpretive, grounded theory study using in-depth interviews, conducted between October 2014 and August 2015. Adult participants (N = 23) from 3 trials were included. The findings indicated that trial closure was represented as "moving to another world" and was an emotional transition, linked to a loss of quality care in the research environment, the need to find alternative health facilities, fear of experiencing unwanted side effects, a desire to receive trial feedback, and difficulties linking to posttrial care. We concluded that PLWH leaving trials in a resource-limited setting required holistic care to facilitate their transition back to "usual care."

Introduction: Antiretroviral therapy (ART) has changed the course of HIV/AIDs by enabling patients to live longer, raising concern of the co- existence of HIV with other chronic illnesses, notably non-communicable diseases (NCDs). NCDs are on the rise in developing countries and evidence shows higher occurrence among people living with HIV (PLHIV). In Uganda, the burden of NCDs among PLHIV remains largely unquantified., Objective: To determine the prevalence of hypertension, osteoporosis, diabetes mellitus, renal impairment, asthma, cardiomyopathy and multi-morbidity among HIV positive patients, receiving Anti-Retroviral Therapy at Joint Clinical Research Centre, Lubowa, Uganda., Methods: This was a cross-sectional study conducted among 387 systematically sampled patients, receiving ART at the Joint Clinical Research Centre, Lubowa, between March and April 2017. The study used data extracted from routine care patient files to identify individuals with non-communicable diseases. Prevalence of the NCDs was estimated and reported with 95% confidence intervals. Prevalence was also reported at various levels of socio- demographic, behavioural and clinical factors., Results: The overall prevalence of having at least one NCD was 20.7% (95% CI: 16.7-24.5). The prevalence of hypertension was 12.4% (95% CI: 9.1-15.7), osteoporosis 6.5% (95% CI: 4.0-8.9), diabetes mellitus 4.7% (95% CI: 2.6-6.8), renal impairment 1.6% (95% CI: 0.3-2.8), asthma 1.6% (95% CI: 0.3-2.8), and cardiomyopathy 1.3% (95% CI: 0.2-2.4). Prevalence of multi-morbidity was 4.7% (95% CI: 2.6-6.8). Prevalence was significantly higher among older participants, widowed participants and individuals with an opportunistic infection., Conclusion: Non-communicable diseases are common among people living with HIV. There is need to encourage early diagnosis and treatment of non-communicable diseases in PLHIV in Uganda., Competing Interests: The authors have declared that no competing interests exist.

Self-management of HIV is a desirable goal for the millions of adolescent persons living with HIV (PLWH). Adolescent PLWH continue to experience poor HIV care outcomes, primarily due to poor rates of medication adherence and retention in care, highlighting a need to develop adolescent self-management skills. The aim of our study was to examine adolescent, caregiver, and health care provider perceptions of adolescent PLWH self-management roles, barriers, and facilitators. Swendeman et al.'s self-management framework for chronic diseases guided the analyses. Participant narratives highlighted perceptions of their responsibilities and related challenges with regard to self-management of HIV by adolescents. Our findings highlighted the complexity of HIV self-management for adolescents and underscored the need for multifaceted programs to strengthen adolescent-caregiver-health care provider partnerships in order to improve adolescent PLWH health and wellbeing.

Objective: We aimed to investigate potential causes of higher risk of treatment interruptions within the multicountry Strategic Timing of AntiRetroviral Treatment (START) trial in 2015., Methods: We defined baseline as the date of starting antiretroviral therapy (ART) and a treatment interruption as discontinuing ART for at least 2 weeks. Participants were stratified by randomization arm and followed from baseline to earliest end date of the initial phase of START, death, date of consent withdrawn or date of first treatment interruption. Cox regression was used to calculate hazard ratios and 95% confidence intervals for factors that may predict treatment interruptions in each arm., Results: Of the 3438 participants who started ART, 2286 were in the immediate arm and 1152 in the deferred arm. 12.9% of people in the immediate arm and 10.5% of people in the deferred arm experienced at least one treatment interruption by 3 years after starting ART. In adjusted analyses, age [hazard ratio for 35-50 years: 0.75 (95% confidence interval: 0.59-0.97) and >50 years: 0.53 (0.33-0.80) vs. <35 years], education status [hazard ratio for postgraduate education vs. less than high-school education (0.23 (0.10-0.50))] and region [hazard ratio for United States vs. Europe/Israel (3.16 (2.09-4.77))] were significantly associated with treatment interruptions in the immediate arm. In the deferred arm, age and education status were significantly associated with treatment interruptions., Conclusion: Within START, we identified younger age and lower educational attainment as potential causes of ART interruption. There is a need to strengthen adherence advice and wider social support in younger people and those of lower education status.

The heightened vulnerability of adolescents to poor HIV care outcomes underscores the need for interventions that create and promote HIV self-management behavioral skills. Adolescents living with HIV (ALHIV) experience a complex array of physical, emotional, and social challenges that constrain their self-care, but the majority of existing psychosocial programs focus primarily on medication adherence. Understanding adolescents' self-care needs, challenges, and preferences is necessary for developing effective culturally relevant interventions. The involvement of caregivers and stakeholders is also critical to realizing positive self-care outcomes. This article presents the findings from focus group discussions with ALHIV, caregivers, and healthcare providers on self-care. The data were collected as part of formative research in the development of a self-management intervention for Ugandan ALHIV. Participants' discussions on self-care strategies and intervention approaches provide valuable insights to guide the development of interventions to promote positive HIV care outcomes among Ugandan ALHIV.

Self-management of HIV is a desirable goal for the millions of adolescent persons living with HIV (PLWH). Adolescent PLWH continue to experience poor HIV care outcomes, primarily due to poor rates of medication adherence and retention in care, highlighting a need to develop adolescent self-management skills. The aim of our study was to examine adolescent, caregiver, and health care provider perceptions of adolescent PLWH self-management roles, barriers, and facilitators. Swendeman et al.'s self-management framework for chronic diseases guided the analyses. Participant narratives highlighted perceptions of their responsibilities and related challenges with regard to self-management of HIV by adolescents. Our findings highlighted the complexity of HIV self-management for adolescents and underscored the need for multifaceted programs to strengthen adolescent-caregiver-health care provider partnerships in order to improve adolescent PLWH health and wellbeing.

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability globally. Both cigarette smoking and HIV have been identified as independent risk factors for COPD. We used data from the strategic timing of antiretroviral treatment (START) Pulmonary Substudy to quantify the impact of smoking on rate of lung function decline in HIV., Methods: We included START Pulmonary Substudy participants who contributed at least 2 good quality spirometry measures during the study. Slope of forced expiratory volume in 1 second (FEV1) was estimated using a repeated-measures model adjusted for the treatment group (immediate vs deferred treatment arm of START), age, sex, race, baseline COPD, and region., Results: Of 1026 START Pulmonary Substudy participants, 915 (89%) were included in this analysis. Median follow-up time was 3.9 years. Smokers and nonsmokers were similar in baseline age (median 36 years), but smokers were more likely to be white, male, and from Europe/Israel/Australia. Smokers had faster average FEV1 decline compared with nonsmokers [-38.3 mL/yr vs -25.1 mL/yr; difference of -13.2 mL/yr (95% confidence interval: -23.6 to -2.7); P = 0.013], were more likely to meet criteria for rapid FEV1 decline [7.2%-11.7% more likely (P = 0.09-P = 0.002), depending on the definition of rapid decline], and had borderline, but not statistically significant, higher incident COPD during follow-up (9.7% vs 5.8%, P = 0.06)., Conclusions: Compared to nonsmokers, HIV-positive smokers experience faster decline in lung function. These results underscore the need for a better understanding of how to best support smoking cessation among HIV-positive populations.

Insect-plant associations and their role in diversification are mostly studied in specialists. Here, we aimed to identify macroevolution patterns in the relationships between generalists and their host plants that have the potential to promote diversification. We focused on the Bemisia tabaci species complex containing more than 35 cryptic species. Mechanisms for explaining this impressive diversification have focused so far on allopatric forces that assume a common, broad, host range. We conducted a literature survey which indicated that species in the complex differ in their host range, with only few showing a truly broad one. We then selected six species, representing different phylogenetic groups and documented host ranges. We tested whether differences in the species expression profiles of detoxification genes are shaped more by their phylogenetic relationships or by their ability to successfully utilize multiple hosts, including novel ones. Performance assays divided the six species into two groups of three, one showing higher performance on various hosts than the other (the lower performance group). The same grouping pattern appeared when the species were clustered according to their expression profiles. Only species placed in the lower performance group showed a tendency to lower the expression of multiple genes. Taken together, these findings bring evidence for the existence of a common detoxification "machinery," shared between species that can perform well on multiple hosts. We raise the possibility that this "machinery" might have played a passive role in the diversification of the complex, by allowing successful migration to new/novel environments, leading, in some cases, to fragmentation and speciation., (© 2018 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.)

Bemisia tabaci whitefly species are some of the world's most devastating agricultural pests and plant-virus disease vectors. Elucidation of the phylogenetic relationships in the group is the basis for understanding their evolution, biogeography, gene-functions and development of novel control technologies. We report here the discovery of five new Sub-Saharan Africa (SSA) B. tabaci putative species, using the partial mitochondrial cytochrome oxidase 1 gene: SSA9, SSA10, SSA11, SSA12 and SSA13. Two of them, SSA10 and SSA11 clustered with the New World species and shared 84.8‒86.5% sequence identities. SSA10 and SSA11 provide new evidence for a close evolutionary link between the Old and New World species. Re-analysis of the evolutionary history of B. tabaci species group indicates that the new African species (SSA10 and SSA11) diverged from the New World clade c. 25 million years ago. The new putative species enable us to: (i) re-evaluate current models of B. tabaci evolution, (ii) recognise increased diversity within this cryptic species group and (iii) re-estimate divergence dates in evolutionary time.

Background: Reliability and validity studies of different lumbar curvature analysis and measurement techniques have been documented however there is limited literature on the reliability and validity of subjective visual analysis. Radiological assessment of lumbar lordotic curve aids in early diagnosis of conditions even before neurologic changes set in., Objective: To ascertain the level of reliability and validity of subjective assessment of lumbar lordosis in conventional radiography., Design: A blinded, repeated-measures diagnostic test was carried out on lumbar spine x-ray radiographs., Setting: Radiology Department at Joint Clinical Research Centre (JCRC), Mengo-Kampala-Uganda., Subjects: Seventy (70) lateral lumbar x-ray films were used for this study and were obtained from the archive of JCRC radiology department at Butikiro house, Mengo-Kampala., Results: Poor observer agreement, both inter- and intra-observer, with kappa values of 0.16 was found. Inter-observer agreement was poorer than intra-observer agreement. Kappa values significantly rose when the lumbar lordosis was clustered into four categories without grading each abnormality., Conclusion: The results confirm that subjective assessment of lumbar lordosis has low reliability and validity. Film quality has limited influence on the observer reliability. This study further shows that fewer scale categories of lordosis abnormalities produce better observer reliability.

Background: Uganda's Ministry of Health registered a 12% increase in new Tuberculosis (TB) cases between 2001 and 2005. Of these, 20% were from Kampala district and most from Mulago national referral hospital where the largest and the oldest medical school is found. Medical students are likely to have an increased exposure to TB infection due to their training in hospitals compared to other university students. The study compared the prevalence of TB infection and associated factors among undergraduate medical and veterinary students in Makerere University, Uganda., Methods: This was a cross-sectional study with 232 medical and 250 veterinary undergraduate students. Socio-demographic and past medical history data was collected using questionnaires. A tuberculin skin test was performed on the volar aspect of the left forearm. An induration ≥10 mm in diameter after 48-72 hrs was considered positive. Logistic regression was used to determine association of independent variables with TB infection., Results: The prevalence of TB infection was higher in medical students (44.8%, 95% C.I= 38.4-51.3%) compared to veterinary students (35.2%, 95% C.I = 29.3-41.1%). The significant predictors of TB infection were: being a medical student (aOR=1.56, 95% CI = 1.05-2.31), male sex (aOR=1.75, 95% CI = 1.17-2.63), history of contact with a confirmed TB case (aOR=1.57, 95% CI = 1.06-2.31) and residing at home (aOR=2.08, 95% CI = 1.20-3.61). Among the medical students, having gone to a day compared to boarding high school (aOR=2.31, 95% CI = 1.06-5.04), involvement in extracurricular clinical exposure (aOR=3.39 95% CI = 1.60-7.16), male sex, residence at home, and history of contact with a TB case predicted TB infection., Conclusion: Medical students have a higher prevalence of TB infection than veterinary students probably due to increased exposure during training. There is a need to emphasize TB infection control measures in hospitals and the general community.

From 2006 to 2011, a cohort study was conducted among 1000 children resident in urban and rural settings of Uganda to ascertain and compare the response to antiretroviral therapy (ART) among urban versus rural children and the factors associated with this response. Clinical, immunological, and virological parameters were ascertained at baseline and weeks 24, 48, 96, and 144 after ART initiation. Adherence to ART was assessed at enrollment by self-report (SR) and pill counts (PC). Overall, 499/948 (52.6%) children were resident in rural areas, 504/948 (53.1%) were male, and their mean age was 11.9±4.4 years (urban children) and 11.4±4.1 years (rural children). The urban children were more likely to switch to second-line ART at a rate of 39.9 per 1000 person-years (95% CI: 28.2-56.4) versus 14.9 per 1000 person-years (95% CI: 8.7-25.7), p=0.0038, develop any new WHO 3/4 events at 127/414 (30.7%) versus 108/466 (23.2%), p=0.012, and have a higher cumulative incidence of hospitalization of 54/449 (12.0%) versus 32/499 (6.4%), p=0.003, when compared to rural children. No differences were observed in mean changes in weight, height, CD4 count and percentage, and hemoglobin and viral load between urban and rural children. Adherence of ≥95% was observed in 88.2% of urban versus 91.3% of rural children by SR (p=0.130), and in 78.8% of urban versus 88.8% of rural children by PC (p<0.0001). In this study rural children had more favorable clinical outcomes and were more likely to adhere optimally to ART than urban children.

The genetic variability of whitefly (Bemisia tabaci) species, the vectors of cassava mosaic begomoviruses (CMBs) in cassava growing areas of Kenya, Tanzania, and Uganda, was investigated through comparison of partial sequences of the mitochondria cytochrome oxidase I (mtCOI) DNA in 2010/11. Two distinct species were obtained including sub-Saharan Africa 1 (SSA1), comprising of two sub-clades (I and II), and a South West Indian Ocean Islands (SWIO) species. Among the SSA1, sub-clade I sequences shared a similarity of 97.8-99.7% with the published Uganda 1 genotypes, and diverged by 0.3-2.2%. A pairwise comparison of SSA1 sub-clade II sequences revealed a similarity of 97.2-99.5% with reference southern Africa genotypes, and diverged by 0.5-2.8%. The SSA1 sub-clade I whiteflies were widely distributed in East Africa (EA). In comparison, the SSA1 sub-clade II whiteflies were detected for the first time in the EA region, and occurred predominantly in the coast regions of Kenya, southern and coast Tanzania. They occurred in low abundance in the Lake Victoria Basin of Tanzania and were widespread in all four regions in Uganda. The SWIO species had a sequence similarity of 97.2-97.7% with the published Reunion sequence and diverged by 2.3-2.8%. The SWIO whiteflies occurred in coast Kenya only. The sub-Saharan Africa 2 whitefly species (Ug2) that was associated with the severe CMD pandemic in Uganda was not detected in our study.