Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios in Distinguishing Lung Cancer in People with HIV.

Objective: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) demonstrate good diagnostic accuracy in distinguishing lung cancer patients from healthy individuals, primarily in HIV-negative populations. We determined the sensitivity (Se), specificity (Sp), and area under the curve (AUC) of the NLR and PLR in discriminating between people living with HIV (PLWH) with and without lung cancer. Methods: This is a comparative analysis of secondary data. Cases were PLWH with lung cancer from a retrospective cohort treated at the Uganda Cancer Institute. Controls were unmatched PLWH without lung cancer who were randomly selected from three HIV clinics in Uganda. Se, Sp, and AUC analysis and determination of optimal cutoffs were performed using receiver operating characteristic (ROC) curves. Results: Of 115 PLWH (18 cases and 97 controls), 83 (72.2%) were female, 110 (95.7) were on ART, and the median (IQR) age was 46 (38-51) years. The median (IQR) NLR was higher among cases than controls (3.53 (3.14-7.71) vs. 0.92 (0.67-1.09), p < 0.001). Similarly, the PLR was higher among cases than controls (237.5 (177.8-361.6) vs. 123.6 (100.6-155.4), p=0.001). At a cutoff of 2.44, the respective Se, Sp, and AUC of the NLR were 87.5% (95% CI: 61.7%-98.4%), 100% (95% CI: 96.2%-100%), and 0.94 (95% CI: 0.85-1.00, p < 0.001). Similarly, the respective Se, Sp, and AUC for the PLR were 75% (95% CI: 47.6%-92.7%), 87.2% (95% CI: 78.8%-93.2%), and 0.81 (95% CI: 0.70-0.93, p < 0.001) at a cutoff of 196.3. Conclusion: The NLR and PLR discriminated PLWH with and without lung cancer and could be useful in PLWH with respiratory symptoms in whom lung cancer can easily be misdiagnosed as other lung pathology.

Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults.

BACKGROUND: The Uganda Ministry of Health issued restrictive guidelines on the use of dolutegravir (DTG) in persons stratified to have a heightened risk of diabetes mellitus. This followed multiple reports of persons with HIV (PWH) presenting with accelerated hyperglycemia after a few weeks to months of exposure to DTG. Having demonstrated a low incidence of diabetes mellitus and improving blood glucose trajectories in a cohort of ART naïve Ugandan PWH on DTG, we sought to determine whether the observed improvement in blood glucose did not mask background compensated insulin resistance. METHODS: In this analysis, 63 patients underwent serial oral glucose tolerance tests over 48 weeks. Using fasting serum insulin and glucose, we calculated insulin resistance and pancreatic beta cell function by homeostatic modelling (HOMA IR and HOMA%ß respectively). Absolute mean changes between baseline and post-baseline blood glucose, pancreatic beta cell function and insulin resistance were computed by subtracting each post-baseline value from the baseline value and compared using student t-test. Multiple linear regression models were used to determine the factors associated with changes in pancreatic beta cell function and insulin resistance. RESULTS: Of the 63 participants, 37 (58%) were female. Median age was 31 (IQR: 28-37). Despite a trend towards an initial increase in both HOMA IR and HOMA%ß at 12 weeks followed by a decline through 36 weeks to 48 weeks, the HOMA IR and HOMA%ß at 48 weeks were not significantly different from baseline i.e. (difference in mean HOMA IR from baseline: 0.14, 95%CI: -0.46, 0.733, p = 0.648) and (difference in mean HOMA %ß from baseline: 6.7, 95%CI: -13.4, 26.8, p = 0.506) respectively. CONCLUSION: We demonstrated insignificant changes in both insulin resistance and pancreatic beta cell function in clinically stable young adult Ugandan PWH on dolutegravir for 48 weeks. We add to the body of evidence demonstrating glucose metabolic safety of dolutegravir in ART naïve patients. Ugandan guidelines should reconsider restricting DTG initiation in ART naive adults at high risk for diabetes.

Blood glucose outcomes of anti-retroviral therapy naïve Ugandan people with HIV with pre-diabetes mellitus initiated on dolutegravir for 48 weeks.

Background: The Uganda ministry of Health recommends frequent blood glucose monitoring for the first six months on dolutegravir, in people with HIV (PWH) having pre-diabetes mellitus (pre-DM). We sought to determine if indeed PWH with pre-diabetes started on dolutegravir had worse blood glucose outcomes at 48 weeks compared to those with normal blood glucose. Methods: In this matched cohort study, we compared 44 PWH with pre-DM and 88 PWH with normal blood glucose at baseline. The primary outcome was change in mean fasting blood glucose (FBG) from baseline to week 48 and 2-hour blood glucose (2hBG) from baseline to week 36 compared between the two groups. Results: There was significant increase in FBG in PWH with normal blood glucose (mean change in FBG(FBG): 3.9mg/dl, 95% confidence interval (95% CI): (2.2, 5.7), p value (p) = < 0.0001) and decrease in those with pre-DM (FBG: -6.1mg/dl, 95%CI (-9.1, -3.2), p = < 0.0001) at 48 weeks. 2hBG at 36 weeks was significantly lower than at baseline in both groups with the magnitude of reduction larger in those with pre-DM at 12 weeks (adjusted differences in mean drop in 2hBG (a2hBG): -19.69mg/dl, 95%CI (-30.19, -9.19), p = < 0.0001) and 36 weeks (a2hBG: -19.97mg/dl, 95%CI (-30.56, -9.39), p = < 0.0001). Conclusion: We demonstrated that Ugandan ART naïve PWH with pre-diabetes at enrollment have consistent improvement in both fasting blood glucose and glucose tolerance over 48 weeks on dolutegravir. Intensified blood glucose monitoring of these patients in the first six months of dolutegravir may be unnecessary.

Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults.

Background The Uganda Ministry of Health issued restrictive guidelines on the use of dolutegravir (DTG) in persons stratified to have a heightened risk of diabetes mellitus. This followed multiple reports of persons with HIV (PWH) presenting with accelerated hyperglycemia after a few weeks to months of exposure to DTG. Having demonstrated a low incidence of diabetes mellitus and improving blood glucose trajectories in a cohort of ART naïve Ugandan PWH on DTG, we sought to determine whether the observed improvement in blood glucose did not mask background compensated insulin resistance. Methods In this analysis, 63 patients underwent serial oral glucose tolerance tests over 48 weeks. Using fasting serum insulin and glucose, we calculated insulin resistance and pancreatic beta cell function by homeostatic modelling (HOMA IR and HOMA%ß respectively). Absolute mean changes between baseline and post-baseline blood glucose, pancreatic beta cell function and insulin resistance were computed by subtracting each post-baseline value from the baseline value and compared using student t-test. Multiple linear regression models were used to determine the factors associated with changes in pancreatic beta cell function and insulin resistance. Results Of the 63 participants, 37 (58%) were female. Median age was 31 (IQR: 28-37). Despite a trend towards an initial increase in both HOMA IR and HOMA%ß at 12 weeks followed by a decline through 36 weeks to 48 weeks, the HOMA IR and HOMA%ß at 48 weeks were not significantly different from baseline i.e. (difference in mean HOMA IR from baseline: 0.14, 95%CI: -0.46, 0.733, p = 0.648) and (difference in mean HOMA %ß from baseline: 6.7, 95%CI: -13.4, 26.8, p = 0.506) respectively.

Mycobacterium tuberculosis infection and cytogenetic abnormalities among people with HIV.

OBJECTIVE: To compare cytogenetic abnormalities among people living with HIV (PLWH) with and without previous exposure to Mycobacterium tuberculosis (Mtb) (both latent tuberculosis infection [LTBI] and active tuberculosis [TB]). METHODS: Adult PLWH (≥18 years) were randomly selected at three HIV clinics in Uganda. Previous active TB was confirmed in the clinics' TB records. LTBI was defined as a positive QuantiFERON-TB Gold Plus assay. Participants' buccal mucosal exfoliated cells were examined (per 2000 cells) using the buccal micronucleus assay for chromosomal aberrations (micronuclei and/or nuclear buds), cytokinetic defects (binucleated cells), proliferative potential (normal differentiated cells and basal cell frequency) and/or cell death (condensed chromatin, karyorrhexis, pyknotic and karyolytic cells). RESULTS: Among 97 PLWH, 42 (43.3%) had exposure to Mtb;16 had previous successfully treated active TB and 26 had LTBI. PLWH with exposure to Mtb had a higher median number of normal differentiated cells (1806.5 [1757.0 - 1842.0] vs. 1784.0 [1732.0 - 1843.0], p = 0.031) and fewer karyorrhectic cells (12.0 [9.0 - 29.0] vs. 18.0 [11.0 - 30.0], p = 0.048) than those without. PLWH with LTBI had fewer karyorrhectic cells than those without (11.5 [8.0 - 29.0] vs. 18.0 [11 - 30], p = 0.006). CONCLUSION: We hypothesized that previous exposure to Mtb is associated with cytogenetic damage among PLWH. We found that exposure to Mtb is associated with more normal differentiated cells and less frequent karyorrhexis (a feature of apoptosis). It is unclear whether this increases the propensity for tumorigenesis.

Blood glucose trajectories and incidence of diabetes mellitus in Ugandan people living with HIV initiated on dolutegravir.

BACKGROUND: Following reports of anti-retroviral therapy (ART) experienced Ugandan people living with HIV (PLHIV) presenting with diabetic ketoacidosis weeks to months following a switch to dolutegravir (DTG), the Uganda Ministry of Health recommended withholding DTG in both ART naïve and experienced PLHIV with diabetes mellitus (T2DM), as well as 3-monthly blood glucose monitoring for patients with T2DM risk factors. We sought to determine if the risk of T2DM is indeed heightened in nondiabetic ART naïve Ugandan PLHIV over the first 48 weeks on DTG. METHODS: Between January and October 2021, 243 PLHIV without T2DM were initiated on DTG based ART for 48 weeks. Two-hour oral glucose tolerance tests (2-h OGTT) were performed at baseline, 12, and 36 weeks; fasting blood glucose (FBG) was measured at 24 and 48 weeks. The primary outcome was the incidence of T2DM. Secondary outcomes included: incidence of pre-Diabetes Mellitus (pre-DM), median change in FBG from baseline to week 48 and 2-h blood glucose (2hBG) from baseline to week 36. Linear regression models were used to determine adjusted differences in FBG and 2hBG from baseline to weeks 48 and 36 respectively. RESULTS: The incidence of T2DM was 4 cases per 1000 PY (1/243) and pre-DM, 240 cases per 1000 person years (PY) (54/243). There was a significant increase in FBG from baseline to week 48 [median change from baseline (FBG): 3.6 mg/dl, interquartile range (IQR): - 3.6, 7.2, p-value (p) = 0.005] and significant reduction in 2hBG (2hBG: - 7.26 mg/dl, IQR: - 21.6, 14.4, p = 0.024) at week 36. A high CD4 count and increased waist circumference were associated with 2hBG increase at week 36. CONCLUSION: We demonstrated a low incidence of T2DM in Ugandan ART-naïve patients receiving DTG. We also demonstrated that longitudinal changes in BG were independent of conventional risk factors of T2DM in the first 48 weeks of therapy. Restricting the use of dolutegravir in Ugandan ART naïve patients perceived to be high risk for diabetes mellitus may be unwarranted.

Early culture conversion is a poor marker of treatment outcome among people with HIV and drug-resistant TB.

OBJECTIVE: Our objective was to determine associations between early (≤2 months) culture conversion (ECC) among people with HIV and drug-resistant tuberculosis (DRTB) in Uganda. METHODS: This was a countrywide retrospective cohort of people with bacteriologically confirmed DRTB and a positive baseline culture at 16 centres in Uganda between 2013 and 2019. Data were abstracted from treatment files and unit DRTB registers. Monthly sputum cultures were performed using the Lowenstein-Jensen solid medium. RESULTS: We included 664 people with DRTB and a positive baseline culture, of whom 353 (53.4%) also had HIV. Among those living with HIV, 225 (63.7%) were male and 331 (94.3%) were on antiretroviral therapy. The median month of culture conversion was 2 (interquartile range [IQR] 1-3). ECC was observed among 226 people living with HIV (64.0%; 95% confidence interval [CI] 58.9-68.9). A DRTB treatment regimen of six or more drugs was associated with ECC among people living with HIV (adjusted odds ratio [aOR]  3.82; 95% CI 1.06-13.82; p = 0.041). Cure and overall treatment success was observed among 232 (65.7%) and 269 (76.2%) people living with HIV, respectively. However, ECC was not associated with cure (crude odds ratio [OR]  0.97; 95% CI 0.61-1.54; p = 0.901), death (OR 1.12; 95% CI 0.61-2.29; p = 0.610), or overall treatment success (OR 1.29; 95% CI 0.78-2.13; p = 0.326). CONCLUSION: The majority of people living with HIV and DRTB achieve ECC. However, ECC does not predict cure, death, or treatment success. Moreover, it may require six or more drugs to achieve ECC. ECC is not an excellent indicator of the effectiveness of DRTB regimens among people living with HIV.

Prevalence of Intestinal Helminth Coinfection in Drug-Resistant Tuberculosis in Uganda.

Background: Although a third of people with tuberculosis (TB) are estimated to be coinfected with helminths, the prevalence is largely unknown among people with drug-resistant TB (DR-TB). We determined the prevalence of helminth coinfection among people with DR-TB in Uganda. Methods: In a multicenter, cross-sectional study, eligible Ugandan adults with confirmed DR-TB were consecutively enrolled between July to December 2021 at 4 treatment centers. Sociodemographic data were collected using a questionnaire. Participants underwent anthropometric and blood pressure measurements, and blood samples were evaluated for random blood glucose, glycated hemoglobin, nonfasting lipid profile, human immunodeficiency virus (HIV) infection, and a complete blood count. Fresh stool samples were evaluated for adult worms, eggs, and larvae using direct microscopy after Kato-Katz concentration techniques. Results: Of 212 participants, 156 (73.6%) were male, 118 (55.7%) had HIV, and 3 (2.8%) had malaria coinfection. The prevalence of intestinal helminth coinfection was 4.7% (10/212) (95% confidence interval, 2.6%-8.6%). The frequency of helminth infections was Ancylostoma duodenale (n = 4), Schistosoma mansoni (n = 2), Enterobius vermicularis (n = 2), Ascaris lumbricoides (n = 1), and Trichuris trichiura (n = 1). Conclusions: The prevalence of helminth coinfection was low among people with DR-TB. More studies are needed to determine the clinical relevance of helminth/DR-TB coinfection.

Cardiovascular risk factors among people with drug-resistant tuberculosis in Uganda.

BACKGROUND: Tuberculosis (TB) and its risk factors are independently associated with cardiovascular disease (CVD). We determined the prevalence and associations of CVD risk factors among people with drug-resistant tuberculosis (DRTB) in Uganda. METHODS: In this cross-sectional study, we enrolled people with microbiologically confirmed DRTB at four treatment sites in Uganda between July to December 2021. The studied CVD risk factors were any history of cigarette smoking, diabetes mellitus (DM) hypertension, high body mass index (BMI), central obesity and dyslipidaemia. We used modified Poisson regression models with robust standard errors to determine factors independently associated with each of dyslipidaemia, hypertension, and central obesity. RESULTS: Among 212 participants, 118 (55.7%) had HIV. Overall, 196 (92.5%, 95% confidence interval (CI) 88.0-95.3) had ≥ 1 CVD risk factor. The prevalence; 95% CI of individual CVD risk factors was: dyslipidaemia (62.5%; 55.4-69.1), hypertension (40.6%; 33.8-47.9), central obesity (39.3%; 32.9-46.1), smoking (36.3%; 30.1-43.1), high BMI (8.0%; 5.0-12.8) and DM (6.5%; 3.7-11.1). Dyslipidaemia was associated with an increase in glycated haemoglobin (adjusted prevalence ratio (aPR) 1.14, 95%CI 1.06-1.22). Hypertension was associated with rural residence (aPR 1.89, 95% CI 1.14-3.14) and previous history of smoking (aPR 0.46, 95% CI 0.21-0.98). Central obesity was associated with increasing age (aPR 1.02, 95%CI 1.00-1.03), and elevated diastolic blood pressure (aPR 1.03 95%CI 1.00-1.06). CONCLUSION: There is a high prevalence of CVD risk factors among people with DRTB in Uganda, of which dyslipidaemia is the commonest. We recommend integrated services for identification and management of CVD risk factors in DRTB.

Cigarette smoking is associated with an increase in blood monocytes in people with tuberculosis: A cross-sectional study.

The effect of smoking on immune responses in people with tuberculosis (TB) is not well elucidated. We aimed to compare peripheral blood counts of CD4+ and CD87 + T-lymphocytes, monocytes, and neutrophils and the CD4:CD8 ratio in TB patients with and without history of cigarette smoking. We further determined factors associated with current smoking. Participants with TB were consecutively enrolled in a cross-sectional study at a national TB treatment center in Uganda in 2018. We compared cell counts and the CD4:CD8 ratio using the median test among never smokers, past smokers (>6 months ago) and current smokers (≤6 months). Factors associated with current smoking were determined using logistic regression. A post hoc analysis for factors associated with an increase in the monocytes was also performed. Of 363 participants, there were 258 (71.1%) never smokers, 50 (13.8%) past smokers, and 55 (15.2%) current smokers. Most current smokers (49.1%) had a high sputum mycobacterial load. They also had the lowest body mass index and the highest axillary temperature. The median (interquartile range [IQR]) monocyte count among current smokers was 815 (540-1425) cells/mm3 and was significantly higher than that among past smokers (610 (350-900) cells/mm3, P = .017) and never smokers (560 [400-800] cells/mm3, P = .001). The monocyte counts positively correlated with the number of cigarettes smoked per day among current smokers (R = 0.43, P = .006). Current smokers also had higher neutrophil and CD4+ T-cell counts than never smokers. In a multivariable logistic regression model, an increase in the monocyte count was associated with current cigarette smoking (adjusted odds ratio [aOR] = 4.82, 95% confidence interval 1.61-14.39, P = .005). Similarly, current cigarette smoking was independently associated with an increase in the monocyte count (aOR = 1.80, 95% CI 1.39-2.32, P < .001). Cigarette smoking is associated with an increase in the blood monocytes in people with TB in a dose- and time-dependent manner. Further, current smoking is associated with an increase in neutrophils and CD4+ T-lymphocytes. The findings suggest that current smokers have systemic inflammation that is not necessarily beneficial to TB control in TB patients.

Turnaround time and barriers to treatment of newly diagnosed cancer in Uganda: a mixed-methods longitudinal study.

Introduction: Cancer represents a growing public health concern. Late-stage at diagnosis, limited access to effective treatment, and loss to follow-up are responsible for dismal outcomes. Objective: To describe care pathways, turnaround times, and identify barriers to timely initiation of cancer treatment. Methods: Using a sequential mixed-methods design involving focus group discussions, we followed up 50 participants between January, and June 2018. We computed the median observed turnaround time to treatment (TTT) at each care step and reported delay as deviations from the proposed ideal turnaround times. Results: The ideal TTT with either chemotherapy, or radiotherapy, or surgery was 8, 14, and 21 days respectively. At a median follow-up time of 35.5 days (IQR 17-66), only 29 of the 50 study participants had completed all steps between registration and initiation of treatment, and the observed median TTT was 16 days (9 - 22 days) for chemotherapy, and 30 days (17 - 49 days) for radiotherapy, reflecting a significant delay (p-value = 0.017). Reported barriers were; shortage of specialists, patients required visits to outside facilities for staging investigations, prohibitive costs, poor navigation system and time wastage. Conclusions: When compared to the recommended ideal turnaround time, there was significant institutional delay in access to chemotherapy and radiotherapy attributed to multiple external and internal healthcare system barriers.

Intramuscular depot medroxyprogesterone acetate accentuates bone loss associated with tenofovir disoproxil fumarate-containing antiretroviral therapy initiation in young women living with HIV (the BONE: CARE study): a prospective cohort study in Uganda.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) and intramuscular depot medroxyprogesterone acetate (DMPA-IM) are independently associated with reduced bone mineral density (BMD). We aimed to assess the combined effects of DMPA-IM use and TDF initiation on BMD in young adult women living with HIV over two years, compared with age-matched people without HIV. METHODS: Th BONE: CARE study was a prospective cohort study that recruited women aged 18-35 years from 11 HIV care and general health facilities in Kampala, Uganda. The participants were classified into four groups on the basis of their combination of HIV status, TDF use, and DMPA-IM use, as follows: women living with HIV initiating TDF-containing antiretroviral therapy (ART) with DMPA-IM (HIV positive, DMPA positive, and TDF positive); women living with HIV using DMPA-IM but not eligible for ART as per local guidelines at the time of enrolment into the study (HIV positive, DMPA positive, and TDF negative); women living with HIV initiating TDF-containing ART without DMPA-IM (HIV positive, DMPA negative, and TDF positive); and controls without HIV using non-hormonal contraceptives (HIV negative, DMPA negative, and TDF negative). BMD of the lumbar spine, total hip, and femoral neck were measured using semiannual dual-energy x-ray absorptiometry at enrolment and at intervals every 6 months thereafter. We assessed percentage change in mean BMD. FINDINGS: Between March 30, 2016, and Oct 19, 2017, we enrolled 265 women living with HIV initiating ART (159 DMPA-IM users and 106 non-hormonal contraceptive users), 187 women living with HIV using DMPA-IM but not ART, and 69 controls without HIV. Mean age was 26·1 years (SD 4·2). BMD declined significantly from baseline in women living with HIV on TDF with versus without DMPA-IM at the lumbar spine (-3·406% [95% CI -3·969 to -2·844] vs -1·111% [-1·929 to -0·293]; p<0·0001), total hip (-3·856% [-4·449 to -3·264] vs -1·714% [-2·479 to -0·949]; p=0·0002), and femoral neck (-4·422% [-5·078 to -3·766] vs -1·999% [-3·022 to -0·976]; p=0·0002), increased in controls at the lumbar spine (1·5% change), and remained unchanged at total hip and femoral neck (-0·1% change). Concurrent use of TDF and DMPA-IM resulted in significantly greater BMD decline (p<0·0001) than TDF alone (lumbar spine -2·677% [95% CI -3·743 to -1·611]; p<0·0001; total hip -2·518% [-3·575 to -1·461]; p<0·0001; and femoral neck -2·907 [-4·132 to -1·683]; p<0·0001) or than controls (lumbar spine -4·970% [-6·391 to -3·549]; p<0·0001; total hip -4·151% [-5·579 to -2·724]; p<0.0001; and femoral neck -4·773% [-6·424 to -3·122]; p<0·0001) INTERPRETATION: Concomitant DMPA-IM use resulted in a doubling of BMD loss in women living with HIV initiating TDF-containing ART. Identification of safer contraceptive and bone-sparing ART options should be prioritised for optimal care of women living with HIV. FUNDING: National Institute of Allergy and Infectious Diseases of the US National Institutes of Health.

Tuberculosis contact tracing yield and associated factors in Uganda.

BACKGROUND: The yield of tuberculosis (TB) contact tracing is historically low in Uganda. We determined factors associated with a positive contact tracing yield at an urban public TB clinic in Kampala, Uganda. METHODS: We reviewed contact tracing registers of index TB cases registered between 2015 and 2020 at Kitebi Health Center, a primary level facility. Contacts who had symptoms of TB were designated as having presumptive TB. A contact investigation that yielded a new TB case was designated as a positive yield. We used logistic regression to determine factors associated with a positive yield of contact tracing. RESULTS: Of 778 index TB cases, 455 (58.5%) had a contact investigation conducted. Index cases with a telephone contact in the unit TB register (adjusted odds ratio (aOR) 1.66, 95% CI 1.02-1.97, p = 0.036) were more likely to have a contact investigation conducted than those who did not. Of 1350 contacts, 105 (7.8%) had presumptive TB. Of these, 73 (69.5%) were further evaluated for active TB and 29 contacts had active TB. The contact tracing yield for active TB was therefore 2.1% (29/1,350). The odds of a positive yield increased tenfold with each additional presumptive contact evaluated for active TB (aOR 10.1, 95% CI 2.95-34.66, p < 0.001). Also, retreatment index TB cases were more likely to yield a positive contact (aOR 7.69 95% CI 2.08-25.00, p = 0.002) than to new cases. CONCLUSION: TB contact tracing should aim to evaluate all contacts with presumptive TB and contacts of retreatment cases to maximise the yield of contact tracing.

Undernutrition and Treatment Success in Drug-Resistant Tuberculosis in Uganda.

BACKGROUND: Undernutrition is associated with unfavourable treatment outcomes among people with drug-resistant tuberculosis (DRTB). Factors influencing the treatment outcomes among undernourished people with DRTB are not well characterised. The aim of this study was to determine factors associated with treatment success among undernourished people with DRTB in Uganda. METHODS: We analysed data from a retrospective cohort of people with DRTB from 16 treatment sites in Uganda. We included participants with a pre-treatment body mass index (BMI) of <18.5 kilograms/meters2 (kg/m2). Participants were categorised as having mild (BMI of 18.5-17 kg/m2), moderate (BMI of 16.9-16.0 kg/m2) or severe (BMI of <16.0 kg/m2) undernutrition. We performed logistic regression analysis to determine factors associated with treatment success. RESULTS: Among 473 people with DRTB, 276 (58.4%) were undernourished (BMI < 18.5 Kg/m2) and were included in the study. Of these, 92 (33.3%) had mild, 69 (25.0%) had moderate and 115 (41.7%) had severe undernutrition. The overall treatment success rate (TSR) for the undernourished was 71.4% (n = 197). Although the TSR was similar among participants with mild (71.7%), moderate (78.3%) and severe (67.0%) undernutrition (p = 0.258), all treatment failure cases (n =6) were among participants with severe undernutrition (p = 0.010). Cigarette smoking (odds ratio (OR) = 0.19, 95% CI 0.07-0.47, p < 0.001), urban residence (OR = 0.31, 95% CI 0.14-0.70, p = 0.005) and moderate (OR = 0.14, 95% CI 0.06-0.35, p < 0.001) and severe anaemia (OR = 0.06, 95% CI 0.01-0.29, p = 0.001) were associated with lower odds of treatment success. CONCLUSION: Most undernourished people with DRTB have severe undernutrition. Smoking and anaemia are modifiable factors which upon appropriate intervention could improve treatment success. The effect of urban residence on the TSR needs to be evaluated further.

Multidisciplinary management of difficult-to-treat drug resistant tuberculosis: a review of cases presented to the national consilium in Uganda.

BACKGROUND: Patients with drug resistant tuberculosis (DR-TB) with comorbidities and drug toxicities are difficult to treat. Guidelines recommend such patients to be managed in consultation with a multidisciplinary team of experts (the "TB consilium") to optimise treatment regimens. We describe characteristics and treatment outcomes of DR-TB cases presented to the national DR-TB consilium in Uganda between 2013 and 2019. METHODS: We performed a secondary analysis of data from a nation-wide retrospective cohort of DR-TB patients with poor prognostic indicators in Uganda. Patients had a treatment outcome documented between 2013 and 2019. Characteristics and treatment outcomes were compared between cases reviewed by the consilium with those that were not reviewed. RESULTS: Of 1,122 DR-TB cases, 189 (16.8%) cases from 16 treatment sites were reviewed by the consilium, of whom 86 (45.5%) were reviewed more than once. The most frequent inquiries (N = 308) from DR-TB treatment sites were construction of a treatment regimen (38.6%) and management of side effects (24.0%) while the most frequent consilium recommendations (N = 408) were a DR-TB regimen (21.7%) and "observation while on current regimen" (16.6%). Among the cases reviewed, 152 (80.4%) were from facilities other than the national referral hospital, 113 (61.1%) were aged ≥ 35 years, 72 (40.9%) were unemployed, and 26 (31.0%) had defaulted antiretroviral therapy. Additionally, 141 (90.4%) had hepatic injury, 55 (91.7%) had bilateral hearing loss, 20 (4.8%) had psychiatric symptoms and 14 (17.7%) had abnormal baseline systolic blood pressure. Resistance to second-line drugs (SLDs) was observed among 9 (4.8%) cases while 13 (6.9%) cases had previous exposure to SLDs. Bedaquiline (13.2%, n = 25), clofazimine (28.6%, n = 54), high-dose isoniazid (22.8%, n = 43) and linezolid (6.7%, n = 13) were more frequently prescribed among cases reviewed by the consilium than those not reviewed. Treatment success was observed among 126 (66.7%) cases reviewed. CONCLUSION: Cases reviewed by the consilium had several comorbidities, drug toxicities and a low treatment success rate. Consilia are important "gatekeepers" for new and repurposed drugs. There is need to build capacity of lower health facilities to construct DR-TB regimens and manage adverse effects.

Contact tracing is associated with treatment success of index tuberculosis cases in Uganda.

OBJECTIVE: To determine the effect of contact tracing on the treatment outcomes of index tuberculosis (TB) cases in Uganda. METHODS: We evaluated TB cases registered at an urban public health facility in Uganda in 2015-2020. We extracted data from the unit's TB and contact tracing registers. Treatment outcomes were classified as cure, loss to follow-up, death and treatment failure. Treatment success was the sum of cure and treatment completion. RESULTS: Among 778 TB cases, contact tracing was conducted for 455 (58.5%). Compared with cases without contract tracing (n=323), cases with contract tracing (n=455) had higher treatment success (92.5% vs 79.3%) and cure rates (57.1% vs 39.9%) and lower loss to follow-up (3.5% vs 9.3%), treatment failure (0.4% vs 1.6%) and death (3.5% vs 9.9%) (P<0.001). Contact tracing was associated with higher odds of treatment success (adjusted odds ratio (aOR) 3.00, 95% CI 1.92-4.70, P<0.001) and cure (aOR 3.11, 95% CI 1.97-4.90, P<0.001), and lower odds of loss to follow-up (aOR 0.33, (0.13-0.83), P=0.018) and death (aOR 0.38, (0.20-0.72), P=0.003). CONCLUSION: TB contact tracing should be conducted consistently not only for the benefit of identifying new TB cases but also to promote treatment success of index cases.

Treatment outcomes of drug resistant tuberculosis patients with multiple poor prognostic indicators in Uganda: A countrywide 5-year retrospective study.

BACKGROUND: Comorbid conditions and adverse drug events are associated with poor treatment outcomes among patients with drug resistant tuberculosis (DR - TB). This study aimed at determining the treatment outcomes of DR - TB patients with poor prognostic indicators in Uganda. METHODS: We reviewed treatment records of DR - TB patients from 16 treatment sites in Uganda. Eligible patients had confirmed DR - TB, a treatment outcome in 2014-2019 and at least one of 15 pre-defined poor prognostic indicators at treatment initiation or during therapy. The pre-defined poor prognostic indicators were HIV co-infection, diabetes, heart failure, malignancy, psychiatric illness/symptoms, severe anaemia, alcohol use, cigarette smoking, low body mass index, elevated creatinine, hepatic dysfunction, hearing loss, resistance to fluoroquinolones and/or second-line aminoglycosides, previous exposure to second-line drugs (SLDs), and pregnancy. Tuberculosis treatment outcomes were treatment success, mortality, loss to follow up, and treatment failure as defined by the World Health Organisation. We used logistic and cox proportional hazards regression analysis to determine predictors of treatment success and mortality, respectively. RESULTS: Of 1122 DR - TB patients, 709 (63.2%) were male and the median (interquartile range, IQR) age was 36.0 (28.0-45.0) years. A total of 925 (82.4%) had ≥2 poor prognostic indicators. Treatment success and mortality occurred among 806 (71.8%) and 207 (18.4%) patients whereas treatment loss-to-follow-up and failure were observed among 96 (8.6%) and 13 (1.2%) patients, respectively. Mild (OR: 0.57, 95% CI 0.39-0.84, p = 0.004), moderate (OR: 0.18, 95% CI 0.12-0.26, p < 0.001) and severe anaemia (OR: 0.09, 95% CI 0.05-0.17, p < 0.001) and previous exposure to SLDs (OR: 0.19, 95% CI 0.08-0.48, p < 0.001) predicted lower odds of treatment success while the number of poor prognostic indicators (HR: 1.62, 95% CI 1.30-2.01, p < 0.001), for every additional poor prognostic indicator) predicted mortality. CONCLUSION: Among DR - TB patients with multiple poor prognostic indicators, mortality was the most frequent unsuccessful outcomes. Every additional poor prognostic indicator increased the risk of mortality while anaemia and previous exposure to SLDs were associated with lower odds of treatment success. The management of anaemia among DR - TB patients needs to be evaluated by prospective studies. DR - TB programs should also optimise DR - TB treatment the first time it is initiated.

Bone Mineral Density in Antiretroviral Therapy-Naïve HIV-1-Infected Young Adult -Women Using Depot Medroxyprogesterone Acetate or Nonhormonal Contraceptives in Uganda.

Most studies evaluating BMD in human immunodeficiency virus (HIV)-infected populations have focused on antiretroviral therapy (ART)-experienced patients. In this study, the association between HIV-1 and/or depot medroxyprogesterone acetate (DMPA) and BMD among untreated HIV-1-infected women in a resource-limited setting was assessed before long-term exposure to ART. The data were then compared with that of the 2005-2008 United States National Health and Nutrition Examination Survey data for non-Hispanic White and Black women. Women aged 18-35 years, recruited from health facilities in Kampala, Uganda, were classified based on their combination of HIV-1 status and DMPA use: (i) HIV-1-infected current DMPA users, (ii) HIV-1-infected previous DMPA users, (iii) HIV-1-infected nonhormonal-contraceptive users, and (iv) HIV-uninfected nonhormonal-contraceptive users. All HIV-1-infected women reported being ART-naïve at baseline. BMD was measured at the lumbar spine, total hip, and femoral neck using DXA. Multivariate linear regression was used to assess the association between HIV-1 and/or DMPA and BMD Z-scores. Baseline data were analyzed for 452 HIV-1-infected (220 nonhormonal users, and 177 current and 55 previous DMPA users) and 69 HIV-1-uninfected nonhormonal-contraceptive users. The mean age was 26.1 years (SD, 4.2) with a median duration of DMPA use among current users of 24.0 months [medians (interquartile range), 12-48]. A higher proportion of HIV-1-infected previous (12.7%) or current DMPA users (20.3%) and nonhormonal users (15.0%) had low BMD (Z-score ≤-2 at any of the three sites) compared with age-matched HIV-1-uninfected women (2.9%). HIV-1 infection and DMPA use were independently associated with significantly lower mean BMD Z-scores at all sites, with the greatest difference being among HIV-1-infected current DMPA users (5.6%-8.0%) versus uninfected nonhormonal users. Compared with non-Hispanic White and Black women, the Ugandan local reference population had generally lower mean BMD at all sites. Newer treatment interventions are needed to mitigate BMD loss in HIV-1-infected women in resource-limited settings. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Time to first viral load testing among pregnant women living with HIV initiated on option B+ at 5 government clinics in Kampala city, Uganda: Retrospective cohort study.

BACKGROUND: Timely viral load (VL) testing is critical in the care of pregnant women living with HIV and receiving anti-retroviral therapy (ART). There is paucity of data regarding the Time to First Viral Load (TFVL) testing in resource-limited settings. METHODS: We extracted clinical and VL test data from records of a cohort of ART-naïve pregnant women living with HIV who initiated Option B + and were retained in care between 01 Jan 2015 and 31 Dec 2015. The data were verified against laboratory VL registers. TFVL (in months) was calculated based on the time difference between the date of ART initiation and FVL test. Descriptive and Cox regression analyses of data up to 30 Sep 2017 (33 months later) were done. RESULTS: Of the 622 records retrieved, 424 women were retained in care. Of 424 women retained in care, 182/424 (43%) had at least one VL result post ART initiation while 242/424 (57%) had no VL performed. Only 30/182 (16.5%) had a second VL. At six, nine, and twelve months, only 8/424 (1.9%), 47/424 (11.1%), and 94/424 (22.2%) had VL testing performed respectively post ART initiation. The median TFVL testing was 12.7 months (95 CI 11.6-13.7) post ART initiation. Across the five clinics, patient factors (age, gravidity, gestational age, marital status, and adherence at 12 months) were not significant predictors. CONCLUSION: A dismal 1.9% rate of achieving WHO-recommended TFVL testing and a median TFVL testing of twelve months post ART initiation were observed. The non-association of patient factors to these observations may suggest a serious need to review health system factors likely associated with these observations and their effective interventions.

Clinical profile and initial treatment of non-small cell lung cancer: a retrospective cohort study at the Uganda Cancer Institute.

Introduction: Lung cancer is a major global public health burden constituting 11.6% of all new cancer diagnoses and 18.4% of all cancer-related mortality. Purpose: To describe the clinical profile and initial treatment of non-small cell lung cancer in Uganda. Methods: We reviewed charts of a cohort of patients with a histologically confirmed diagnosis of non-small cell lung cancer, treated between January 2013 and November 2015 at the Uganda Cancer Institute. Results: A total of 74 patients met the inclusion criteria. The median age was 56 years (IQR 47-70), with 16.2% below the age 45 years, and 51% were female. Only 10 percent were active smokers and the most frequent histological subtype was adenocarcinoma (71%). The majority (91.9%) had stage IV disease at diagnosis and frequent metastases to contralateral lung, liver, and bones. Twenty-seven (27) patients received platinum-based chemotherapy, while 27 patients received erlotinib, and only 4 patients received palliative thoracic radiotherapy. The median survival time was 12.4 months, and the overall response rate was 32.7%. There was no survival difference by type of systemic treatment, and on multivariate analysis, poor performance status was predictive of adverse outcomes (p < 0.001). Conclusions: Patients with non-small cell lung cancer in Uganda frequently presented with late-stage disease at diagnosis. The majority of patients were female, never-smokers, and had predominantly adenocarcinoma subtype.