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Drug resistance remains a global challenge in children and adolescents living with HIV (CALWH). Characterizing resistance evolution, specifically using next generation sequencing (NGS) can potentially inform care, but remains understudied, particularly in antiretroviral therapy (ART)-experienced CALWH in resource-limited settings. We conducted reverse-transcriptase NGS and investigated short-and long-term resistance evolution and its predicted impact in a well-characterized cohort of Kenyan CALWH failing 1st-line ART and followed for up to ~8 years. Drug resistance mutation (DRM) evolution types were determined by NGS frequency changes over time, defined as evolving (up-trending and crossing the 20% NGS threshold), reverting (down-trending and crossing the 20% threshold) or other. Exploratory analyses assessed potential impacts of minority resistance variants on evolution. Evolution was detected in 93% of 42 participants, including 91% of 22 with short-term follow-up, 100% of 7 with long-term follow-up without regimen change, and 95% of 19 with long-term follow-up with regimen change. Evolving DRMs were identified in 60% and minority resistance variants evolved in 17%, with exploratory analysis suggesting greater rate of evolution of minority resistance variants under drug selection pressure and higher predicted drug resistance scores in the presence of minority DRMs. Despite high-level pre-existing resistance, NGS-based longitudinal follow-up of this small but unique cohort of Kenyan CALWH demonstrated continued DRM evolution, at times including low-level DRMs detected only by NGS, with predicted impact on care. NGS can inform better understanding of DRM evolution and dynamics and possibly improve care. The clinical significance of these findings should be further evaluated. [ABSTRACT FROM AUTHOR]

The objective of this study was to elucidate factors that predicted the initiation of HIV postexposure prophylaxis (PEP) for blood or body fluid exposures evaluated at Rhode Island emergency departments (EDs). The study involved a retrospective review of patient visits to all civilian Rhode Island EDs for these exposures from 1995 to mid-2001. Multivariate logistic regression models were created to evaluate predictors of the offering and the acceptance and receipt of HIV PEP from 1996 to 2001. The search identified 3622 patients who sustained a blood or body fluid exposure. Of these, 43.8% were health care workers (HCWs) and 57.2% were not HCWs. Most (52.0%) of the exposures were nonsexual. HIV PEP was offered to 21.0% and accepted and received by 9.4% of all patients. HIV PEP was offered more often after significant exposures, exposures to known HIV-infected sources, when time elapsed after the exposure was shorter, if the patients were HCWs, adults, presented to a teaching hospital, presented during the latter years of the study, or sustained nonsexual exposures. Once offered HIV PEP, patients who were male, adult, sustained a significant exposure, knew the source was HIV infected, sustained a nonsexual exposure, or were HCWs had a greater odds of accepting and receiving HIV PEP. Even when controlling for exposure significance, HIV status, and time elapsed since the exposure, several factors such as gender and type of hospital that are unrelated to the exposure appeared to influence the initiation of HIV PEP. ED providers should ensure that these factors do not inappropriately restrict its initiation.

Co-infections with sexually transmittable pathogens are common and more likely in women with disturbed vaginal bacteriome. Among those pathogens, the protozoan parasite Trichomonas vaginalis (TV) is most common after accounting for the highly persistent DNA viruses human papillomavirus (HPV) and genital herpes. The parasitic infection often concurs with the dysbiotic syndrome diagnosed as bacterial vaginosis (BV) and both are associated with risks of superimposed viral infections. Yet, the mechanisms of microbial synergisms in evading host immunity remain elusive. We present clinical and experimental evidence for a new role of galectins, glycan-sensing family of proteins, in mixed infections. We assessed participants of the HIV Epidemiology Research Study (HERS) at each of their incident TV visits (223 case visits) matched to controls who remained TV-negative throughout the study. Matching criteria included age, race, BV (by Nugent score), HIV status, hysterectomy, and contraceptive use. Non-matched variables included BV status at 6 months before the matched visit, and variables examined at baseline, within 6 months of and/or at the matched visit e.g. HSV-2, HPV, and relevant laboratory and socio-demographic parameters. Conditional logistic regression models using generalized estimating equations calculated odds ratios (OR) for incident TV occurrence with each log10 unit higher cervicovaginal concentration of galectins and cytokines. Incident TV was associated with higher levels of galectin-1, galectin-9, IL-1β and chemokines (ORs 1.53 to 2.91, p <0.001). Galectin-9, IL-1β and chemokines were up and galectin-3 down in TV cases with BV or intermediate Nugent versus normal Nugent scores (p <0.001). Galectin-9, IL-1β and chemokines were up in TV-HIV and down in TV-HPV co-infections. In-vitro , TV synergized with its endosymbiont Trichomonasvirus (TVV) and BV bacteria to upregulate galectin-1, galectin-9, and inflammatory cytokines. The BV-bacterium Prevotella bivia alone and together with TV downregulated galectin-3 and synergistically upregulated galectin-1, galectin-9 and IL-1β, mirroring the clinical findings of mixed TV–BV infections. P. bivia also downregulated TVV+TV-induced anti-viral response e.g. IP-10 and RANTES, providing a mechanism for conducing viral persistence in TV-BV co-infections. Collectively, the experimental and clinical data suggest that galectin-mediated immunity may be dysregulated and exploited by viral–protozoan–bacterial synergisms exacerbating inflammatory complications from dysbiosis and sexually transmitted infections. [ABSTRACT FROM AUTHOR]

We evaluated treatment failure misclassification in human immunodeficiency virus-infected Kenyan children whose targeted viral loads were determined after suspected immunologic/clinical failure according to 2006 and 2010/2013 World Health Organization guidelines. The misclassification rate was 21% for the 2006 guidelines and 46% for the 2010/2013 guidelines, which supports current recommendations for routine viral load monitoring but not necessarily the proposed CD4 thresholds. [ABSTRACT FROM AUTHOR]

Background Hypertension is the leading global risk factor for mortality. Hypertension treatment and control rates are low worldwide, and delays in seeking care are associated with increased mortality. Thus, a critical component of hypertension management is to optimize linkage and retention to care. Methods/Design This study investigates whether community health workers, equipped with a tailored behavioral communication strategy and smartphone technology, can increase linkage and retention of hypertensive individuals to a hypertension care program and significantly reduce blood pressure among them. The study will be conducted in the Kosirai and Turbo Divisions of western Kenya. An initial phase of qualitative inquiry will assess facilitators and barriers of linkage and retention to care using a modified Health Belief Model as a conceptual framework. Subsequently, we will conduct a cluster randomized controlled trial with three arms: 1) usual care (community health workers with the standard level of hypertension care training); 2) community health workers with an additional tailored behavioral communication strategy; and 3) community health workers with a tailored behavioral communication strategy who are also equipped with smartphone technology. The co-primary outcome measures are: 1) linkage to hypertension care, and 2) one-year change in systolic blood pressure among hypertensive individuals. Cost-effectiveness analysis will be conducted in terms of costs per unit decrease in blood pressure and costs per disability-adjusted life year gained. Discussion This study will provide evidence regarding the effectiveness and cost-effectiveness of strategies to optimize linkage and retention to hypertension care that can be applicable to non-communicable disease management in low- and middle-income countries. Trial registration This trial is registered with www.clinicaltrials.gov (NCT01844596) on 30 April 2013. [ABSTRACT FROM AUTHOR]

Objective: To longitudinally assess the association between plasma viral load (PVL) and genital tract human immunodeficiency virus (GT HIV) RNA among HIV-1 infected women changing highly active antiretroviral therapy (HAART) because of detectable PVL on current treatment. Methods: Women were eligible for the study if they had detectable PVL (defined as two consecutive samples with PVL>1000 copies/mL) and intended to change their current HAART regimen at the time of enrollment. Paired plasma and GT HIV-1 RNA were measured prospectively over 3 years. Longitudinal analyses examined rates of GT HIV-1 RNA shedding and the association with PVL. Results: Sixteen women were followed for a median of 11 visits contributing a total of 205 study visits. At study enrollment, all had detectable PVL and 69% had detectable GT HIV-1 RNA. Half of the women changed to a new HAART regimen with ≥3 active antiretroviral drugs. The probability of having detectable PVL ≥30 days after changing HAART was 0.56 (95% CI: 0.37 to 0.74). Fourteen women (88%) had detectable PVL on a follow-up visit ≥30 or 60 days after changing HAART; and 12 women (75%) had detectable GT HIV-1 RNA on a follow-up visit ≥30 or 60 days after changing HAART. When PVL was undetectable, GT shedding occurred at 11% of visits, and when PVL was detectable, GT shedding occurred at 47% of visits. Conclusions: Some treatment-experienced HIV-infected women continue to have detectable virus in both the plasma and GT following a change in HAART, highlighting the difficulty of viral suppression in this patient population. [ABSTRACT FROM AUTHOR]

Access to antiretroviral therapy is increasing globally and drug resistance evolution is anticipated. Currently, protease (PR) and reverse transcriptase (RT) sequence generation is increasing, including the use of in-house sequencing assays, and quality assessment prior to sequence analysis is essential. We created a computational HIV PR/RT Sequence Quality Analysis Tool (SQUAT) that runs in the R statistical environment. Sequence quality thresholds are calculated from a large dataset (46,802 PR and 44,432 RT sequences) from the published literature (http://hivdb.Stanford.edu). Nucleic acid sequences are read into SQUAT, identified, aligned, and translated. Nucleic acid sequences are flagged if with > five 1-2-base insertions; > one 3-base insertion; > one deletion; >six PR or >18 RT ambiguous bases; > three consecutive PR or >four RT nucleic acid mutations; > zero stop codons; > three PR or > six RT ambiguous amino acids; > three consecutive PR or > four RT amino acid mutations; >zero unique amino acids; or <0.5% or >15% genetic distance from another submitted se-quence. Thresholds are user modifiable. SQUAT output includes a summary report with detailed comments for troubleshooting of flagged sequences, histograms of pairwise genetic distances, neighbor joining phylogenetic trees, and aligned nucleic and amino acid sequences. SQUAT is a stand-alone, free, web-independent tool to ensure use of high-quality HIV PR/RT sequences in interpretation and reporting of drug resistance, while increasing awareness and expertise and facilitating troubleshooting of potentially problematic sequences. [ABSTRACT FROM AUTHOR]

Objectives: To determine how often sexually assaulted adult female emergency department (ED) patients are being offered testing and prophylaxis for sexually transmitted diseases (STDs) and pregnancy and identify factors associated with the offering of tests and prophylaxis. Methods: This is a retrospective study of ED visits for adult female sexual assault in all Rhode Island EDs from January 1995 through June 2001. The percentage of patients offered testing and prophylaxis was calculated. Multivariable logistic regression was used to identify factors related to testing and prophylaxis use for women sustaining an anal/vaginal assault. Results: Of the 780 patients, 78.2% sustained anal/vaginal penetration, 5.0% genital touching only, and 3.7% oral sex only, and 13.1% did not know what happened to them. Of those women anal/vaginally assaulted, 83.8% were offered chlamydia/gonorrhea testing, 69.4% syphilis testing, 82.9% pregnancy testing, 77.0% chlamydia/gonorrhea prophylaxis, 47.6% emergency contraception, and 19.2% HIV prophylaxis. In multivariable logistic regression models, patients evaluated at the state's women's hospital instead of academic or community hospitals and those who sustained anal/vaginal assault instead of other assaults had a greater odds of being offered testing and prophylaxis. In some cases, older women were offered testing and prophylaxis less often than younger women. Conclusions: Testing and prophylaxis for chlamydia/gonorrhea were used much more often than prophylaxis for emergency contraception and HIV, even for patients who were anal/vaginally assaulted. Disparities in testing and prophylaxis exist by type of hospital and, in some cases, by age. Educational campaigns should be instituted to ensure that all women receive adequate testing and prophylaxis commensurate with the exposure they sustained from a sexual assault. [ABSTRACT FROM AUTHOR]

This study quantifies the combined effects of density and environmental factors on young-of-the-year (YOY) winter flounder (Pseudopleuronectes americanus) in Narragansett Bay, Rhode Island. We used a length-based model to estimate growth and mortality rates from June to October each year from 1988 to 1998. In this model, mortality and growth rates are decreasing functions of length and there is variability in individual growth. Maximum-likelihood methods were used to fit the model to length-frequency data collected by the Rhode Island Division of Fish and Wildlife beach-seine survey in Narragansett Bay during the study years. The monthly mortality rate was density dependent and was positively related to temperature. Growth rate was negatively related to density. There was a significant decline in YOY winter flounder abundance during the period of study. The most recent year of the study, 1998, had the lowest density, lowest mortality, low summer temperature, and high growth rate. Thus, growth and mortality during the juvenile stage do not appear to be limiting the recovery of this depleted winter flounder population.Notre étude vise à quantifier les effets combinés de la densité et des facteurs du milieu sur les jeunes Plies rouges (Pseudopleuronectes americanus) de l'année (YOY) de la baie de Narragansett au Rhode Island. Un modèle basé sur les longueurs nous a permis d'estimer les taux de croissance et de mortalité de juin à octobre, chaque année de 1988 à 1998. Dans ce modèle, les taux de mortalité et de croissance sont des fonctions inverses de la longueur et il y a de la variabilité dans la croissance individuelle. Les méthodes de vraisemblance maximale ont servi à ajuster le modèle aux données de longueur/fréquence récoltées lors d'inventaires à la seine de plage par le Rhode Island Division of Fish and Wildlife dans la baie de Narragansett durant les années d'étude. Le taux mensuel de mortalité était relié à la densité et en corrélation positive avec la température. Le taux de croissance affichait une corrélation négative avec la densité. Il y a eu un déclin significatif de l'abondance des jeunes de l'année pendant la période d'étude. Dans la dernière année de l'étude, 1998, la densité et la mortalité étaient à leur niveau le plus bas, la température estivale était basse et le taux de croissance était élevé. Ainsi, la croissance et la mortalité durant la phase juvénile ne semblent pas être les facteurs limitants de la récupération de cette population décimée de Plies rouges.[Traduit par la Rédaction] [ABSTRACT FROM AUTHOR]

Background: Elevated blood pressure (BP) is the leading global risk factor for mortality. Delay in seeking hypertension care is associated with increased mortality.Objectives: This study investigated whether community health workers, equipped with behavioral communication strategies and smartphone technology, can increase linkage of individuals with elevated BP to a hypertension care program in western Kenya and significantly reduce BP.Methods: The study was a cluster randomized trial with 3 arms: 1) usual care (standard training); 2) "paper-based" (tailored behavioral communication, using paper-based tools); and 3) "smartphone" (tailored behavioral communication, using smartphone technology). The co-primary outcomes were: 1) linkage to care; and 2) change in systolic BP (SBP). A covariate-adjusted mixed-effects model was used, adjusting for differential time to follow-up. Bootstrap and multiple imputation were used to handle missing data.Results: A total of 1,460 individuals (58% women) were enrolled (491 usual care, 500 paper-based, 469 smartphone). Average baseline SBP was 159.4 mm Hg. Follow-up measures of linkage were available for 1,128 (77%) and BP for 1,106 (76%). Linkage to care was 49% overall, with significantly greater linkage in the usual care and smartphone arms of the trial. Average overall follow-up SBP was 149.9 mm Hg. Participants in the smartphone arm experienced a modestly greater reduction in SBP versus usual care (-13.1 mm Hg vs. -9.7 mm Hg), but this difference was not statistically significant. Mediation analysis revealed that linkage to care contributed to SBP change.Conclusions: A strategy combining tailored behavioral communication and mobile health (mHealth) for community health workers led to improved linkage to care, but not statistically significant improvement in SBP reduction. Further innovations to improve hypertension control are needed. (Optimizing Linkage and Retention to Hypertension Care in Rural Kenya [LARK]; NCT01844596). [ABSTRACT FROM AUTHOR]

Background: Incorporating social determinants of health into care delivery for chronic diseases is a priority.Objectives: The goal of this study was to evaluate the impact of group medical visits and/or microfinance on blood pressure reduction.Methods: The authors conducted a cluster randomized trial with 4 arms and 24 clusters: 1) usual care (UC); 2) usual care plus microfinance (MF); 3) group medical visits (GMVs); and 4) GMV integrated into MF (GMV-MF). The primary outcome was 1-year change in systolic blood pressure (SBP). Mixed-effects intention-to-treat models were used to evaluate the outcomes.Results: A total of 2,890 individuals (69.9% women) were enrolled (708 UC, 709 MF, 740 GMV, and 733 GMV-MF). Average baseline SBP was 157.5 mm Hg. Mean SBP declined -11.4, -14.8, -14.7, and -16.4 mm Hg in UC, MF, GMV, and GMV-MF, respectively. Adjusted estimates and multiplicity-adjusted 98.3% confidence intervals showed that, relative to UC, SBP reduction was 3.9 mm Hg (-8.5 to 0.7), 3.3 mm Hg (-7.8 to 1.2), and 2.3 mm Hg (-7.0 to 2.4) greater in GMV-MF, GMV, and MF, respectively. GMV and GMV-MF tended to benefit women, and MF and GMV-MF tended to benefit poorer individuals. Active participation in GMV-MF was associated with greater benefit.Conclusions: A strategy combining GMV and MF for individuals with diabetes or hypertension in Kenya led to clinically meaningful SBP reductions associated with cardiovascular benefit. Although the significance threshold was not met in pairwise comparison hypothesis testing, confidence intervals for GMV-MF were consistent with impacts ranging from substantive benefit to neutral effect relative to UC. Incorporating social determinants of health into care delivery for chronic diseases has potential to improve outcomes. (Bridging Income Generation With Group Integrated Care [BIGPIC]; NCT02501746). [ABSTRACT FROM AUTHOR]

HIV-1 drug resistance remains a global challenge, yet access to testing is limited, particularly in resource-limited settings. We examined feasibility and limitations of genotyping using dried filter analytes in treatment-experienced Kenyan youth with HIV. Youth infected with HIV perinatally were enrolled in 2016-2018 at the Academic Model Providing Access to Healthcare in Eldoret, western Kenya. Samples were shipped in real-time at ambient temperature to the US, and those with viral load (VL)>1,000 copies/mL were tested based on convenience. Dried blood spots genotyping was attempted when unsuccessful from Hemaspots. Multiple logistic regression was used to examine predictors of genotyping success. Samples from 49 participants (median age 15 years, 43% female, median CD4 496 cells/μL [18%], median 8 years on therapy, median VL 11,827 copies/mL) were shipped after median 7 days from collection, arrived in 20 shipments after median 5 days, and extracted after median 2 days (1 day for samples processed on arrival; and 42 days for frozen Hemaspots). Overall, 29/49 (59%) samples with VL > 1,000 copies/mL and 25/32 (78%) with VL > 5,000 copies/mL were genotyped by either Hemaspots or DBS. Successful genotyping was associated with higher Hemaspot volume and higher VL. Real-life HIV-1 drug resistance testing from dried filter analytes is feasible, even in settings with constrained resources. Findings, particularly relevant where resistance testing is limited for clinical care, raise awareness to implementation practicability of this guidelines-recommended test in care of more individuals and populations. Further optimization of filter analytes is needed to overcome related challenges. IMPORTANCE In this manuscript we use dried filter analytes shipped from Kenya to the US in real time, to demonstrate the real-life feasibility of conducting HIV drug resistance testing in a vulnerable population of young children and adolescents with HIV in a resource limited setting. Such testing, which is recommended in resource-rich settings, is unavailable in most resource limited settings for individual clinical care. We show that real-life HIV drug resistance testing from dried filter analytes is feasible, even in settings with constrained resources. These findings raise awareness to the importance of HIV drug resistance for individual care, even in such settings, and emphasize the implementation practicability of this guidelines-recommended test.

Objectives: Management of cardiovascular disease (CVD) is an urgent challenge in low-income and middle-income countries, and interventions may require appraisal of patients' social networks to guide implementation. The purpose of this study is to determine whether egocentric social network characteristics (SNCs) of patients with chronic disease in western Kenya are associated with overall CVD risk and individual CVD risk factors., Design: Cross-sectional analysis of enrollment data (2017-2018) from the Bridging Income Generation with GrouP Integrated Care trial. Non-overlapping trust-only, health advice-only and multiplex (trust and health advice) egocentric social networks were elicited for each participant, and SNCs representing social cohesion were calculated., Setting: 24 communities across four counties in western Kenya., Participants: Participants (n=2890) were ≥35 years old with diabetes (fasting glucose ≥7 mmol/L) or hypertension., Primary and Secondary Outcomes: We hypothesised that SNCs would be associated with CVD risk status (QRISK3 score). Secondary outcomes were individual CVD risk factors., Results: Among the 2890 participants, 2020 (70%) were women, and mean (SD) age was 60.7 (12.1) years. Forty-four per cent of participants had elevated QRISK3 score (≥10%). No relationship was observed between QRISK3 level and SNCs. In unadjusted comparisons, participants with any individuals in their trust network were more likely to report a good than a poor diet (41% vs 21%). SNCs for the trust and multiplex networks accounted for a substantial fraction of variation in measures of dietary quality and physical activity (statistically significant via likelihood ratio test, adjusted for false discovery rate)., Conclusion: SNCs indicative of social cohesion appear to be associated with individual behavioural CVD risk factors, although not with overall CVD risk score. Understanding how SNCs of patients with chronic diseases relate to modifiable CVD risk factors could help inform network-based interventions., Trial Registration Number: ClinicalTrials.gov identifier: NCT02501746; https://clinicaltrials.gov/ct2/show/NCT02501746., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

BACKGROUND: Emergence of HIV-1 drug resistance is at times an inevitable and anticipated consequence of antiretroviral therapy (ART) failure. We examined drug resistance patterns and virus re-suppression among subtype C-infected South African patients receiving first-line ART. METHODS: Treatment records of 431 patients on NNRTI-containing regimens for a median of 45 months were analyzed. Patients with viral load (VL) >400 copies/mL were followed and drug resistance mutations (DRM) were re-assessed. Associations between clinical/demographic measures and drug resistance/virologic outcomes were examined using Fisher exact and ordinal and logistic regression. RESULTS: Ten percent of patients (43/431) were viremic at enrollment (98% previously suppressed); sequences were obtained from 38/43. Of those, 82% had 1-7 DRM. In bivariate analysis remote exposure to single-dose nevirapine or prior ART; higher CD4 counts; lower VL; and >6 months of virologic failure were significantly associated with number of DRM. Of 25 viremic patients followed for a median of 8 months on a continued first-line regimen, 12 (48%) re-suppressed, six with K103N and three with M184V. Thirteen (52%) had continued virologic failure which was significantly associated with detectable VL>6 months prior to enrollment and number of DRM. CONCLUSION: Among these HIV-1 subtype C-infected patients, DRM numbers and patterns were associated with prior exposure to sub-optimal ART, adherence and duration of virologic failure. Viral re-suppression in the presence of K103N and M184V challenges assumptions about drug resistance. In resource-limited settings, where genotyping and alternative drug options are unavailable, continuing first-line treatment, reinforcing adherence and regular virologic monitoring may be effective even after virologic failure.