Computer-aided detection thresholds for digital chest radiography interpretation in tuberculosis diagnostic algorithms.

Objectives: Use of computer-aided detection (CAD) software is recommended to improve tuberculosis screening and triage, but threshold determination is challenging if reference testing has not been performed in all individuals. We aimed to determine such thresholds through secondary analysis of the 2019 Lesotho national tuberculosis prevalence survey. Methods: Symptom screening and chest radiographs were performed in participants aged ≥15 years; those symptomatic or with abnormal chest radiographs provided samples for Xpert MTB/RIF and culture testing. Chest radiographs were processed using CAD4TB version 7. We used six methodological approaches to deal with participants who did not have bacteriological test results to estimate pulmonary tuberculosis prevalence and assess diagnostic accuracy. Results: Among 17 070 participants, 5214 (31%) had their tuberculosis status determined; 142 had tuberculosis. Prevalence estimates varied between methodological approaches (0.83-2.72%). Using multiple imputation to estimate tuberculosis status for those eligible but not tested, and assuming those not eligible for testing were negative, a CAD4TBv7 threshold of 13 had a sensitivity of 89.7% (95% CI 84.6-94.8) and a specificity of 74.2% (73.6-74.9), close to World Health Organization (WHO) target product profile criteria. Assuming all those not tested were negative produced similar results. Conclusions: This is the first study to evaluate CAD4TB in a community screening context employing a range of approaches to account for unknown tuberculosis status. The assumption that those not tested are negative - regardless of testing eligibility status - was robust. As threshold determination must be context specific, our analytically straightforward approach should be adopted to leverage prevalence surveys for CAD threshold determination in other settings with a comparable proportion of eligible but not tested participants.

Piloting a new method to estimate action thresholds in medicine through intuitive weighing.

OBJECTIVES: In clinical decision-making, physicians take actions such as prescribing treatment only when the probability of disease is sufficiently high. The lowest probability at which the action will be considered, is the action threshold. Such thresholds play an important role whenever decisions have to be taken under uncertainty. However, while several methods to estimate action thresholds exist, few methods give satisfactory results or have been adopted in clinical practice. We piloted the adapted nominal group technique (aNGT), a new prescriptive method based on a formal consensus technique adapted for use in clinical decision-making. DESIGN, SETTING AND PARTICIPANTS: We applied this method in groups of postgraduate students using three scenarios: treat for rifampicin-resistant tuberculosis (RR-TB), switch to second-line HIV treatment and isolate for SARS-CoV-2 infection. INTERVENTIONS: The participants first summarise all harms of wrongly taking action when none is required and wrongly not taking action when it would have been useful. Then they rate the statements on these harms, discuss their importance in the decision-making process, and finally weigh the statements against each other. MAIN OUTCOME MEASURES: The resulting consensus threshold is estimated as the relative weights of the harms of the false positives divided by the total harm, and averaged out over participants. In some applications, the thresholds are compared with an existing method based on clinical vignettes. RESULTS: The resulting action thresholds were just over 50% for RR-TB treatment, between 20% and 50% for switching HIV treatment and 43% for COVID-19 isolation. These results were considered acceptable to all participants. Between sessions variation was low for RR-TB and moderate for HIV. Threshold estimates were moderately lower with the method based on clinical vignettes. CONCLUSIONS: The aNGT gives sensible results in our pilot and has the potential to estimate action thresholds, in an efficient manner, while involving all relevant stakeholders. Further research is needed to study the value of the method in clinical decision-making and its ability to generate acceptable thresholds that stakeholders can agree on.

Evaluation of tuberculosis diagnostic test accuracy using Bayesian latent class analysis in the presence of conditional dependence between the diagnostic tests used in a community-based tuberculosis screening study.

Diagnostic accuracy studies in pulmonary tuberculosis (PTB) are complicated by the lack of a perfect reference standard. This limitation can be handled using latent class analysis (LCA), assuming independence between diagnostic test results conditional on the true unobserved PTB status. Test results could remain dependent, however, e.g. with diagnostic tests based on a similar biological basis. If ignored, this gives misleading inferences. Our secondary analysis of data collected during the first year (May 2018 -May 2019) of a community-based multi-morbidity screening program conducted in the rural uMkhanyakude district of KwaZulu Natal, South Africa, used Bayesian LCA. Residents of the catchment area, aged ≥15 years and eligible for microbiological testing, were analyzed. Probit regression methods for dependent binary data sequentially regressed each binary test outcome on other observed test results, measured covariates and the true unobserved PTB status. Unknown model parameters were assigned Gaussian priors to evaluate overall PTB prevalence and diagnostic accuracy of 6 tests used to screen for PTB: any TB symptom, radiologist conclusion, Computer Aided Detection for TB version 5 (CAD4TBv5≥53), CAD4TBv6≥53, Xpert Ultra (excluding trace) and culture. Before the application of our proposed model, we evaluated its performance using a previously published childhood pulmonary TB (CPTB) dataset. Standard LCA assuming conditional independence yielded an unrealistic prevalence estimate of 18.6% which was not resolved by accounting for conditional dependence among the true PTB cases only. Allowing, also, for conditional dependence among the true non-PTB cases produced a 1.1% plausible prevalence. After incorporating age, sex, and HIV status in the analysis, we obtained 0.9% (95% CrI: 0.6, 1.3) overall prevalence. Males had higher PTB prevalence compared to females (1.2% vs. 0.8%). Similarly, HIV+ had a higher PTB prevalence compared to HIV- (1.3% vs. 0.8%). The overall sensitivity for Xpert Ultra (excluding trace) and culture were 62.2% (95% CrI: 48.7, 74.4) and 75.9% (95% CrI: 61.9, 89.2), respectively. Any chest X-ray abnormality, CAD4TBv5≥53 and CAD4TBv6≥53 had similar overall sensitivity. Up to 73.3% (95% CrI: 61.4, 83.4) of all true PTB cases did not report TB symptoms. Our flexible modelling approach yields plausible, easy-to-interpret estimates of sensitivity, specificity and PTB prevalence under more realistic assumptions. Failure to fully account for diagnostic test dependence can yield misleading inferences.

HIV Incidence, Recent HIV Infection, and Associated Factors, Kenya, 2007-2018.

Nationally representative surveys provide an opportunity to assess trends in recent human immunodeficiency virus (HIV) infection based on assays for recent HIV infection. We assessed HIV incidence in Kenya in 2018 and trends in recent HIV infection among adolescents and adults in Kenya using nationally representative household surveys conducted in 2007, 2012, and 2018. To assess trends, we defined a recent HIV infection testing algorithm (RITA) that classified as recently infected (<12 months) those HIV-positive participants that were recent on the HIV-1 limiting antigen (LAg)-avidity assay without evidence of antiretroviral use. We assessed factors associated with recent and long-term (≥12 months) HIV infection versus no infection using a multinomial logit model while accounting for complex survey design. Of 1,523 HIV-positive participants in 2018, 11 were classified as recent. Annual HIV incidence was 0.14% in 2018 [95% confidence interval (CI) 0.057-0.23], representing 35,900 (95% CI 16,300-55,600) new infections per year in Kenya among persons aged 15-64 years. The percentage of HIV infections that were determined to be recent was similar in 2007 and 2012 but fell significantly from 2012 to 2018 [adjusted odds ratio (aOR) = 0.31, p < .001]. Compared to no HIV infection, being aged 25-34 versus 35-64 years (aOR = 4.2, 95% CI 1.4-13), having more lifetime sex partners (aOR = 5.2, 95% CI 1.6-17 for 2-3 partners and aOR = 8.6, 95% CI 2.8-26 for ≥4 partners vs. 0-1 partners), and never having tested for HIV (aOR = 4.1, 95% CI 1.5-11) were independently associated with recent HIV infection. Although HIV remains a public health priority in Kenya, HIV incidence estimates and trends in recent HIV infection support a significant decrease in new HIV infections from 2012 to 2018, a period of rapid expansion in HIV diagnosis, prevention, and treatment.

The Feasibility and Acceptability of an mHealth Conversational Agent Designed to Support HIV Self-testing in South Africa: Cross-sectional Study.

BACKGROUND: HIV testing rates in sub-Saharan Africa remain below the targeted threshold, and primary care facilities struggle to provide adequate services. Innovative approaches that leverage digital technologies could improve HIV testing and access to treatment. OBJECTIVE: This study aimed to examine the feasibility and acceptability of Nolwazi_bot. It is an isiZulu-speaking conversational agent designed to support HIV self-testing (HIVST) in KwaZulu-Natal, South Africa. METHODS: Nolwazi_bot was designed with 4 different personalities that users could choose when selecting a counselor for their HIVST session. We recruited a convenience sample of 120 consenting adults and invited them to undertake an HIV self-test facilitated by the Nolwazi_bot. After testing, participants completed an interviewer-led posttest structured survey to assess their experience with the chatbot-supported HIVST. RESULTS: Participants (N=120) ranged in age from 18 to 47 years, with half of them being men (61/120, 50.8%). Of the 120 participants, 111 (92.5%) had tested with a human counselor more than once. Of the 120 participants, 45 (37.5%) chose to be counseled by the female Nolwazi_bot personality aged between 18 and 25 years. Approximately one-fifth (21/120, 17.5%) of the participants who underwent an HIV self-test guided by the chatbot tested positive. Most participants (95/120, 79.2%) indicated that their HIV testing experience with a chatbot was much better than that with a human counselor. Many participants (93/120, 77.5%) reported that they felt as if they were talking to a real person, stating that the response tone and word choice of Nolwazi_bot reminded them of how they speak in daily conversations. CONCLUSIONS: The study provides insights into the potential of digital technology interventions to support HIVST in low-income and middle-income countries. Although we wait to see the full benefits of mobile health, technological interventions including conversational agents or chatbots provide us with an excellent opportunity to improve HIVST by addressing the barriers associated with clinic-based HIV testing.

Implications of covariate induced test dependence on the diagnostic accuracy of latent class analysis in pulmonary tuberculosis.

Background: In application studies of latent class analysis (LCA) evaluating imperfect diagnostic tests, residual dependence among the diagnostic tests still remain even after conditioning on the true disease status due to measured variables known to affect prevalence and/or alter diagnostic test accuracy. Presence of severe comorbidities such as HIV in pulmonary tuberculosis (PTB) diagnosis alter the prevalence of PTB and affect the diagnostic performance of the available imperfect tests in use. This violates two key assumptions of LCA: (1) that the diagnostic tests are independent conditional on the true disease status (2) that the sensitivity and specificity remain constant across subpopulations. This leads to incorrect inferences. Methods: Through simulation we examined implications of likely model violations on estimation of prevalence, sensitivity and specificity among passive case-finding presumptive PTB patients with or without HIV. Jointly conditioning on PTB and HIV, we generated independent results for five diagnostic tests and analyzed using Bayesian LCA with Probit regression, separately for sets of five and three diagnostic tests using four working models allowing: (1) constant PTB prevalence and diagnostic accuracy (2) varying PTB prevalence but constant diagnostic accuracy (3) constant PTB prevalence but varying diagnostic accuracy (4) varying PTB prevalence and diagnostic accuracy across HIV subpopulations. Vague Gaussian priors with mean 1 and unknown variance were assigned to the model parameters with unknown variance assigned Inverse Gamma prior. Results: Models accounting for heterogeneity in diagnostic accuracy produced consistent estimates while the model ignoring it produces biased estimates. The model ignoring heterogeneity in PTB prevalence only is less problematic. With five diagnostic tests, the model assuming homogenous population is robust to violation of the assumptions. Conclusion: Well-chosen covariate-specific adaptations of the model can avoid bias implied by recognized heterogeneity in PTB patient populations generating otherwise dependent test results in LCA.

Feasibility of implementing the advanced HIV disease care package as part of community-based HIV/TB activities: a mixed-methods study protocol.

INTRODUCTION: Although the advanced HIV disease (AHD) care package reduces morbidity and mortality in people with AHD (defined in people living with HIV as WHO stage 3 or 4, CD4 count <200 cells/µL or age <5 years), it is barely implemented in many countries. A novel point-of-care CD4 test rapidly identifies AHD. We evaluate the feasibility of implementing the AHD care package as part of community-based HIV/tuberculosis services. METHODS AND ANALYSIS: This two-phased study is guided by the Medical Research Council framework for evaluation of complex interventions. Stage 1 is a stakeholder consultation to define tools and indicators to assess feasibility of the AHD care package. Stage 2 is the implementation of the AHD care package during a facility-based tuberculosis diagnostic accuracy study in high-burden HIV/tuberculosis settings. Consenting adults with tuberculosis symptoms in two sites in Lesotho and South Africa are eligible for inclusion. HIV-positive participants are included in the feasibility study and are offered a CD4 test, a tuberculosis-lipoarabinomannan assay and those with CD4 count of ≤200 cells/µL a cryptococcal antigen lateral flow assay. Participants are referred for clinical management following national guidelines. The evaluation includes group discussions, participant observation (qualitative strand) and a semistructured questionnaire to assess acceptability among implementers. The quantitative strand also evaluates process compliance (process rating and process cascade) and early outcomes (vital and treatment status after twelve weeks). Thematic content analysis, descriptive statistics and data triangulation will be performed. ETHICS AND DISSEMINATION: The National Health Research and Ethics Committee, Lesotho, the Human Sciences Research Council Research Ethics Committee and Provincial Department of Health, South Africa and the Ethikkommission Nordwest- und Zentralschweiz, Switzerland, approved the protocol. Dissemination will happen locally and internationally at scientific conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04666311.

A randomized clinical trial of a group cognitive-behavioral therapy to reduce alcohol use among human immunodeficiency virus-infected outpatients in western Kenya.

BACKGROUND AND AIMS: Culturally relevant and feasible interventions are needed to address limited professional resources in sub-Saharan Africa for behaviorally treating the dual epidemics of HIV and alcohol use disorder. This study tested the efficacy of a cognitive-behavioral therapy (CBT) intervention to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya. DESIGN: Randomized clinical trial. SETTING: A large HIV outpatient clinic in Eldoret, Kenya, affiliated with the Academic Model Providing Access to Healthcare collaboration. PARTICIPANTS: A total of 614 HIV-infected outpatients [312 CBT; 302 healthy life-styles (HL); 48.5% male; mean age: 38.9 years; mean education 7.7 years] who reported a minimum of hazardous or binge drinking. INTERVENTION AND COMPARATOR: A culturally adapted six-session gender-stratified group CBT intervention compared with HL education, each delivered by paraprofessionals over six weekly 90-minute sessions with a 9-month follow-up. MEASUREMENTS: Primary outcome measures were percentage of drinking days (PDD) and mean drinks per drinking day (DDD) computed from retrospective daily number of drinks data obtained by use of the time-line follow-back from baseline to 9 months post-intervention. Exploratory analyses examined unprotected sex and number of partners. FINDINGS: Median attendance was six sessions across condition. Retention at 9 months post-intervention was high and similar by condition: CBT 86% and HL 83%. PDD and DDD marginal means were significantly lower in CBT than HL at all three study phases. Maintenance period, PDD - CBT = 3.64 (0.696), HL = 5.72 (0.71), mean difference 2.08, 95% confidence interval (CI) = 0.13 - 4.04; DDD - CBT = 0.66 (0.96), HL = 0.98 (0.098), mean difference = 0.31, 95% CI = 0.05 - 0.58. Risky sex decreased over time in both conditions, with a temporary effect for CBT at the 1-month follow-up. CONCLUSIONS: A cognitive-behavioral therapy intervention was more efficacious than healthy lifestyles education in reducing alcohol use among HIV-infected Kenyan outpatient drinkers.

Decreasing incidence of pregnancy among HIV-positive adolescents in a large HIV treatment program in western Kenya between 2005 and 2017: a retrospective cohort study.

BACKGROUND: The objective of this study was to estimate the prevalence, incidence and risk factors for pregnancy among HIV-positive adolescents in a large HIV treatment program in western Kenya. METHODS: The Academic Model Providing Access to Healthcare (AMPATH) program is a partnership between Moi University, Moi Teaching and Referral Hospital and a consortium of 11 North American academic institutions. AMPATH currently provides care to 85,000 HIV-positive individuals in western Kenya. Included in this analysis were adolescents aged 10-19 enrolled in AMPATH between January 2005 and February 2017. Socio-demographic, behavioural, and clinical data at baseline and time-updated antiretroviral treatment (ART) data were extracted from the electronic medical records and summarized using descriptive statistics. Follow up time was defined as time of inclusion in the cohort until the date of first pregnancy or age 20, loss to follow up, death, or administrative censoring. Adolescent pregnancy rates and associated risk factors were determined. RESULTS: There were 8565 adolescents eligible for analysis. Median age at enrolment in HIV care was 14.0 years. Only 17.7% had electricity at home and 14.4% had piped water, both indicators of a high level of poverty. 12.9% (1104) were pregnant at study inclusion. Of those not pregnant at enrolment, 5.6% (448) became pregnant at least once during follow-up. Another 1.0% (78) were pregnant at inclusion and became pregnant again during follow-up. The overall pregnancy incidence rate was 21.9 per 1000 woman years or 55.8 pregnancies per 1000 women. Between 2005 and 2017, pregnancy rates have decreased. Adolescents who became pregnant in follow-up were more likely to be older, to be married or living with a partner and to have at least one child already and less likely to be using family planning. CONCLUSIONS: A considerable number of these HIV-positive adolescents presented at enrolment into HIV care as pregnant and many became pregnant as adolescents during follow-up. Pregnancy rates remain high but have decreased from 2005 to 2017. Adolescent-focused sexual and reproductive health and ante/postnatal care programs may have the potential to improve maternal and neonatal outcomes as well as further decrease pregnancy rates in this high-risk group.

Computer-Based Counseling Program (CARE+ Kenya) to Promote Prevention and HIV Health for People Living With HIV/AIDS: A Randomized Controlled Trial.

In countries experiencing the dual burden of HIV disease and health care worker shortages, information and communication technology tools offer the potential to help support HIV treatment adherence and secondary HIV transmission risk reduction for people living with HIV/AIDS. We conducted a randomized controlled trial (September 1, 2011-July 12, 2012) with follow-up through April 2013. Participants were recruited from two clinics affiliated with the Academic Model Providing Access to Healthcare program in western Kenya. A total of 236 participants were enrolled, randomly assigned to intervention (n = 118) or risk-assessment only control (n = 118) and followed up for 9 months. Both arms had > 0.5 log10 reduction in viral load over time (p = .0007), a clinically relevant finding. A computer-based counseling tool is feasible and acceptable in a high-volume East African HIV setting and provides evidence-based ART adherence and risk reduction support that may extend health workforce deficits.

Evaluating a patient-centred intervention to increase disclosure and promote resilience for children living with HIV in Kenya.

OBJECTIVE: We evaluated the impact of a patient-centred, culturally and age-appropriate disclosure counselling intervention on HIV disclosure rates among Kenyan children living with HIV. DESIGN: A prospective, clinic-cluster randomized trial. METHODS: We followed 285 child-caregiver dyads (children ages 10-14 years) attending eight HIV clinics (randomized to intervention or control) in Kenya. Participants at intervention clinics received intensive counselling with trained disclosure counsellors and culturally tailored materials, compared with control clinics with standard care. Disclosure was treated as a time-to-event outcome, measured on a discrete time scale, with assessments at 0, 6, 12, 18 and 24 months. Mental health and behavioural outcomes were assessed using standardized questionnaires. RESULTS: Mean age was 12.3 years [standard deviation (SD) 1.5], 52% were girls, with average time-on-treatment of 4.5 years (SD 2.4). Between 0 and 6 months, disclosure prevalence increased from 47 to 58% in the control group and from 50 to 70% in the intervention group. Differences in disclosure were not sustained over the following 18 months. The prevalence of depression symptoms was significantly higher in the intervention than in the control group at 6 months (odds ratio 2.07, 95% confidence interval 1.01-4.25); however, there was no evidence that these differences were sustained after 6 months. CONCLUSION: The clinic-based intervention increased disclosure of HIV status to children living with HIV in the short-term, resulting in earlier disclosures, but had less clear impacts longer-term. Although well tailored interventions may support disclosure, children may still experience increased levels of depression symptoms immediately following disclosure.

Viral suppression among children and their caregivers living with HIV in western Kenya.

INTRODUCTION: Despite the central role of caregivers in managing HIV treatment for children living with HIV, viral suppression within caregiver-child dyads in which both members are living with HIV is not well described. METHODS: We conducted a retrospective analysis of children living with HIV <15 years of age and their caregivers living with HIV attending HIV clinics affiliated with the Academic Model Providing Access to Healthcare (AMPATH) in Kenya between 2015 and 2017. To be included in the analysis, children and caregivers must have had ≥1 viral load (VL) during the study period while receiving antiretroviral therapy (ART) for ≥6 months, and the date of the caregiver's VL must have occurred ±90 days from the date of the child's VL. The characteristics of children, caregivers and dyads were descriptively summarized. Multivariable logistic regression was used to estimate the odds of viral non-suppression (≥ 1000 copies/mL) in children, adjusting for caregiver and child characteristics. RESULTS: Of 7667 children who received care at AMPATH during the study period, 1698 were linked to a caregiver living with HIV and included as caregiver-child dyads. For caregivers, 94% were mothers, median age at ART initiation 32.8 years, median CD4 count at ART initiation 164 cells/mm3 and 23% were not virally suppressed. For children, 52% were female, median age at ART initiation 4.2 years, median CD4 values at ART initiation were 15% (age < 5 years) and 396 cells/mm3 (age ≥ 5 years), and 38% were not virally suppressed. In the multivariable model, children were found more likely to not be virally suppressed if their caregivers were not suppressed compared to children with suppressed caregivers (aOR = 2.40, 95% CI: 1.86 to 3.10). Other characteristics associated with child viral non-suppression included caregiver ART regimen change prior to the VL, caregiver receipt of a non-NNRTI-based regimen at the time of the VL, younger child age at ART initiation and child tuberculosis treatment at the time of the VL. CONCLUSIONS: Children were at higher risk of viral non-suppression if their caregivers were not virally suppressed compared to children with suppressed caregivers. A child's viral suppression status should be closely monitored if his or her caregiver is not suppressed.

The diagnostic accuracy of Th1 (IFN-γ, TNF-α, and IL-2) and Th2 (IL-4, IL-6 and IL-10) cytokines response in AFB microscopy smear negative PTB- HIV co-infected patients.

Acid Fast Bacilli (AFB) microscopy smear remains the most widely used laboratory diagnostic technique for Pulmonary Tuberculosis (PTB) in low-and-middle income countries. Although it is highly specific, the sensitivity varies between 20-80% in immune-competent people, with only 50% case detection among HIV/TB co-infected patients, hence the need to determine the diagnostic accuracy of Th1 and Th2 cytokine response in AFB microscopy smear negative PTB-HIV co-infected patients. A total of 86 participants were recruited; 70 (81.4%) AFB microscopy smear negative and 16 (18.6%) AFB microscopy smear positive. The AFB microscopy smear negative samples were then cultured using Lowenstein Jensen Medium with 46 being culture-negative and 24 being culture-positive. Blood samples were also collected, cultured using QFT-GIT and the supernatant (plasma) harvested to evaluate cytokine profiles using Enzyme-Linked Immunosorbent Assay. IFN-γ (P < 0.001), TNF-α (P = 0.004), IL-2 (P = 0.004) and IL-4 (P = 0.009) median levels were elevated in PTB culture-positive (AFB microscopy smear negative) as compared to PTB culture-negative (AFB microscopy smear negative) participants. Finally, when Th1 cytokines (IFN-γ, TNF-α and IL-2), Th2 cytokines (IL-6 and IL-10) and T cells were included in the logistic regression fit for PTB outcome, the predictive power of discriminating between those who were AFB smear negative in the diagnosis of PTB was good with cross validated area under the curve (AUC) being 0.87 (95% CI: 0.78, 0.96). This study provides evidence for the ability of Th1 and Th2 cytokines to determine PTB status in AFB microscopy smear negative patients co-infected with HIV.

A Pilot Study of "Peer Navigators" to Promote Uptake of HIV Testing, Care and Treatment Among Street-Connected Children and Youth in Eldoret, Kenya.

Research suggests a burden of HIV among street-connected youth (SCY) in Kenya. We piloted the use of peer navigators (PNs), individuals of mixed HIV serostatus and with direct experience of being street-connected, to link SCY to HIV testing and care. From January 2015 to October 2017, PNs engaged 781 SCY (585 male, 196 female), median age 16 (IQR 13-20). At initial encounter, 52 (6.6%) were known HIV-positive and 647 (88.8%) agreed to HIV testing. Overall, 63/781 (8.1%) SCY engaged in this program were HIV-positive; 4.6% males and 18.4% females (p < 0.001). Of those HIV-positive, 48 (82.8%) initiated ART. As of October 2017, 35 (60.3%) of the HIV-positive SCY were alive and in care. The pilot suggests that PNs were successful in promoting HIV testing, linkage to care and ART initiation. More research is needed to evaluate how to improve ART adherence, viral suppression and retention in care in this population.

Randomized Phase IIA Trial of Gemcitabine Compared With Bleomycin Plus Vincristine for Treatment of Kaposi's Sarcoma in Patients on Combination Antiretroviral Therapy in Western Kenya.

PURPOSE: Kaposi's sarcoma (KS) is a spindle cell tumor resulting from growth dysregulation in the setting of infection with human herpes virus-8 (also called KS herpes virus). Advanced KS is characterized by poor responses to antiretroviral therapy and some of the chemotherapy readily accessible to patients in low-resource areas. Gemcitabine induced partial and complete regression of AIDS-associated KS (AIDS-KS) in 11 of 24 patients in a pilot study. The current study compares the antimetabolite gemcitabine with the standard care bleomycin and vincristine (BV) in the treatment of chemotherapy-naïve patients with AIDS-KS in a resource-limited setting. PATIENTS AND METHODS: Patients with persistent or progressive KS despite treatment with combined antiretroviral therapy were randomly assigned to receive gemcitabine 1,000 mg/m2 or bleomycin 15 IU/ m2 and vincristine 1.4 mg/m2 given twice weekly. The main end point was objective response by bidirectional measurement, adverse events, and quality of life after three cycles of chemotherapy. RESULTS: Of 70 participants enrolled, 36 received gemcitabine and 34 received BV. Complete response was achieved in 12 patients (33.3%) in the gemcitabine arm and six (17.6%) in the BV arm ( P = .175). The partial response rate was 52.8% (n = 19) in the gemcitabine arm and 58.8% (n = 20) in the BV arm. Both study arms reported similar neurologic and hematologic adverse events; there was statistically significant baseline to post-treatment improvement in health-related quality-of-life scores. CONCLUSION: The results of this randomized, phase IIA trial demonstrate gemcitabine activity in chemotherapy-naïve patients with AIDS-KS, on the basis of response rates, adverse events, and health-related quality-of-life scores.

Characteristics of patients with thromboembolic disorders on warfarin therapy in resource limited settings.

BACKGROUND: Warfarin is a drug with narrow therapeutic index used in the management of thromboembolic disorders. Several factors affect its plasma concentrations with a resultant risk of toxicity. We examined the database of patients on warfarin therapy in order to establish the factors that affect the stability of INR and correlated them to clinical outcomes in resource limited settings. METHODS: We analysed retrospective data of patients admitted to adult medical wards at Moi Teaching and Referral Hospital (MTRH) in 2015. Inclusion criteria were patients with thromboembolic and related disorders and on warfarin treatment. Derived data included demographics, indications for warfarin use, co-prescribed drugs, co-morbidities, INR measurements, duration of hospital stay and clinical outcomes. Descriptive statistics were used to summarize the data. Pearson's correlation coefficient was used to assess relationships between duration of hospitalization and number of INR tests. Regression splines were used to capture INR trends during the follow up period. Data was analysed using R v. 3.3.1. RESULTS: A total of 310 patients had thromboembolic disorders, out of which 63 met the study criteria. The median age was 48 years, while the mean number of INR measurements was once every four days. Majority of patients did not achieve stable INR values, with only two having consecutive INR values within therapeutic goal. Patients who died had high INR levels. The median duration of hospital stay was 9 days (IQR: 7.0, 16.5). There was a significant correlation between length of stay in hospital and the number of times that INR were measured (Corr = 0.667, p < 0.001). The two most common indications for warfarin were DVT (64.4%) and atrial fibrillation (24.7%). All the patients had one or more comorbid conditions except for 11 with DVT alone, with cardiovascular diseases and infections being the most frequent, and on concomitant medications, majority of which are known to interact with warfarin. CONCLUSIONS: It was difficult to achieve stable INR under the prevailing conditions despite the frequent tests. The potential factors that may have contributed to the fluctuations include drug-drug interactions, frequency of INR tests, comorbidities and the short duration of hospital stay.

Effect of a voice recognition system on pediatric outpatient medication errors at a tertiary healthcare facility in Kenya.

BACKGROUND: Medication-related errors account for one out of every 131 outpatient deaths, and one out of 854 inpatient deaths. The risk is threefold greater in the pediatric population. In sub-Saharan Africa, research on medication-related errors has been obscured by other health priorities and poor recognition of harm attributable to such errors.Our primary objective was to assess the effect of introduction of a voice recognition system (VRS) on the prevalence of medication errors. The secondary objective was to describe characteristics of observed medication errors and determine acceptability of VRS by clinical service providers. METHODS: This was a before-after intervention study carried out in a Pediatric Accident and Emergency Department of a private not-for-profit tertiary referral hospital in Kenya. RESULTS: A total of 1196 handwritten prescription records were examined in the pre-VRS phase and 501 in the VRS phase. In the pre-VRS phase, 74.3% of the prescriptions (889 of 1196) had identifiable errors compared with 65.7% in the VRS phase (329 of 501).More than half (58%) of participating clinical service providers expressed preference for VRS prescriptions compared with handwritten prescriptions. CONCLUSIONS: VRS reduces medication prescription errors with the greatest effect noted in reduction of incorrect medication dosages. More studies are needed to explore whether more training, user experience and software enhancement would minimize medication errors further. VRS technology is acceptable to physicians and pharmacists at a tertiary care hospital in Kenya.

Trends Over Time for Adolescents Enrolling in HIV Care in Kenya, Tanzania, and Uganda From 2001-2014.

BACKGROUND: The data needed to understand the characteristics and outcomes, over time, of adolescents enrolling in HIV care in East Africa are limited. SETTING: Six HIV care programs in Kenya, Tanzania, and Uganda. METHODS: This retrospective cohort study included individuals enrolling in HIV care as younger adolescents (10-14 years) and older adolescents (15-19 years) from 2001-2014. Descriptive statistics were used to compare groups at enrollment and antiretroviral therapy (ART) initiation over time. The proportion of adolescents was compared with the total number of individuals aged 10 years and older enrolling over time. Competing-risk analysis was used to estimate 12-month attrition after enrollment/pre-ART initiation; post-ART attrition was estimated by Kaplan-Meier method. RESULTS: A total of 6344 adolescents enrolled between 2001 and 2014. The proportion of adolescents enrolling among all individuals increased from 2.5% (2001-2004) to 3.9% (2013-2014, P < 0.0001). At enrollment, median CD4 counts in 2001-2004 compared with 2013-2014 increased for younger (188 vs. 379 cells/mm, P < 0.0001) and older (225 vs. 427 cells/mm, P < 0.0001) adolescents. At ART initiation, CD4 counts increased for younger (140 vs. 233 cells/mm, P < 0.0001) and older (64 vs. 323 cells/mm, P < 0.0001) adolescents. Twelve-month attrition also increased for all adolescents both after enrollment/pre-ART initiation (4.7% vs. 12.0%, P < 0.001) and post-ART initiation (18.7% vs. 31.2%, P < 0.001). CONCLUSIONS: Expanding HIV services and ART coverage was likely associated with earlier adolescent enrollment and ART initiation but also with higher attrition rates before and after ART initiation. Interventions are needed to promote retention in care among adolescents.

Associations with Unprotected Sexual Behavior Among HIV-Infected Drinkers in Western Kenya.

Approximately 71% of HIV-infected individuals live in sub-Saharan Africa. Alcohol use increases unprotected sex, which can lead to HIV transmission. Little research examines risky sex among HIV-infected individuals in East Africa who are not sex workers. The study purpose was to examine associations with unprotected sex in a high-risk sample of 507 HIV-infected sexually active drinkers in western Kenya. They were enrolled in a trial to reduce alcohol use. Past-month baseline alcohol use and sexual behavior were assessed using the Timeline Followback. A zero-inflated negative binomial model examined associations with occurrence and frequency of unprotected sex. Results showed heavy drinking days were significantly associated with unprotected sex occurrence across gender, and with unprotected sex frequency among women. Among women, transactional sex, alcohol-related sexual expectations, condom use self-efficacy, drinking-and-protected-sex days and age were associated with unprotected sex occurrence while alcohol-related sexual expectations, depressive symptoms and condom use self-efficacy were associated with unprotected sex frequency. Among men, alcohol-related sexual expectations, condom use self-efficacy, and age were associated with unprotected sex occurrence, while drinking-and-protected-sex days were associated with unprotected sex occurrence and frequency. Findings suggest robust relationships between heavy drinking and unprotected sex. Further research is needed elucidating the temporal relationships between drinking and unprotected sex in this population.

Retention in care among older adults living with HIV in western Kenya: A retrospective observational cohort study.

BACKGROUND: Retention, defined as continuous engagement in care, is an important indicator for quality of healthcare services. To achieve UNAIDS 90-90-90 targets, emphasis on retention as a predictor of viral suppression in patients initiated on ART is vital. Using routinely collected clinical data, the authors sought to determine the effect of age on retention post ART initiation. METHODS: De-identified electronic data for 32965 HIV-infected persons aged ≥15 years at enrolment into the Academic Model Providing Access to Healthcare program between January 2008 and December 2014 were analyzed. Follow-up time was defined from the date of ART initiation until either loss to follow-up or death or close of the database (September 2016) was observed. Proportions were compared using Pearson's Chi-square test and medians using Mann-Whitney U test. Logistic regression model was used to assess differences in ART initiation between groups, adjusting for baseline characteristics. Cox proportional hazards model adjusting for baseline characteristics and antiretroviral therapy (ART) status was used to compute hazard ratios. Kaplan-Meier survival function was used to compare retention on ART at 12, 24, and 36 months post ART initiation. RESULTS: Of the total sample, 3924 (12.0%) were aged ≥50 years at enrolment. The median (IQR) age of young adults and older adults were 32.5 (26.6, 36.9) and 54.9 (51.7, 59.9) respectively. ART initiation rates were 70.5% among older adults and 68.2% among younger adults. Retention rates in care at 12, 24 and 36 months post ART initiation were 73.9% (95% CL: 72.2, 75.5), 62.9% (95% CL: 61.0, 64.7) and 55.4% (95% CL: 53.5, 57.3) among older adults compared to 69.8% (95% CL: 69.1, 70.4), 58.1% (95% CL: 57.4, 58.8) and 49.3% (95% CL: 48.6, 50.0) among younger adults (p <0.001). A higher proportion of older adults were retained in HIV care post ART initiation compared to younger adults, Adjusted Hazard Ratio (AHR): 0.83 (95% CI: 0.78, 0.87) though they were more likely to die, AHR: 1.35 (95% CI: 1.19, 1.52). CONCLUSION: A higher proportion of older adults are initiated on ART and have better retention in care at 12, 24 and 36 months post ART initiation than younger adults. However, older adults have a higher all-cause mortality rate, perhaps partially driven by late presentation to care. Enhanced outreach and care to this group is imperative to improve their outcomes.