NRU :: Browsing by Author "Castelnuovo, Barbara"

Browsing by Author "Castelnuovo, Barbara"

Now showing 1 - 20 of 35

Antiretroviral concentration measurements as an additional tool to manage virologic failure in resource limited settings: a case control study
(AIDS research and therapy, 2019) Buzibye, Allan; Musaazi, Joseph; Braun, Amrei von; Nanzigu, Sarah; Sekaggya‑Wiltshire, Christine; Kambugu, Andrew; Fehr, Jan; Lamorde, Mohammed; Gutteck, Ursula; Muller, Daniel; Sowinski, Stefanie; Reynolds, Steven J.; Castelnuovo, Barbara
Several studies demonstrate a correlation between sub-therapeutic concentrations of antiretroviral drugs and virologic failure. We examined the sensitivity, specificity and predictive values of sub-therapeutic drug levels in predicting viralogic failure. Methods: This was a case control study with cases being samples of participants with virologic failure, and controls samples of participants with virologic suppression. We analyzed samples obtained from participants that had been on antiretroviral treatment (ART) for at least 6 months. Virologic failure was defined as HIV-RNA viral load ≥ 1000 copies/ ml. Sub-therapeutic drug levels were defined according to published reference cutoffs. The diagnostic validity of drug levels for virologic failure was assessed using plasma viral loads as a gold standard. Results: Sub-therapeutic ART concentrations explained only 38.2% of virologic failure with a probability of experiencing virologic failure of 0.66 in a patient with low drug levels versus 0.25 for participants with measurements within or above the normal range. Approximately 90% of participants with ART concentrations above the lower clinical cut off did not have virologic failure. Conclusions: These results support prior indication for therapeutic drug monitoring in cases of suspected virologic failure.
Antiretroviral Treatment Long-Term (ALT) Cohort: a prospective cohort of 10 years of ART-experienced patients in Uganda
(BMJ open, 2018) Castelnuovo, Barbara; Mubiru, Frank; Kiragga, Agnes N.; Musomba, Rachel; Mbabazi, Olive; Gonza, Paul; Kambugu, Andrew; Ratanshi, Rosalind Parks
Little information is available on patients on antiretroviral treatment (ART) after a long-term period from sub-Saharan Africa, with the longest follow-up and related outcomes being after 10 years on ART. At the Infectious Diseases Institute (IDI) (Kampala, Uganda), we set up a cohort of patients already on ART for 10 years at the time of enrolment, who will be followed up for additional 10 years.
Building clinical pharmacology laboratory capacity in low- and middle-income countries: Experience from Uganda
(African Journal of Laboratory Medicine, 2023) Omali, Denis; Buzibye, Allan; Kwizera, Richard; Byakika-Kibwika, Pauline; Namakula, Rhoda; Matovu, Joshua; Mbabazi, Olive; Mande, Emmanuel; Sekaggya-Wiltshire, Christine; Nakanjako, Damalie; Gutteck, Ursula; McAdam, Keith; Easterbrook, Philippa; Kambugu, Andrew; Fehr, Jan; Castelnuovo, Barbara; Manabe, Yukari C.; Lamorde, Mohammed; Mueller, Daniel; Merry, Concepta
Research and clinical use of clinical pharmacology laboratories are limited in low- and middle-income countries. We describe our experience in building and sustaining laboratory capacity for clinical pharmacology at the Infectious Diseases Institute, Kampala, Uganda. Intervention: Existing laboratory infrastructure was repurposed, and new equipment was acquired. Laboratory personnel were hired and trained to optimise, validate, and develop in-house methods for testing antiretroviral, anti-tuberculosis and other drugs, including 10 high-performance liquid chromatography methods and four mass spectrometry methods. We reviewed all research collaborations and projects for which samples were assayed in the laboratory from January 2006 to November 2020. We assessed laboratory staff mentorship from collaborative relationships and the contribution of research projects towards human resource development, assay development, and equipment and maintenance costs. We further assessed the quality of testing and use of the laboratory for research and clinical care. Lessons learnt: Fourteen years post inception, the clinical pharmacology laboratory had contributed significantly to the overall research output at the institute by supporting 26 pharmacokinetic studies. The laboratory has actively participated in an international external quality assurance programme for the last four years. For clinical care, a therapeutic drug monitoring service is accessible to patients living with HIV at the Adult Infectious Diseases clinic in Kampala, Uganda. Recommendations: Driven primarily by research projects, clinical pharmacology laboratory capacity was successfully established in Uganda, resulting in sustained research output and clinical support. Strategies implemented in building capacity for this laboratory may guide similar processes in other low- and middle-income countries.
Cohort profile of a study on outcomes related to tuberculosis and antiretroviral drug concentrations in Uganda: design, methods and patient characteristics of the SOUTH study
(BMJ open, 2017) Sekaggya-Wiltshire, Christine; Castelnuovo, Barbara; Braun, Amrei von; Musaazi, Joseph; Muller, Daniel; Buzibye, Allan; Gutteck, Ursula; Henning, Lars; Ledergerber, Bruno; Corti, Natascia; Lamorde, Mohammed; Fehr, Jan; Kambugu, Andrew
Tuberculosis (TB) is a leading cause of death among people living with HIV in sub-Saharan Africa. Several factors influence the efficacy of TB treatment by leading to suboptimal drug concentrations and subsequently affecting treatment outcome. The aim of this cohort is to determine the association between anti-TB drug concentrations and TB treatment outcomes. Participants Patients diagnosed with new pulmonary TB at the integrated TB-HIV outpatient clinic in Kampala, Uganda, were enrolled into the study and started on firstline anti-TB treatment. Findings to date Between April 2013 and April 2015, the cohort enrolled 268 patients coinfected with TB/HIV ; 57.8% are male with a median age of 34 years (IQR 29–40). The median time between the diagnosis of HIV and the diagnosis of TB is 2 months (IQR 0–22.5). The majority of the patients are antiretroviral therapy naive (75.4%). Our population is severely immunosuppressed with a median CD4 cell count at enrolment of 163 cells/μL (IQR 46–298). Ninety-nine per cent of the patients had a diagnosis of pulmonary TB confirmed by sputum microscopy, Xpert/RIF or culture and 203 (75.7%) have completed TB treatment with 5099 aliquots of blood collected for pharmacokinetic analysis. Future plans This cohort provides a large database of well-characterised patients coinfected with TB/HIV which will facilitate the description of the association between serum drug concentrations and TB treatment outcomes as well as provide a research platform for future substudies including evaluation of virological outcomes.
Delayed Sputum Culture Conversion in Tuberculosis– Human Immunodeficiency Virus–Coinfected Patients With Low Isoniazid and Rifampicin Concentrations
(Clinical Infectious Diseases, 2018) Sekaggya-Wiltshire, Christine; Braun, Amrei von; Lamorde, Mohammed; Ledergerber, Bruno; Buzibye, Allan; Henning, Lars; Musaazi, Joseph; Gutteck, Ursula; Denti, Paolo; Kock, Miné de; Jetter, Alexander; Byakika-Kibwika, Pauline; Eberhard, Nadia; Matovu, Joshua; Joloba, Moses; Muller, Daniel; Manabe, Yukari C.; Kamya, Moses R.; Corti, Natascia; Kambugu, Andrew; Castelnuovo, Barbara; Fehr2, Jan S.
The relationship between concentrations of antituberculosis drugs, sputum culture conversion, and treatment outcome remains unclear. We sought to determine the association between antituberculosis drug concentrations and sputum conversion among patients coinfected with tuberculosis and human immunodeficiency virus (HIV) and receiving first-line antituberculosis drugs. Methods. We enrolled HIV-infected Ugandans with pulmonary tuberculosis. Estimation of first-line antituberculosis drug concentrations was performed 1, 2, and 4 hours after drug intake at 2, 8, and 24 weeks of tuberculosis treatment. Serial sputum cultures were performed at each visit. Time-to-event analysis was used to determine factors associated with sputum culture conversion. Results. We enrolled 268 HIV-infected patients. Patients with low isoniazid and rifampicin concentrations were less likely to have sputum culture conversion before the end of tuberculosis treatment (hazard ratio, 0.54; 95% confidence interval, .37–.77; P = .001) or by the end of follow-up (0.61; .44–.85; P = .003). Patients in the highest quartile for area under the rifampicin and isoniazid concentration-time curves for were twice as likely to experience sputum conversion than those in the lowest quartile. Rifampicin and isoniazid concentrations below the thresholds and weight <55 kg were both risk factors for unfavorable tuberculosis treatment outcomes. Only 4.4% of the participants had treatment failure. Conclusion. Although low antituberculosis drug concentrations did not translate to a high proportion of patients with treatment failure, the association between low concentrations of rifampicin and isoniazid and delayed culture conversion may have implications for tuberculosis transmission.
Effect of the COVID-19 Pandemic Restrictions on Outcomes of HIV Care among Adults in Uganda
(Medicine, 2022) Izudi, Jonathan; Kiragga, Agnes; Kalyesubula, Philip; Okoboi, Stephen; Castelnuovo, Barbara
Uganda enforced several stringent restrictions such as night-time curfews, travel bans, school closure, and physical and social distancing among others that constituted a national lockdown to prevent the spread of the Coronavirus disease 2019 (COVID-19). These restrictions disrupted the delivery of health services but the impact on outcomes of human immunodeficiency virus (HIV) care has not been rigorously studied. We evaluated the effect of the COVID-19 pandemic restrictions on outcomes of HIV care among people living with HIV (PLHIV) aged ≥15 years in Kampala, Uganda. We designed a nonrandomized, quasi-experimental study using observational data retrieved from six large HIV clinics and used the data to construct two cohorts: a comparison cohort nonexposed to the restrictions and an exposed cohort that experienced the restrictions. The comparison cohort consisted of PLHIV commenced on anti-retroviral therapy (ART) between March 1, 2018, and February 28, 2019, followed for ≥1 year with outcomes assessed in March 2020, just before the restrictions were imposed. The exposed cohort comprised of PLHIV started on ART between March 1, 2019, and February 28, 2020, followed for ≥1 year with outcomes assessed in June 2021. The primary outcomes are retention, viral load testing, viral load suppression, and mortality. We employed inverse probability of treatment weighting using propensity score (IPTW-PS) to achieve comparability between the two cohorts on selected covariates. We estimated the effect of the restriction on the outcomes using logistic regression analysis weighted by propensity scores (PS), reported as odds ratio (OR) and 95% confidence interval (CI). We analyzed data for nine, 952 participants, with 5094 (51.2%) in the exposed group. The overall mean age was 32.7 ± 8.8 years. In the exposed group relative to the comparison group, viral load testing (OR, 1.68; 95% CI, 1.59–1.78) and viral load suppression (OR, 1.34; 95% CI, 1.110–1.63) increased while retention (OR, 0.76; 95% CI, 0.70–0.81) and mortality (OR, 0.75; 95% CI, 0.64–0.88) reduced. Among PLHIV in Kampala, Uganda, viral load testing and suppression improved while retention and mortality reduced during the COVID-19 pandemic restrictions due to new approaches to ART delivery and the scale-up of existing ART delivery models.
Elevated Aspergillus-specific antibody levels among HIV infected Ugandans with pulmonary tuberculosis
(BMC Pulmonary Medicine, 2017) Kwizera, Richard; Parkes-Ratanshi, Rosalind; Wiltshire, Christine Sekaggya; Musaazi, Joseph; Castelnuovo, Barbara; Kambugu, Andrew; Denning, David W.
The incidence of tuberculosis (TB) is high among human immunodeficiency virus (HIV) infected Ugandans. Recent evidence suggests that Chronic Pulmonary Aspergillosis and Aspergillus sensitisation might be responsible for significant mortality in patients treated for tuberculosis in Uganda. We retrieved and tested paired serum aliquots for 101 HIV-TB co-infected patients at the beginning and week 24 of TB treatment. We tested samples for Aspergillus-specific immunoglobulin G (IgG) and immunoglobulin E (IgE) using ImmunoCAP®; and Aspergillus-specific IgG and total serum IgE using Immulite® immunoassays. We compared antibody levels between baseline and week 24, relating them to selected baseline characteristics.10% of the patients had elevated Aspergillus-specific IgE (Aspergillus sensitization) and Aspergillus-specific IgG antibodies were elevated in 9% of the patients at the end of TB treatment. There was a significant fall in the Aspergillus-specific IgG antibody levels between baseline and week 24 (P = 0.02). Patients with cluster of differentiation 4 (CD4) T-cell count <100 cells/μl and those who were not on anti-retroviral therapy at baseline had more elevated Aspergillus-specific IgG antibodies (P = 0.01, P = 0.03). The ImmunoCAP® Aspergillus-specific IgG antibody titres were higher at week 24 than baseline with more positives at week 24; even though the difference in means was small. However, this difference was statistically significant (P = 0.02). Pulmonary infiltrates were the commonest x-ray abnormality and only 5% of the patients had pulmonary cavities on chest x-ray at week 24.These results suggest that Aspergillus infection may complicate active pulmonary TB and further studies including fungal culture and thoracic imaging may now be indicated to measure the prevalence of pulmonary aspergillosis complicating tuberculosis.
Estimating the effect of pretreatment loss to follow up on TB associated mortality at public health facilities in Uganda
(PLoS ONE, 2020) Zawedde-Muyanja, Stella; Musaazi, Joseph; Manabe, Yukari C.; Katamba, Achilles; Nankabirwa, Joaniter I.; Castelnuovo, Barbara; Cattamanchi, Adithya
Tuberculosis (TB) mortality estimates derived only from cohorts of patients initiated on TB treatment do not consider outcomes of patients with pretreatment loss to follow-up (LFU). We aimed to assess the effect of pretreatment LFU on TB-associated mortality in the six months following TB diagnosis at public health facilities in Uganda. Methods At ten public health facilities, we retrospectively reviewed treatment data for all patients with a positive Xpert®MTB/RIF test result from January to June 2018. Pretreatment LFU was defined as not initiating TB treatment within two weeks of a positive test. We traced patients with pretreatment LFU to ascertain their vital status. We performed Kaplan Meier survival analysis to compare the cumulative incidence of mortality, six months after diagnosis among patients who did and did not experience pretreatment LFU. We also determined the health facility level estimates of TB associated mortality before and after incorporating deaths prior to treatment initiation among patients who experienced pretreatment LFU. Results Of 510 patients with positive test, 100 (19.6%) experienced pretreatment LFU. Of these, we ascertained the vital status of 49 patients. In the six months following TB diagnosis, mortality was higher among patients who experienced pretreatment LFU 48.1/1000py vs 22.9/ 1000py. Hazard ratio [HR] 3.18, 95% confidence interval [CI] (1.61–6.30). After incorporating deaths prior to treatment initation among patients who experienced pretreatment LFU, health facility level estimates of TB associated mortality increased from 8.4% (95% CI 6.1%- 11.6%) to 10.2% (95% CI 7.7%-13.4%). Conclusion Patients with confirmed TB who experience pretreatment LFU have high mortality within the first six months. Efforts should be made to prioritise linkage to treatment for this group of patients. Deaths that occur prior to treatment initation should be included when reporting TB mortality in order to more accurately reflect the health impact of TB.
Factors Associated with Uptake of Contraceptives among HIV Positive Women on Dolutegravir based Anti-Retroviral Treatment at Health Centres of Kampala Capital City Authority. A cross sectional study in Uganda.
(BMC Women's Health, 2022) Mbabazi, Leah; Nabaggala, Mariah Sarah; Kiwanuka, Suzanne; Kiguli, Juliet; Okoboi, Stephen; Laker, Eva; Castelnuovo, Barbara; Lamorde, Mohammed; Kiconco, Arthur; Amperiize, Mathius
In May 2018, the World Health Organisation issued a teratogenicity alert for HIV positive women using dolutegravir (DTG) and emphasised increased integration of sexual and reproductive services into HIV care to meet contraceptive needs of HIV positive women. However, there are scarce data on the impact of this guidance on contraceptive uptake. Objective To investigate the uptake of contraceptives and the factors affecting the uptake of contraceptive services among the HIV positive women of reproductive age who use DTG. Methods A cross-sectional survey was conducted from April 2019 to July 2019, in five government clinics in central Uganda where DTG was offered as the preferred first-line antiretroviral treatment (ART) regimen. We randomly selected 359 non-pregnant women aged 15-49 years using DTG-based regimens. We used interviewer administered questionnaires to collect data on demographics, contraceptive use, social and health system factors. We defined contraceptive uptake as the proportion of women using any method of contraception divided by the total number of women on DTG during the review period. We described patients’ characteristics using descriptive statistics. Factors associated with contraceptive uptake were investigated using Poisson regression at multivariable analysis (STATA 14). Results Of the 359 participants, the mean age was 37(SD=6.8), half 50.7% had attained primary level of education and average monthly income <100,000Ushs. The overall level of Contraceptive uptake was 38.4%, modern contraceptive uptake was 37.6% and 96.4% of the participants had knowledge of contraceptives. The most utilised method was the injectable at 58.4% followed by condoms 15%, IUD 10.7%, pills 6.4%, implants 5.4%, and least used was sterilization at 0.7%. Predictor factors that increased likelihood of contraceptive uptake were; religion of others category AIRR=1.53(95% CI: 1.01, 2.29) and parity 3-4 children AIRR=1.48(95% CI: 1.14, 1.92). Reduced rates were observed for age 40-49 years AIRR=0.45(95% CI: 0.21, 0.94), unemployment AIRR 0.63(95% CI: 0.42, 0.94), not discussing FP with partner AIRR=0.39(95% CI: 0.29, 0.52) and not receiving FP counselling AIRR=2.86 (95% CI: 0.12, 0.73). Non-significant variables were facility, education level, marital status, sexual activity, experienced side effects of FP and knowledge on both contraceptives and DTG. Conclusion This study shows a low-level uptake of contraceptives and injectable was the most used method. It also indicated that FP counselling and partner discussion on FP increased contraceptive uptake. Therefore, more strategies should be put in place to increase male involvement in family planning programs and scale up the integration of family planning services into HIV care and management programs.
Feasibility of a multifaceted intervention to improve treatment initiation among patients diagnosed with TB using Xpert MTB/RIF testing in Uganda
(PLoS ONE, 2022) Zawedde-Muyanja, Stella; Musaazi, Joseph; Castelnuovo, Barbara; Cattamanchi, Adithya; Katamba, Achilles; Manabe, Yukari C.
One in five patients diagnosed with TB in Uganda are not initiated on TB treatment within two weeks of diagnosis. We evaluated a multifaceted intervention for improving TB treatment initiation among patients diagnosed with TB using Xpert® MTB/RIF testing in Uganda. Methods This was a pre-post interventional study at one tertiary referral hospital. The intervention was informed by the COM-B model and included; i) medical education sessions to improve healthcare worker knowledge about the magnitude and consequences of pretreatment loss to follow-up; ii) modified laboratory request forms to improve recording of patient contact information; and iii) re-designed workflow processes to improve timeliness of sputum testing and results dissemination. TB diagnostic process and outcome data were collected and compared from the period before (June to August 2019) and after (October to December 2019) intervention initiation. Results In September 2019, four CME sessions were held at the hospital and were attended by 58 healthcare workers. During the study period, 1242 patients were evaluated by Xpert® MTB/ RIF testing at the hospital (679 pre and 557 post intervention). Median turnaround time for sputum test results improved from 12 hours (IQR 4–46) in the pre-intervention period to 4 hours (IQR 3–6) in the post-intervention period. The proportion of patients started on treatment within two weeks of diagnosis improved from 59% (40/68) to 89% (49/55) (difference 30%, 95% CI 14%-43%, p<0.01) while the proportion of patients receiving a same-day diagnosis increased from 7.4% (5/68) to 25% (14/55) (difference 17.6%, 95% CI 3.9%- 32.7%, p<0.01). Conclusion The multifaceted intervention was feasible and resulted in a higher proportion of patients initiating TB treatment within two weeks of diagnosis.
High efavirenz serum concentrations in TB/HIV-coinfected Ugandan adults with a CYP2B6 516 TT genotype on anti-TB treatment
(Journal of Antimicrobial Chemotherapy, 2019) Braun, Amrei von; Castelnuovo, Barbara; Ledergerber, Bruno; Cusato, Jessica; Buzibye, Allan; Kambugu, Andrew; Fehr, Jan; Calcagno, Andrea; Lamorde, Mohammed; Sekaggya-Wiltshire, Christine
To report the efavirenz serumconcentrations in TB/HIV-coinfected Ugandan adults on concomitant anti-TB treatment and analyse factors associated with elevated concentrations in this specific population. Methods: Serum efavirenz concentrations in TB/HIV-coinfected Ugandan adults on efavirenz-based ART (600mg daily) were measured onsite at 2, 8, 12 and 24 weeks of concomitant anti-TB treatment, including rifampicin. Genetic analysis was done retrospectively through real-time PCR by allelic discrimination (CYP2B6 516G.T, rs3745274). Univariable and multivariable logistic regression analyses were done to assess factors potentially associated with elevated efavirenz serum concentrations. Results: A total of 166 patients were included in the analysis. The median age was 34 (IQR"30–40) years, 99 (59.6%) were male, the median CD4 cell count was 195 (IQR"71–334) cells/mm3 and the median BMI was 19 (IQR"17.6–21.5) kg/m2. Almost half of all patients (82, 49.4%) had at least one efavirenz serum concentration above the reference range of 4 mg/L. The serum efavirenz concentrations of patients with genotype CYP2B6 516 TT were consistently above 4 mg/L and significantly higher than those of patients with GG/GT genotypes: CYP2B6 516 TT 9.6 mg/L (IQR"7.3–13.3) versus CYP2B6 516 GT 3.4 mg/L (IQR"2.1–5.1) and CYP2B6 516 GG 2.6 mg/L (IQR"1.3–4.0) (Wilcoxon rank-sumtest: P,0.0001). Conclusions: A large proportion of our study participants had at least one efavirenz serum concentration .4 mg/L. The CYP2B6 516 TT genotype was the strongest predictor of high concentration. Physicians should be vigilant that efavirenz serum concentrations may be elevated in patients on concomitant anti-TB treatment and that individualized care is warranted whenever possible.
“I Felt very Small and Embarrassed by the Health Care Provider When I Requested to be Tested for Syphilis”: Barriers And Facilitators of Regular Syphilis and HIV Testing among Female Sex Workers in Uganda
(BMC Public Health, 2021) Muhindo, Richard; Mujugira, Andrew; Castelnuovo, Barbara; Sewankambo, Nelson K.; Ratanshi, Rosalind Parkes; Tumwesigye, Nazarius Mbona; Joloba, Edith Nakku; Kiguli, Juliet
Periodic testing of female sex workers (FSW) for sexually transmitted infections (STIs) is a core component of global and national responses to achieve population-level STI elimination. We conducted a qualitative study to explore barriers and facilitators of regular syphilis and HIV testing among FSW in Uganda.Within a quasi-experimental study among 436 FSW to assess the effect of peer education and text message reminders on uptake of regular STI and HIV testing among FSW, we conducted 48 qualitative interviews in four cities in Uganda from August–December 2018. We purposively selected FSW who tested for syphilis and HIV every 3–6 months; 12 FSW were interviewed in each city. Sex worker interviews explored: 1) reasons for periodic syphilis and HIV testing; 2) barriers and facilitators of testing; 3) experiences of testing; and 4) challenges faced while seeking testing services. Data were analyzed using thematic content analysis.Thematic analysis revealed individual- and health system-level barriers and facilitators of testing. For syphilis, barriers were a) interpersonal stigma, low perceived severity of syphilis and testing misconceptions (individual); and b) judgmental provider attitudes, paucity of facilities offering syphilis testing, stockouts of test kits and high cost (health system). Facilitators were c) desire to remain healthy, get married and have children, knowing the benefits of early treatment, influence of male partners/clients and normative testing behaviors (individual); and d) sex worker clinics offering dual syphilis/HIV testing (health system). For HIV, barriers included: a) internalized stigma (individual); and b) unfavorable clinic hours, stigma, discrimination, and unfriendly provider (health system). Facilitators were a) motivations to stay healthy and attract clients, habitual testing, self-efficacy, doubts about accuracy of negative test results, and use of post-exposure prophylaxis (individual); and d) availability of testing facilities (health system). Syphilis and HIV had similar testing barriers and facilitators.HIV programs are likely to be important entry points for syphilis testing among FSW. Multi-level interventions to address testing barriers should consider focusing on these service delivery points. Extending the dual syphilis and HIV testing approach to FSW may improve testing uptake for both infections at public health facilities and decrease population-level incidence.
Implementation of Provider-Based Electronic Medical Records and Improvement of the Quality of Data in a Large HIV Program in Sub-Saharan Africa
(PLoS ONE, 2012) Castelnuovo, Barbara; Kiragga, Agnes; Afayo, Victor; Ncube, Malisa; Orama, Richard; Magero, Stephen; Okwi, Peter; Manabe, Yukari C.; Kambugu, Andrew
Starting in June 2010 the Infectious Diseases Institute (IDI) clinic (a large urban HIV out-patient facility) switched to provider-based Electronic Medical Records (EMR) from paper EMR entered in the database by data-entry clerks. Standardized clinics forms were eliminated but providers still fill free text clinical notes in physical patients’ files. The objective of this study was to compare the rate of errors in the database before and after the introduction of the providerbased EMR. Methods and Findings: Data in the database pre and post provider-based EMR was compared with the information in the patients’ files and classified as correct, incorrect, and missing. We calculated the proportion of incorrect, missing and total error for key variables (toxicities, opportunistic infections, reasons for treatment change and interruption). Proportions of total errors were compared using chi-square test. A survey of the users of the EMR was also conducted. We compared data from 2,382 visits (from 100 individuals) of a retrospective validation conducted in 2007 with 34,957 visits (from 10,920 individuals) of a prospective validation conducted in April–August 2011. The total proportion of errors decreased from 66.5% in 2007 to 2.1% in 2011 for opportunistic infections, from 51.9% to 3.5% for ART toxicity, from 82.8% to 12.5% for reasons for ART interruption and from 94.1% to 0.9% for reasons for ART switch (all P,0.0001). The survey showed that 83% of the providers agreed that provider-based EMR led to improvement of clinical care, 80% reported improved access to patients’ records, and 80% appreciated the automation of providers’ tasks. Conclusions: The introduction of provider-based EMR improved the quality of data collected with a significant reduction in missing and incorrect information. The majority of providers and clients expressed satisfaction with the new system. We recommend the use of provider-based EMR in large HIV programs in Sub-Saharan Africa.
Increasing retention of HIV positive pregnant and breastfeeding mothers on option-b plus by upgrading and providing full time HIV services at a lower health facility in rural Uganda
(BMC public health, 2019) Mirembe Masereka, Enosk; Ngabirano, Tom Denis; Osingada, Charles Peter; Sekaggya Wiltshire, Christine; Castelnuovo, Barbara; Kiragga, Agnes N.
Despite advancement in Prevention of Mother to Child Transmission (PMTCT) services, the rate of MTCT of HIV in sub-Saharan Africa is still high. This is partly due to low retention of HIV positive mothers in HIV care. We sought to determine the level of retention and the factors associated with retention among HIV positive pregnant and breastfeeding mothers following accreditation of an antiretroviral therapy (ART) clinic to offer full time ART services in one of the lower health facilities in rural Western Uganda. This study was a mixed methods study conducted in 5 health centres in rural Western Uganda from 10th April to 10th May 2017. A total of 132 retained and non-retained HIV positive pregnant and breastfeeding mothers were recruited. A Mother was categorized as retained if she had not missed her ART appointments at antenatal or postnatal clinic for ≥3 consecutive months. Questionnaires were administered and four focus group discussions were held. We used descriptive statistics to understand characteristics of mothers and their levels of retention. Thematic analysis was used to analyze qualitative data.
An Interactive Voice Response Software to Improve the Quality of Life of People Living With HIV in Uganda: Randomized Controlled Trial
(JMIR mHealth and uHealth, 2021) Byonanebye, Dathan Mirembe; Nabaggala, Maria S.; Naggirinya, Agnes Bwanika; Lamorde, Mohammed; Oseku, Elizabeth; King, Rachel; Owarwo, Noela; Laker, Eva; Orama, Richard; Castelnuovo, Barbara; Kiragga, Agnes; Ratanshi, Rosalind Parkes
Following the successful scale-up of antiretroviral therapy (ART), the focus is now on ensuring good quality of life (QoL) and sustained viral suppression in people living with HIV. The access to mobile technology in the most burdened countries is increasing rapidly, and therefore, mobile health (mHealth) technologies could be leveraged to improve QoL in people living with HIV. However, data on the impact of mHealth tools on the QoL in people living with HIV are limited to the evaluation of SMS text messaging; these are infeasible in high-illiteracy settings.The primary and secondary outcomes were to determine the impact of interactive voice response (IVR) technology on Medical Outcomes Study HIV QoL scores and viral suppression at 12 months, respectively.Within the Call for Life study, ART-experienced and ART-naïve people living with HIV commencing ART were randomized (1:1 ratio) to the control (no IVR support) or intervention arm (daily adherence and pre-appointment reminders, health information tips, and option to report symptoms). The software evaluated was Call for Life Uganda, an IVR technology that is based on the Mobile Technology for Community Health open-source software. Eligibility criteria for participation included access to a phone, fluency in local languages, and provision of consent. The differences in differences (DIDs) were computed, adjusting for baseline HIV RNA and CD4.Overall, 600 participants (413 female, 68.8%) were enrolled and followed-up for 12 months. In the intervention arm of 300 participants, 298 (99.3%) opted for IVR and 2 (0.7%) chose SMS text messaging as the mode of receiving reminders and health tips. At 12 months, there was no overall difference in the QoL between the intervention and control arms (DID=0.0; P=.99) or HIV RNA (DID=0.01; P=.94). At 12 months, 124 of the 256 (48.4%) active participants had picked up at least 50% of the calls. In the active intervention participants, high users (received >75% of reminders) had overall higher QoL compared to low users (received <25% of reminders) (92.2 versus 87.8, P=.02). Similarly, high users also had higher QoL scores in the mental health domain (93.1 versus 86.8, P=.008) and better appointment keeping. Similarly, participants with moderate use (51%-75%) had better viral suppression at 12 months (80/94, 85% versus 11/19, 58%, P=.006).Overall, there was high uptake and acceptability of the IVR tool. While we found no overall difference in the QoL and viral suppression between study arms, people living with HIV with higher usage of the tool showed greater improvements in QoL, viral suppression, and appointment keeping. With the declining resources available to HIV programs and the increasing number of people living with HIV accessing ART, IVR technology could be used to support patient care. The tool may be helpful in situations where physical consultations are infeasible, including the current COVID epidemic.
Is it safe to switch from stavudine to zidovudine after developing symptomatic hyperlactatemia?
(African Health Sciences, 2008) Castelnuovo, Barbara; Nanyonjo, Agnes; Kamya, Moses; Ocama, Ponsiano
In resource limited settings patients on antiretroviral treatment who develop stavudine induced hyperlactatemia are often switched to zidovudine on the basis of published studies that demonstrate that this agent can be a safe alternative. Case report: We describe here a case of a 60 year old female that experienced a relapse of symptomatic hyperlactatemia after being switched from stavudine to zidovudine and how the case was managed at the Infectious Diseases Institute, Kampala, Uganda. Discussion: This case shows that switching to zidovudine potentially can lead to a hyperlactatemia relapse. Therefore we recommend close follow up for patients that are switched from stavudine to zidovudine and, in case lactate measurement is not possible, free programs should provide safer drugs such as abacavir and tenofovir for patients that develop hyperlactatemia.
Low Antituberculosis Drug Concentrations in HIV-Tuberculosis- Coinfected Adults with Low Body Weight: Is It Time To Update Dosing Guidelines?
(Antimicrob Agents Chemother, 2019) Sekaggya-Wiltshire, Christine; Chirehwa, Maxwell; Musaazi, Joseph; Braun, Amrei von; Buzibye, Allan; Muller, Daniel; Gutteck, Ursula; Motta, Ilaria; Calcagno, Andrea; Fehr, Jan S.; Kambugu, Andrew; Castelnuovo, Barbara; Lamorde, Mohammed; Denti, Paolo
Antituberculosis drugs display large pharmacokinetic variability, which may be influenced by several factors, including body size, genetic differences, and drug-drug interactions. We set out to determine these factors, quantify their effect, and determine the dose adjustments necessary for optimal drug concentrations. HIVinfected Ugandan adults with pulmonary tuberculosis treated according to international weight-based dosing guidelines underwent pharmacokinetic sampling (1, 2, and 4 h after drug intake) 2, 8, and 24 weeks after treatment initiation. Between May 2013 and November 2015, we enrolled 268 patients (148 males) with a median weight of 53.5 (interquartile range [IQR], 47.5 to 59.0) kg and a median age of 35 (IQR, 29 to 40) years. Population pharmacokinetic modeling was used to interpret the data and revealed that patients weighing 55 kg achieved lower concentrations than those in higher weight bands for all drugs in the regimen. The models predicted that this imbalance could be solved with a dose increment of one fixed-dose combination (FDC) tablet for the weight bands of 30 to 37 and 38 to 54 kg. Additionally, the concomitant use of efavirenz increased isoniazid clearance by 24.1%, while bioavailability and absorption of rifampin and isoniazid varied up to 30% in patients on different formulations. Current dosing guidelines lead to lower drug exposure in patients in the lower weight bands. Simply adding one FDC tablet to current weight band-based dosing would address these differences in exposure and possibly improve outcomes. Lower isoniazid exposures due to efavirenz deserve further attention, as does the quality of currently used drug formulations of anti-TB drugs. (This study has been registered at ClinicalTrials.gov under identifier NCT01782950.)
Low Bone Mass In People Living With HIV On Long-Term Anti-Retroviral Therapy: A Single Center Study In Uganda
(PloS one, 2021) Mwaka, Erisa Sabakaki; Munabi, Ian Guyton; Castelnuovo, Barbara; Kaimal, Arvind; Kasozi, William; Kambugu, Andrew; Musoke, Philippa; Katabira, Elly
This study set out to determine the prevalence of low bone mass following long-term exposure to antiretroviral therapy in Ugandan people living with HIV.A cross-sectional study was conducted among 199 people living with HIV that had been on anti-retroviral therapy for at least 10 years. All participants had dual X-ray absorptiometry to determine their bone mineral density. The data collected included antiretroviral drug history and behavioral risk data Descriptive statistics were used to summarize the data. Inferential statistics were analyzed using multilevel binomial longitudinal Markov chain Monte Carlo mixed multivariate regression modelling using the rstanarm package.One hundred ninety nine adults were enrolled with equal representation of males and females. The mean age was 39.5 (SD 8.5) years. Mean durations on anti-retroviral treatment was 12.1 (SD 1.44) years, CD4 cell count was 563.9 cells/mm3. 178 (89.5%) had viral suppression with <50 viral copies/ml. There were 4 (2.0%) and 36 (18%) participants with low bone mass of the hip and lumbar spine respectively. Each unit increase in body mass index was associated with a significant reduction in the odds for low bone mineral density of the hip and lumbar spine. The duration on and exposure to the various antiretroviral medications had no significant effect on the participant’s odds for developing low bone mass. All the coefficients of the variables in a multivariable model for either hip or lumbar spine bone mass were not significant.These results provide additional evidence that patients on long term ART achieve bone mass stabilization. Maintaining adequate body weight is important in maintaining good bone health in people on antiretroviral therapy.
Low isoniazid and rifampicin concentrations in TB/HIV co-infected patients in Uganda
(Journal of the International AIDS Society, 2014) Sekaggya Wiltshire, Christine; Lamorde, Mohammed; Scherrer, Alexandra; Musaazi, Joseph; Corti, Natascia; Allan, Buzibye; Nakijoba, Rita; Nalwanga, Damalie; Henning, Lars; Von Braun, Amrei; Okware, Solome; Kambugu, Andrew; Fehr, Jan; Castelnuovo, Barbara
There is limited data available on exposure to anti-tuberculosis (TB) drugs in this region. Peloquin has described reference ranges [1] however some studies have demonstrated that patients actually achieve concentrations below these ranges [2]. There is limited data about exposure to anti-TB drugs in the HIV/TB co-infected population in Sub-Saharan Africa. Our objective is to describe the concentration of anti-TB drug levels in a well characterized prospective cohort of adult patients starting treatment for pulmonary TB. Methods: This study is an ongoing study carried out in the TB/HIV integrated clinic at the Infectious Diseases Institute in Kampala, Uganda. Sputum culture and microscopy was done for all patients. We performed pharmacokinetic blood sampling of anti-TB drugs for 1 hour, 2 hours and 4 hours post dose at 2 weeks, 8 weeks and 24 weeks after initiation of anti-TB treatment using ultraviolet high-performance liquid chromatography (UV-HPLC). We described the maximum concentration (Cmax) of isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) and compare them with the values observed by Peloquin et al. referenced in other studies. Results: We started 113 HIV infected adults on a fixed dose combination of HREZ. The median age of our population was 33 years, of which 52% were male with a median BMI of 19 kg/m2 and a median CD4 cell count of 142 cells/mL. In 90% of the participants, the diagnosis of TB was based on microscopy and or cultures. The boxplot graph shows the median Cmax and IQR of H and R. Levels of H were found to be below the reference ranges (3 6 mg/mL) in 54/77(70.1%), 38/59(64.4%) and 15/24(62.5%) participants at weeks 2, 8 and 24. Rif levels were also found to be below the reference ranges (8 24 mg/mL) in 41/66(62.1%), 26/48(54.2%) and 8/10(8%) participants at weeks 2, 8 and 24, respectively. The mean Cmax of E and Z were within the reference range at week 2 and 8; mean Cmax of 3.29SD2.1 mg/mL and 4.09SD3.1 mg/mL for E and 41.69SD13.1 mg/mL and 42.69SD16.4 mg/mL for Z. Conclusion: We observed lower concentrations of isoniazid and rifampicin in our study population of HIV/TB co-infected patients. The implications of these findings are not yet clear.We therefore need to correlate our findings with the response to TB treatment.
Patient and health system factors associated with pretreatment loss to follow up among patients diagnosed with tuberculosis using Xpert® MTB/RIF testing in Uganda
(BMC public health, 2020) Zawedde-Muyanja, Stella; Katamba, Achilles; Cattamanchi, Adithya; Castelnuovo, Barbara; Manabe, Yukari C.
In 2018, Uganda started only 65% of persons with incident tuberculosis on treatment. Pretreatment loss to follow up is an important contributor to suboptimal treatment coverage. We aimed to describe the patient and health facility-level characteristics associated with pretreatment loss to follow up among patients diagnosed with pulmonary tuberculosis at public health facilities in Uganda. Methods: At ten public health facilities, laboratory register data was used to identify patients aged ≥ 15 years who had a positive Xpert®MTB/RIF test. Initiation on TB treatment was ascertained using the clinical register. Factors associated with not being initiated on TB treatment within two weeks of diagnosis were examined using a multilevel logistic regression model accounting for clustering by health facility. Results: From January to June 2018, 510 patients (61.2% male and 31.5% HIV co-infected) were diagnosed with tuberculosis. One hundred (19.6%) were not initiated on TB treatment within 2 weeks of diagnosis. Not having a phone number recorded in the clinic registers (aOR 7.93, 95%CI 3.93–13.05); being HIV-infected (aOR 1.83; 95% CI: 1.09–3.26) and receiving care from a high volume health facility performing more than 12 Xpert tests per day (aOR 4.37, 95%CI 1.69–11.29) and were significantly associated with pretreatment loss to follow up. Conclusion: In public health facilities in Uganda, we found a high rate of pretreatment loss to follow up especially among TBHIV co-infected patients diagnosed at high volume health facilities. Interventions to improve the efficiency of Xpert® MTB/RIF testing, including monitoring of the TB care cascade should be developed and implemented.

Browsing by Author "Castelnuovo, Barbara"

Results Per Page

Sort Options