Treatment In Uganda Research Articles

Artemisinin-based treatment in Uganda: adverse drug reactions

Artemisinin-based treatment in Uganda: adverse drug reactions

Factors that influence delays in health care seeking, diagnosis and treatment for breast cancer patients in Uganda

Background: Cancer is a group of diseases characterized by uncontrolled growth and spread of abnormal cells, on this noted therefore breast cancer has now become the most commonly diagnosed cancer and the second leading cause of cancer related deaths among women in the Sub- Saharan Africa. The cancer incidence rate of (24%) and 50,000 deaths annually, stated that for the case of Uganda, breast cancer incidence rates almost doubled over the past 20 years. There is limited evidence on the factors which influence health care for breast cancer in Uganda. The purpose of the study was to explore the factors that influenced patient and system-related delays in health seeking, diagnosis and breast cancer treatment in Uganda.

Absence of HIV-1 Drug Resistance Mutations Supports the Use of Dolutegravir in Uganda.

To screen for drug resistance and possible treatment with Dolutegravir (DTG) in treatment-naive patients and those experiencing virologic failure during first-, second-, and third-line combined antiretroviral therapy (cART) in Uganda. Samples from 417 patients in Uganda were analyzed for predicted drug resistance upon failing a first- (N = 158), second- (N = 121), or third-line [all 51 involving Raltegravir (RAL)] treatment regimen. HIV-1 pol gene was amplified and sequenced from plasma samples. Drug susceptibility was interpreted using the Stanford HIV database algorithm and SCUEAL was used for HIV-1 subtyping. Frequency of resistance to nucleoside reverse transcriptase inhibitors (NRTIs) (95%) and non-NRTI (NNRTI, 96%) was high in first-line treatment failures. Despite lack of NNRTI-based treatment for years, NNRTI resistance remained stable in 55% of patients failing second-line or third-line treatment, and was also at 10% in treatment-naive Ugandans. DTG resistance (n = 366) was not observed in treatment-naive individuals or individuals failing first- and second-line cART, and only found in two patients failing third-line cART, while 47% of the latter had RAL- and Elvitegravir-resistant HIV-1. Secondary mutations associated with DTG resistance were found in 2%-10% of patients failing third-line cART. Of 14 drugs currently available for cART in Uganda, resistance was readily observed to all antiretroviral drugs (except for DTG) in Ugandan patients failing first-, second-, or even third-line treatment regimens. The high NNRTI resistance in first-line treatment in Uganda even among treatment-naive patients calls for the use of DTG to reach the UNAIDS 90:90:90 goals.

Treatment outcomes and tolerability of the revised WHO anti-tuberculosis drug dosages for children.

In 2010, the World Health Organization (WHO) revised the paediatric dosages of anti-tuberculosis drugs, increasing rifampicin to 15 mg/kg, isoniazid to 10 mg/kg and pyrazinamide to 35 mg/kg. We assessed treatment outcomes, safety and adherence among children treated with the new recommended dosages. Prospective cohort of children started on anti-tuberculosis treatment in Uganda with 12 months of follow-up, including alanine aminotransferase (ALT) monitoring. Treatment intake was observed. Of 144 treated children, 81 were male (56.3%), 106 (73.6%) were aged <5 years, 30 (22%) had moderate to severe malnutrition and 48 (33.3%) had human immunodeficiency virus infection. Treatment outcomes were as follows: 117 (81.3%) successes, 3 (2.1%) failures, 4 (2.8%) lost to follow-up, 19 (13.2%) deaths and 1 (0.7%) transferred out. There was no relapse. Severe malnutrition (adjusted hazard ratio 8.76, 95% confidence interval [CI] 1.59-48.25) was the only predictor of death. Two serious adverse events were attributed to treatment: one case of increased ALT and one with peripheral neuropathy. Median ALT values at baseline and at weeks 2, 4 and 8 were respectively 24 (interquartile range [IQR] 16-39), 26 (IQR 18-38), 28 (IQR 21-40) and 27 (IQR 19-38) international units/l. Treatment adherence was above 85% on all visits. We confirm the good tolerability of and adherence to the new treatment recommendations. The increased risk of fatal outcome among severely malnourished children requires attention.

Factors that influence delays in health care seeking, diagnosis and treatment for breast cancer patients in Uganda

Background: Cancer is a group of diseases characterized by uncontrolled growth and spread of abnormal cells, on this noted therefore breast cancer has now become the most commonly diagnosed cancer and the second leading cause of cancer related deaths among women in the Sub-Saharan Africa. The cancer incidence rate of (24%) and 50,000 deaths annually, stated that for the case of Uganda, breast cancer incidence rates almost doubled over the past 20 years. There is limited evidence on the factors which influence health care for breast cancer in Uganda. The purpose of the study was to explore the factors that influenced patient and system-related delays in health seeking, diagnosis and breast cancer treatment in Uganda.

Improved HIV and TB Knowledge and Competence Among Mid-level Providers in a Cluster-Randomized Trial of One-on-One Mentorship for Task Shifting.

Health worker shortages pose a challenge to the scale up of HIV care and treatment in Uganda. Training mid-level providers (MLPs) in the provision of HIV and tuberculosis (TB) treatment can expand existing health workforce capacity and access to HIV services. We conducted a cluster-randomized trial of on-site clinical mentorship for HIV and TB care at 10 health facilities in rural Uganda. Twenty MLPs at 5 randomly assigned to an intervention facilities received 8 hours a week of one-on-one mentorship, every 6 weeks over a 9-month period; and another 20 at 5 control facilities received no clinical mentorship. Enrolled MLPs' clinical knowledge and competence in management of HIV and TB was assessed using case scenarios and clinical observation at baseline and immediately after the 9-month intervention. The performance of the study health facilities on 8 TB and HIV care indicators was tracked over the 9-month period using facility patient records. Thirty-nine out 40 enrolled MLPs had case scenario and clinical observation scores for both the baseline and end of intervention assessments. Mentorship was associated with a mean score increase of 16.7% (95% confidence interval: 9.8 to 23.6, P < 0.001) for the case scenario assessments and 25.9% (95% confidence interval: 14.4 to 37.5, P < 0.001) for the clinical observations. On-site clinical mentorship was significantly associated with an overall improvement for 5 of the 8 health facility TB and HIV indicators tracked. One-on-one on-site mentorship improves individual knowledge and competence, has a downstream effect on facility performance, and is a simple approach to training MLPs for task shifting.

Absence of in vivo selection for K13 mutations after artemether\u2013lumefantrine treatment in Uganda

BackgroundIndividual drug treatment may select resistant parasites in the human body, a process termed in vivo selection. Some single nucleotide polymorphisms in Plasmodium falciparum chloroquine-resistance transporter (pfcrt) and multidrug resistance gene 1 (pfmdr1) genes have been reportedly selected after artemether–lumefantrine treatment. However, there is a paucity of data regarding in vivo selection of P. falciparum Kelch propeller domain (pfkelch13) polymorphisms, responsible for artemisinin-resistance in Asia, and six putative background mutations for artemisinin resistance; D193Y in ferredoxin, T484I in multiple resistance protein 2, V127M in apicoplast ribosomal protein S10, I356T in pfcrt, V1157L in protein phosphatase and C1484F in phosphoinositide-binding protein.MethodsArtemether–lumefantrine efficacy study with a follow-up period of 28 days was conducted in northern Uganda in 2014. The above-mentioned genotypes were comparatively analysed before drug administration and on days; 3, 7, and 28 days after treatment.ResultsIn 61 individuals with successful follow-up, artemether–lumefantrine treatment regimen was very effective with PCR adjusted efficacy of 95.2%. Among 146 isolates obtained before treatment, wild-type alleles were observed in 98.6% of isolates in pfkelch13 and in all isolates in the six putative background genes except I356T in pfcrt, which had 2.4% of isolates as mixed infections. In vivo selection study revealed that all isolates detected in the follow-up period harboured wild type alleles in pfkelch13 and the six background genes.ConclusionMutations in pfkelch13 and the six background genes may not play an important role in the in vivo selection after artemether–lumefantrine treatment in Uganda. Different mechanisms might rather be associated with the existence of parasites after treatment.

Adolescent HIV Care and Treatment in Uganda: Care Models, Best Practices and Innovations to Improve Services

Background: The number of adolescents living with HIV (ALHIV) in Uganda is growing. Improving access to HIV services among this population requires a lot of innovation. This study describes service delivery models and innovations to improve access to HIV care and treatment services by adolescents in Uganda. Methods: It was a mixed methods study in which the qualitative aspects included in-depth interviews, Focus Group Discussions and Key Informant Interviews with adolescents and various stakeholders. Quantitative data was obtained by a cross-sectional design using a questionnaire for 30 health facilities from 10 representative districts of Uganda. Results: The integrated HIV clinic model was used by 63% (19/30) of the facilities. The most preferred “Stand alone Adolescent HIV clinics” were present in only 17% (5/30). Separate adult and children’s HIV clinic models were 20% (6/30). Only 1/30 (3%) had a transition clinic. Health workers were ignorant about transition clinics but ALHIV expressed a great need for them. Only 30% (9/30) of the health facilities had Youth corners. “Peer support groups” were the commonest innovation present in 36% (9/25) of government facilities and 80% (4/5) of the private facilities. Other innovations included HIV testing at night, in schools, making community outreaches, avoiding clinic appointments during school time, use of social media, reducing waiting time, providing privacy, food, skills and transport among others. Conclusion: Stand-alone adolescent clinics are the preferred model of care for ALHIV. Youth corners in health facilities and peer support clubs were valued innovations but funding was a significant hindrance.

Economic Analysis of Severe TBI Treatment in Uganda

Introduction: Although the majority of the global burden of disease occurs in low- and middle-income countries, there is a paucity of data surveillance and analysis on the incidence of, morbidity and mortality associated with, and economic costs attributable to traumatic brain injury (TBI).Methods: A prognostic model was used to estimate outcomes of conservative and neurosurgical treatment for severe TBI based on data from a cohort of patients at the national referral hospital, Mulago Hospital, in Uganda during a 13-month study period. To evaluate the long-term impact of treatment for severe TBI, averted DALYs were calculated and converted to dollars using the human capital and the value of a statistical life (VSL) approaches. This cohort was then used as a representative sample for assessing the benefit of treating severe TBI for all of Uganda.Results: During the study period, 127 cases of severe TBI were treated averting 1,448 DALYs [0,0,0], 1,075 DALYs [3,1,0.04], or 974 DALYs [3,1,0.03]. Using the human capital approach, the economic benefit of intervention ranged from $1.3 million to $1.7 million. The VSL approach estimated an economic benefit of $282,902 to over $11 million. The health benefit of treating severe TBI for all Ugandans was estimated at between about 11,000 and 17,000 averted DALYs per year with an annual potential economic benefit of $15 to $20 million as determined with the human capital approach and $3.3 to $130 million with the VSL approach.Discussion: Treatment of severe TBI in Uganda has the potential to reduce a significant proportion of morbidity, mortality, and economic burden, which indicates the importance of treating severe TBI in developing countries.

Antiplasmodial activity and phytochemical analysis of extracts from selected Ugandan medicinal plants

Ethnopharmacological relevanceResistance of the parasites to known antimalarial drugs has provided the necessity to find new drugs from natural products against malaria. The aim of the study was to evaluate the in vitro antiplasmodial activity of some plants used by Traditional Medical Practitioners (TMPs) of Prometra and Rukararwe in malaria treatment in Uganda to provide scientific proof of the efficacies claimed by these Herbalists. Materials and methodsThe air dried samples of Clerodendrum rotundifolium (leaves), Microglossa pyrifolia (leaves), Momordica foetida (leaves) and Zanthoxylum chalybeum (stem bark) used for malaria treatment by TMPs were successively extracted with ethyl acetate, methanol and water to yield twelve extracts. The extracts were tested against the chloroquine-sensitive (NF54) and chloroquine-resistant (FCR3) Plasmodium falciparum strains in vitro using the micro Mark III test which is based on assessing the inhibition of schizont maturation. A compound A was extracted and purified from the stem bark of Z. chalybeum and its structure was identified and confirmed by spectroscopic methods. ResultsMost of the extracts tested (92%) showed an antiplasmodial activity with IC50<50µg/mL. In spite of successive extractions with different solvents, potent anti-plasmodial activity (IC50<5µg/mL) was observed in the ethyl acetate, methanol and aqueous extracts of M. pyrifolia and C. rotundifolium. Preferential enrichments of activity into water (IC50<15µg/mL) and Ethyl acetate (IC50<5µg/mL) were seen in the case of M. foetida and Z. chalybeum respectively. The most active extracts were from C. rotundifolium and M. pyrifolia with IC50 values less than 2µg/mL. Phytochemical analysis of the extracts revealed the presence of saponins, tannins, flavonoids, alkaloids and cardiac glycocides. Fagaramide isolated from Z. chalybeum had a higher activity (IC50 2.85µg/mL) against the chloroquine-resistant strain than against the chloroquine-senstive (IC50 16.6µg/mL) strain used in the study. ConclusionThe plant extracts analysed in this study presented an average antiplasmodial activity (58%). This study revealed for the first time the antiplasmodial activity of the plant C. rotundofolium. It's the first time the compound fagaramide (N-isobutyl-3-(3,4-methylene dioxyphenyl)−2E-propenamide) has been isolated from Z. chalybeum as one of the compounds that contribute to the activity of this plant against P. falciparum.

Low-Frequency Drug Resistance in HIV-Infected Ugandans on Antiretroviral Treatment Is Associated with Regimen Failure.

Most patients failing antiretroviral treatment in Uganda continue to fail their treatment regimen even if a dominant drug-resistant HIV-1 genotype is not detected. In a recent retrospective study, we observed that approximately 30% of HIV-infected individuals in the Joint Clinical Research Centre (Kampala, Uganda) experienced virologic failure with a susceptible HIV-1 genotype based on standard Sanger sequencing. Selection of minority drug-resistant HIV-1 variants (not detectable by Sanger sequencing) under antiretroviral therapy pressure can lead to a shift in the viral quasispecies distribution, becoming dominant members of the virus population and eventually causing treatment failure. Here, we used a novel HIV-1 genotyping assay based on deep sequencing (DeepGen) to quantify low-level drug-resistant HIV-1 variants in 33 patients failing a first-line antiretroviral treatment regimen in the absence of drug-resistant mutations, as screened by standard population-based Sanger sequencing. Using this sensitive assay, we observed that 64% (21/33) of these individuals had low-frequency (or minority) drug-resistant variants in the intrapatient HIV-1 population, which correlated with treatment failure. Moreover, the presence of these minority HIV-1 variants was associated with higher intrapatient HIV-1 diversity, suggesting a dynamic selection or fading of drug-resistant HIV-1 variants from the viral quasispecies in the presence or absence of drug pressure, respectively. This study identified low-frequency HIV drug resistance mutations by deep sequencing in Ugandan patients failing antiretroviral treatment but lacking dominant drug resistance mutations as determined by Sanger sequencing methods. We showed that these low-abundance drug-resistant viruses could have significant consequences for clinical outcomes, especially if treatment is not modified based on a susceptible HIV-1 genotype by Sanger sequencing. Therefore, we propose to make clinical decisions using more sensitive methods to detect minority HIV-1 variants.

HIV Drug Resistance Among Children Initiating First-Line Antiretroviral Treatment in Uganda.

Background: There are limited data on primary human immunodeficiency virus drug resistance (HIVDR) in pediatric populations. This study aimed to assess the prevalence of primary HIVDR and associated risk factors among children initiating first-line antiretroviral therapy (ART) in Uganda.Methods: At three Ugandan clinics, children (age <12 years) requiring ART were recruited between January 2010 and August 2011. Before starting ART, blood was collected for viral load and pol gene sequencing. Drug resistance mutations were determined using the 2010 International AIDS Society–USA mutation list. Risk factors for HIVDR were assessed with multivariate regression analysis.Results: Three hundred nineteen HIV-infected children with a median age of 4.9 years were enrolled. Sequencing was successful in 279 children (87.5%). HIVDR was present in 10% of all children and 15.2% of children <3 years. Nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTI (NNRTI), and dual-class resistance was present in 5.7%, 7.5%, and 3.2%, respectively. HIVDR occurred in 35.7% of prevention of mother-to-child transmission (PMTCT)–exposed children, 15.6% in children with unknown PMTCT history, and 7.7% among antiretroviral-naive children. History of PMTCT exposure [adjusted odds ratio (AOR): 2.6, 95% CI: 1.3–5.1] or unknown PMTCT status (AOR: 3.8, 95% CI: 1.1–13.5), low CD4 (AOR: 2.2, 95% CI: 1.3–3.6), current breastfeeding (AOR: 7.4, 95% CI: 2.6–21), and current maternal ART use (AOR: 6.4, 95% CI: 3.4–11.9) emerged as risk factors for primary HIVDR in multivariate analysis.Conclusion: Pretreatment HIVDR is high, especially in children with PMTCT exposure. Protease inhibitor (PI)–based regimens are advocated by the World Health Organization, but availability in children is limited. Children with (unknown) PMTCT exposure, low CD4 count, current breastfeeding, or maternal ART need to be prioritized to receive PI-based regimens.

First-line antiretroviral therapy durability in a 10-year cohort of naïve adults started on treatment in Uganda.

IntroductionThe majority of studies from resource-limited settings only report short-term virological outcomes of patients on antiretroviral treatment (ART). We aim to describe the long-term durability of first-line ART and identify factors associated with long-term virological outcomes.MethodsAt the Infectious Diseases Institute in Kampala, Uganda, 559 adult patients starting ART in 2004 were enrolled into a research cohort and monitored with viral load (VL) testing every six months for 10 years. We report the proportion and cumulative probability of 1) achieving virologic suppression (at least one VL <400 copies/ml); 2) experiencing virologic failure in patients who achieved suppression (two consecutive VLs >1000 copies/ml or one VL >5000, for those without a subsequent one); 3) treatment failure (not attaining virologic suppression or experiencing virologic failure). We used Cox regression methods to determine the characteristics associated with treatment failure. We included gender, baseline age, WHO stage, body mass index, CD4 count, propensity score for initial ART regimen, VL, time-dependent CD4 count and adherence.ResultsOf the 559 patients enrolled, 472 (84.8%) had at least one VL (67 died, 13 were lost to follow-up, 4 transferred, 2 had no VL available); 73.6% started on d4T/3TC/nevirapine and 26.4% on AZT/3TC/efavirenz. Patients in the two groups had similar characteristics, except for the higher proportion of patients in WHO Stage 3/4 and higher VL in the efavirenz-based group. Four hundred thirty-nine (93%) patients achieved virologic suppression with a cumulative probability of 0.94 (confidence interval (CI): 0.92–0.96); 74/439 (16.9%) experienced virologic failure with a cumulative probability of 0.18 (CI: 0.15–0.22). In the multivariate analysis, initial d4T/3TC/nevirapine regimen (hazard ratio (HR): 3.02; CI: 3.02 (1.66–5.44, p<0.001)) and baseline VL ≥5 log10 copies/ml (HR: 2.29; CI: 1.29–4.04) were associated with treatment failures; patients of older age (HR: 0.87 per five-year increase; CI: 0.77–0.99), with adherence >95% (HR: 0.04; CI: 0.02–0.11) and with higher time-dependent CD4 count (HR: 0.94 per 50 cells/µl increase; CI: 0.92–0.99, p<0.001) were less likely to experience treatment failure.ConclusionsThe long-term virological outcomes from this cohort are promising and comparable to those from research-rich settings. Our results provide further evidence that efavirenz is associated with better virological outcomes.

Profiling Nonrecipients of Mass Drug Administration for Schistosomiasis and Hookworm Infections: A Comprehensive Analysis of Praziquantel and Albendazole Coverage in Community-Directed Treatment in Uganda

Repeated mass drug administration (MDA) with preventive chemotherapies is the mainstay of morbidity control for schistosomiasis and soil-transmitted helminths, yet the World Health Organization recently reported that less than one-third of individuals who required preventive chemotherapies received treatment. Coverage of community-directed treatment with praziquantel (PZQ) and albendazole (ALB) was analyzed in 17 villages of Mayuge District, Uganda. National drug registers, household questionnaires, and parasitological surveys were collected to track 935 individuals before and after MDA. Multilevel logistic regressions, including household and village effects, were specified with a comprehensive set of socioeconomic and parasitological variables. The factors predicting who did not receive PZQ and ALB from community medicine distributors were identified. Drug receipt was correlated among members within a household, and nonrecipients of PZQ or ALB were profiled by household-level socioeconomic factors. Individuals were less likely to receive either PZQ or ALB if they had a Muslim household head or low home quality, belonged to the minority tribe, or had settled for more years in their village. Untreated individuals were also more likely to belong to households that did not purify drinking water, had no home latrine, and had no members who were part of the village government. The findings demonstrate how to locate and target individuals who are not treated in MDA. Infection risk factors were not informative. In particular, age, gender, and occupation were unable to identify non-recipients, although World Health Organization guidelines rely on these factors. Individuals of low socioeconomic status, minority religions, and minority tribes can be targeted to expand MDA coverage.

Patient Retention in Antiretroviral Therapy Programs up to Three Years on Treatment in Uganda, 2006–2009: A Retrospective Review

AIDS Research and Human RetrovirusesVol. 30, No. S1 Treatment as Prevention: Initiation, Adherence, and Monitoring on ARVPatient Retention in Antiretroviral Therapy Programs up to Three Years on Treatment in Uganda, 2006–2009: A Retrospective ReviewLivingstone Ssali, Charles Ngobi, Bernard Michael Etukoit, Aggrey Egessa, Celestine Bakanda, Jonathan Wangisi, and Stephen OkoboiLivingstone SsaliThe AIDS Support Organisation,TASO, Monitoring and Evaluation, Kampala, UgandaSearch for more papers by this author, Charles NgobiThe AIDS Support Organisation,TASO, Programme Management, Kampala, UgandaSearch for more papers by this author, Bernard Michael EtukoitThe AIDS Support Organisation,TASO, Programme Management, Kampala, UgandaSearch for more papers by this author, Aggrey EgessaThe AIDS Support Organisatio, TASO, Programme Management, Kampala, UgandaSearch for more papers by this author, Celestine BakandaThe AIDS Support Organisation, TASO, Planning and Strategic Information, Kampala, UgandaSearch for more papers by this author, Jonathan WangisiThe AIDS Support Organisation, TASO, Research, Kampala, UgandaSearch for more papers by this author, and Stephen OkoboiThe AIDS Support Organisation, TASO, Research, Kampala, UgandaSearch for more papers by this authorPublished Online:30 Oct 2014https://doi.org/10.1089/aid.2014.5653.abstractAboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Patient Retention in Antiretroviral Therapy Programs up to Three Years on Treatment in Uganda, 2006–2009: A Retrospective Review." AIDS Research and Human Retroviruses, 30(S1), p. A288FiguresReferencesRelatedDetails Volume 30Issue S1Oct 2014 InformationCopyright 2014, Mary Ann Liebert, Inc.To cite this article:Livingstone Ssali, Charles Ngobi, Bernard Michael Etukoit, Aggrey Egessa, Celestine Bakanda, Jonathan Wangisi, and Stephen Okoboi.Patient Retention in Antiretroviral Therapy Programs up to Three Years on Treatment in Uganda, 2006–2009: A Retrospective Review.AIDS Research and Human Retroviruses.Oct 2014.A288-A288.http://doi.org/10.1089/aid.2014.5653.abstractPublished in Volume: 30 Issue S1: October 30, 2014PDF download

Improving adherence to antiretroviral treatment in Uganda with a low-resource facility-based intervention

ObjectiveTo assess the effects of facility-based interventions using existing resources to improve overall patient attendance and adherence to antiretroviral therapy (ART) at ART-providing facilities in Uganda.MethodsThis was an interventional study which tracked attendance and treatment adherence of two distinct cohorts: experienced patients who had been on treatment for at least 12 months prior to the intervention and patients newly initiated on ART before or during the intervention. The interventions included instituting appointment system, fast-tracking, and giving longer prescriptions to experienced stable patients. Mixed-effects models were used to examine intervention effects on the experienced patients, while Cox proportional hazards models were used to determine the intervention effects on time until newly treated patients experienced gaps in medication availability.ResultsIn all, 1481 patients’ files were selected for follow-up from six facilities – 720 into the experienced cohort, and 761 into the newly treated cohort. Among patients in the experienced cohort, the interventions were associated with a significant reduction from 24.4 to 20.3% of missed appointments (adjusted odds ratio (AOR): 0.67; 95% confidence interval (CI): 0.59–0.77); a significant decrease from 20.2 to 18.4% in the medication gaps of three or more days (AOR: 0.69; 95% CI: 0.60–0.79); and a significant increase from 4.3 to 9.3% in the proportion of patients receiving more than 30 days of dispensed medication (AOR: 2.35; 95% CI: 1.91–2.89). Among newly treated patients, the interventions were associated with significant reductions of 44% (adjusted hazard rate (AHR): 0.56, 95% CI: 0.42–0.74) and 38% (AHR: 0.62; 95% CI: 0.45–0.85) in the hazards of experiencing a medication gap of 7 and 14 days or more, respectively.ConclusionsPatients’ adherence was improved with low-cost and easily implemented interventions using existing health facilities’ resources. We recommend that such interventions be considered for scale-up at national levels as measures to improve clinic attendance and ART adherence among patients in Uganda and other low-resource settings in sub-Saharan Africa.

Changes in Condom Use During the First Year of HIV Treatment in Uganda and the Relationship to Depression

We examined the effect of antiretroviral therapy (ART), and the predictive role of depression, on condom use with primary partners. Data from three studies in Uganda were combined into a sample of 750 patients with a primary sex partner, with 502 starting ART and 248 entering HIV care, and followed for 12months. Random-effects logistic regression models were used to examine the impact of ART, and the influence of baseline level and change in depression, on condom use with primary partners. At month 12, 61% ART and 67% non-ART patients were consistent condom users, compared to 44 and 41% at baseline, respectively. Multivariate analysis revealed that consistent condom use increased similarly for ART and non-ART patients, and that minor depression at baseline and increased depression over time predicted inconsistent condom use. Improved depression diagnosis and treatment could benefit HIV prevention.

The Role of Depression in Work-Related Outcomes of HIV Treatment in Uganda

The primary goal of this analysis was to examine the influence of depression above and beyond the effects of HIV treatment on work activity and function. We combined data from three longitudinal studies of patients starting antiretroviral therapy (ART) and/or entering HIV care in Uganda. Assessments were conducted at baseline and months 6 and 12. The nine-item Patient Health Questionnaire (PHQ-9) was used to assess depressive symptoms, as well as Major (scores >9) and Minor (scores 5-9) Depression status; work functioning was assessed using a subscale of the Medical Outcomes Study HIV Health Survey (MOS-HIV). Multivariate random-effects logistic regression models for longitudinal data were used to examine the impact of treatment on work status and optimal work functioning, with measures of both baseline and change in physical health functioning, cognitive functioning and depression in the models, controlling for baseline demographics, and CD4 cell count. The sample of 1,731 participants consisted of 1,204 starting ART and 527 not yet eligible for ART. At baseline, 35% were not working, and 37% had sub-optimal work functioning. Intention-to-treat analyses revealed that those on ART experienced greater improvement in both work outcomes over 12months relative to non-ART patients, and that baseline and change in physical health functioning, continuous and categorical depression were all independently associated with improvement in both work outcomes, even after accounting for the direct effect of ART. Improvement in physical and mental health plays a key role in the positive impact of HIV treatment on work activity and function, suggesting potential economic benefits of integrating depression treatment into HIV care.

A Latent Markov Modelling Approach to the Evaluation of Circulating Cathodic Antigen Strips for Schistosomiasis Diagnosis Pre- and Post-Praziquantel Treatment in Uganda

Regular treatment with praziquantel (PZQ) is the strategy for human schistosomiasis control aiming to prevent morbidity in later life. With the recent resolution on schistosomiasis elimination by the 65th World Health Assembly, appropriate diagnostic tools to inform interventions are keys to their success. We present a discrete Markov chains modelling framework that deals with the longitudinal study design and the measurement error in the diagnostic methods under study. A longitudinal detailed dataset from Uganda, in which one or two doses of PZQ treatment were provided, was analyzed through Latent Markov Models (LMMs). The aim was to evaluate the diagnostic accuracy of Circulating Cathodic Antigen (CCA) and of double Kato-Katz (KK) faecal slides over three consecutive days for Schistosoma mansoni infection simultaneously by age group at baseline and at two follow-up times post treatment. Diagnostic test sensitivities and specificities and the true underlying infection prevalence over time as well as the probabilities of transitions between infected and uninfected states are provided. The estimated transition probability matrices provide parsimonious yet important insights into the re-infection and cure rates in the two age groups. We show that the CCA diagnostic performance remained constant after PZQ treatment and that this test was overall more sensitive but less specific than single-day double KK for the diagnosis of S. mansoni infection. The probability of clearing infection from baseline to 9 weeks was higher among those who received two PZQ doses compared to one PZQ dose for both age groups, with much higher re-infection rates among children compared to adolescents and adults. We recommend LMMs as a useful methodology for monitoring and evaluation and treatment decision research as well as CCA for mapping surveys of S. mansoni infection, although additional diagnostic tools should be incorporated in schistosomiasis elimination programs.

Relapse more common than reinfection in recurrent tuberculosis 1–2 years post treatment in urban Uganda

To determine the proportion of recurrent tuberculosis (TB) due to relapse with the patient's initial strain or reinfection with a new strain of Mycobacterium tuberculosis 1-2 years after anti-tuberculosis treatment in Uganda, a sub-Saharan TB-endemic country. Records of patients with culture-confirmed TB who completed treatment at an urban Ugandan clinic were reviewed. Restriction fragment length polymorphism (RFLP) patterns were used to determine relapse or reinfection. Associations between human immunodeficiency virus (HIV) positivity and type of TB recurrence were determined. Of 1701 patients cured of their initial TB episode with a median follow-up of 1.24 years, 171 (10%) had TB recurrence (8.4 per 100 person-years). Rate and risk factors for recurrence were similar to other studies from sub-Saharan Africa. Insertion sequence (IS) 6110-based RFLP of paired isolates from 98 recurrences identified 80 relapses and 18 reinfections. Relapses among HIV-positive and -negative patients were respectively 79% and 85% of recurrences. Relapse was more common and presented earlier than reinfection in both HIV-positive and -negative TB patients 1-2 years after completing treatment. These findings impact both the choice of retreatment drug regimen, as relapsing patients are at higher risk for acquired drug resistance, and clinical trials of new TB regimens with relapse as clinical endpoint.