Browsing by Author "Kambugu, Andrew"
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Item 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, BarbaraSeveral 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.Item 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 ParksLittle 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.Item Baseline Xpert MTB/RIF ct values predict sputum conversion during the intensive phase of anti-TB treatment in HIV infected patients in Kampala, Uganda: a retrospective study(BMC Infectious Diseases, 2021) Namugenyi, Juliet; Musaazi, Joseph; Katamba, Achilles; Kalyango, Joan; Sendaula, Emmanuel; Kambugu, Andrew; Fehr, Jan; Castelnouvo, Barbara; Manabe, Yukari C.; Ssengooba, Willy; Sekaggya-Wiltshire, ChristineIn resource-limited settings, sputum smear conversion is used to document treatment response. Many People living with HIV (PLHIV) are smear-negative at baseline. The Xpert MTB/RIF test can indirectly measure bacterial load through cycle threshold (ct) values. This study aimed to determine if baseline Xpert MTB/RIF could predict time to culture negativity in PLHIV with newly diagnosed TB. Methods: A subset of 138 PLHIV from the ‘SOUTH’ study on outcomes related to TB and antiretroviral drug concentrations were included. Bacterial load was estimated by Mycobacterium Growth Indicator Tubes (MGIT) culture time-to-positivity (TTP) and Lowenstein Jensen (LJ) colony counts. Changes in TTP and colony counts were analyzed with Poisson Generalised Estimating Equations (GEE) and multilevel ordered logistic regression models, respectively, while time to culture negativity analysed with Cox proportional hazard models. ROC curves were used to explore the accuracy of the ct value in predicting culture negativity. Results: A total of 81 patients (58.7%) were males, median age 34 (IQR 29 ̶ 40) years, median CD4 cell count of 180 (IQR 68 ̶345) cells/μL and 77.5% were ART naive. The median baseline ct value was 25.1 (IQR 21.0 ̶ 30.1). A unit Increase in the ct value was associated with a 5% (IRR = 1.05 95% CI 1.04 ̶ 1.06) and 3% (IRR = 1.03 95% CI 1.03 ̶ 1.04) increase in TTP at week 2 and 4 respectively. With LJ culture, a patient’s colony grade was reduced by 0.86 times (0R = 0.86 95% CI 0.74 ̶ 0.97) at week 2 and 0.84 times (OR = 0.84 95% CI 0.79 ̶ 0.95 P = 0.002) at week 4 for every unit increase in the baseline ct value. There was a 3% higher likelihood of earlier conversion to negativity for every unit increase in the ct value. A ct cut point ≥28 best predicted culture negativity at week 4 with a sensitivity of 91. 7% & specificity 53.7% while a cut point ≥23 best predicted culture negativity at week 8. Conclusion: Baseline Xpert MTB/RIF ct values predict sputum conversion in PLHIV on anti-TB treatment. Surrogate biomarkers for sputum conversion in PLHIV are still a research priority.Item Basis of selection of first and second line highly active antiretroviral therapy for hiv/aids on genetic barrier to resistance: a literature review.(African Health Sciences, 2014) Katusiime, Christine; Ocama, Ponsiano; Kambugu, AndrewThe effectiveness of combination antiretroviral therapy (cART) continues to improve as treatment choices expand with the development of new antiretroviral agents and regimens. However, the successful long-term treatment of HIV/AIDS is under threat from the emergence of drug-resistant strains to multiple agents and entire drug classes.Item 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, ConceptaResearch 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.Item A Case of Palatal Perforation Caused by Toxoplasmosis(Southern African Journal of HIV Medicine, 2010) Katusiime, Christine; Ocama, Ponsiano; Kambugu, AndrewHIV infection has several oral manifestations, including oral candidiasis and oral hairy leucoplakia. Occasionally unusual presentations requiring rigorous investigations are seen, and in these cases the diagnosis sometimes remains a dilemma owing to limited investigation facilities.1-3 We present the case of a patient who presented with a puzzling oral lesion.Item Closing the Gap Toward Zero Tetanus Infection for Voluntary Medical Male Circumcision: Seven Case Reports and a Review of the Literature(Surgical Infections, 2020) Galukande, Moses; Were, Leonard F.; Kigozi, Joanita; Kahendeke, Carol; Muganzi, Alex; Kambugu, AndrewVoluntary medical male circumcision (VMMC) is important for HIV prevention, providing up to 60% protection. Although VMMC is usually a safe procedure, it is not free of associated serious adverse events. In the Uganda VMMC program, which is available to males 10 years of age and older, 11 individuals were reported with tetanus infection out of almost 3.5 million circumcisions over an eight-year period (2009–2018). The majority had received tetanus vaccination prior to VMMC. Disproportionately and statistically significantly, the elastic collar compression method accounted for half the tetanus infection cases, despite contributing to only less than 10% of circumcisions done. This article describes gaps in presumed tetanus vaccination (TTV) protection along with relevant discussions and recommendations. Case Presentations: We present seven tetanus case reports and a review of the literature. We were guided by a pre-determined thematic approach, focusing on immune response to TTV in the context of common infections and infestations in a tropical environment that may impair immune response to TTV. It is apparent in the available literature that the following (mostly tropical neglected infections) sufficiently impair antibody response to TTV: human immunodefiency virus (HIV), pulmonary tuberculosis, nematode infections, and schistosomiasis. Conclusions: One of seven patients died (14% case fatality). Individuals with prior exposure to certain infection( s) may not mount adequate antibody response to TTV sufficient to protect against acquiring tetanus. Therefore, TTV may not confer absolute protection against tetanus infection in these individuals. More needs to be done to ensure everyone is fully protected against tetanus, especially in the regions where risk of tetanus is heightened. We need to characterize the high-risk individuals (poor responders to TTV) and design targeted protective measures.Item 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, AndrewTuberculosis (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.Item 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.Item Development and Evaluation of a Clinical Algorithm to Monitor Patients on Antiretrovirals in Resource-Limited Settings using Adherence, Clinical and CD4 Cell Count Criteria(Journal of the International AIDS Society, 2009) Meya, David; Spacek, Lisa A.; Tibenderana, Hilda; John, Laurence; Namugga, Irene; Magero, Stephen; Dewar, Robin; Quinn, Thomas C.; Colebunders, Robert; Kambugu, Andrew; Reynol, Steven J.Routine viral load monitoring of patients on antiretroviral therapy (ART) is not affordable in most resource-limited settings.A cross-sectional study of 496 Ugandans established on ART was performed at the Infectious Diseases Institute, Kampala, Uganda. Adherence, clinical and laboratory parameters were assessed for their relationship with viral failure by multivariate logistic regression. A clinical algorithm using targeted viral load testing was constructed to identify patients for second-line ART. This algorithm was compared with the World Health Organization (WHO) guidelines, which use clinical and immunological criteria to identify failure in the absence of viral load testing.Forty-nine (10%) had a viral load of >400 copies/mL and 39 (8%) had a viral load of >1000 copies/mL. An algorithm combining adherence failure (interruption >2 days) and CD4 failure (30% fall from peak) had a sensitivity of 67% for a viral load of >1000 copies/mL, a specificity of 82%, and identified 22% of patients for viral load testing. Sensitivity of the WHO-based algorithm was 31%, specificity was 87%, and would result in 14% of those with viral suppression (<400 copies/mL) being switched inappropriately to second-line ART.Algorithms using adherence, clinical and CD4 criteria may better allocate viral load testing, reduce the number of patients continued on failing ART, and limit the development of resistance.Item Efficacy and Safety of Dolutegravir or Darunavir in Combination with Lamivudine plus either Zidovudine or Tenofovir for second-line Treatment of HIV Infection (NADIA): week 96 results from a Prospective, Multicentre, Open-label, Factorial, Randomised, Non-inferiority trial(The Lancet HIV, 2022) Paton, Nicholas I.; Musaazi, Joseph; Kityo, Cissy; Walimbwa, Stephen; Hoppe, Anne; Balyegisawa, Apolo; Mirembe, Grace; Lugemwa, Abbas; Ategeka, Gilbert; Mugerwa, Henry; Kambugu, AndrewWHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine. In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete.Item 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.Item Evaluation of Trypan Blue Stain in a Haemocytometer for Rapid Detection of Cerebrospinal Fluid Sterility in HIV Patients with Cryptococcal Meningitis(BMC microbiology, 2017) Kwizera, Richard; Akampurira, Andrew; Kandole, Tadeo K.; Kambugu, Andrew; Kambugu, Andrew; Meya, David B.; Boulware, David R.; Rhein, Joshua; on behalf of the ASTRO-CM Study TeamQuantitative culture is the most common method to determine the fungal burden and sterility of cerebrospinal fluid (CSF) among persons with cryptococcal meningitis. A major drawback of cultures is a long turnaround-time. Recent evidence demonstrates that live and dead Cryptococcus yeasts can be distinguished using trypan blue staining. We hypothesized that trypan blue staining combined with haemocytometer counting may provide a rapid estimation of quantitative culture count and detection of CSF sterility. To test this, we evaluated 194 CSF specimens from 96 HIV-infected participants with cryptococcal meningitis in Kampala, Uganda. Cryptococcal meningitis was diagnosed by CSF cryptococcal antigen (CRAG). We stained CSF with trypan blue and quantified yeasts using a haemocytometer. We compared the haemocytometer readings versus quantitative Cryptococcus CSF cultures. Haemocytometer counting with trypan blue staining had a sensitivity of 98% (64/65), while CSF cultures had a sensitivity of 95% (62/65) with reference to CSF CRAG for diagnostic CSF specimens. For samples that were positive in both tests, the haemocytometer had higher readings compared to culture. For diagnostic specimens, the median of log10 transformed counts were 5.59 (n = 64, IQR = 5.09 to 6.05) for haemocytometer and 4.98 (n = 62, IQR = 3.75 to 5.79) for culture; while the overall median counts were 5.35 (n = 189, IQR = 4.78–5.84) for haemocytometer and 3.99 (n = 151, IQR = 2.59–5.14) for cultures. The percentage agreement with culture sterility was 2.4% (1/42). Counts among non-sterile follow-up specimens had a median of 5.38 (n = 86, IQR = 4.74 to 6.03) for haemocytometer and 2.89 (n = 89, IQR = 2.11 to 4.38) for culture. At diagnosis, CSF quantitative cultures correlated with haemocytometer counts (R2 = 0.59, P < 0.001). At 7–14 days, quantitative cultures did not correlate with haemocytometer counts (R2 = 0.43, P = 0.4). Despite a positive correlation, the haemocytometer counts with trypan blue staining did not predict the outcome of quantitative cultures in patients receiving antifungal therapy.Item Feasibility of Virtual Reality based Training for Optimizing COVID-19 Case Handling in Uganda(Research square, 2021) Buyego, Paul; Katwesigye, Elizabeth; Nsubuga, Mike; Nakyejwe, Shirley; Cruz, Phillip Cruz; McCarthy, Meghan; Hurt, Darrell; Kambugu, Andrew; Arinaitwe, Joseph Walter; Umaru, Ssekabira; Daudi, JjingoEpidemics and pandemics are causing high morbidity and mortality on a still-evolving scale exemplified by the COVID-19 pandemic. Infection prevention and control (IPC) training for frontline health workers is thus essential. However, classroom or hospital ward based training portends an infection risk due to the in-person interaction of participants. We explored the use of Virtual Reality (VR) simulations for frontline health worker training since it trains participants without exposing them to infections that would arise from in-person training. It does away with the requirement for expensive Personal Protective Equipment (PPE) that has been in acute shortage and improves learning, retention and recall. This represents the first attempt in deploying VR-based pedagogy in a Ugandan medical education context.Item Gastrointestinal cryptococcoma – Immune reconstitution inflammatory syndrome or cryptococcal relapse in a patient with AIDS?(Medical mycology case reports, 2015) Musubire, Abdu K.; Meya, David B.; Lukande, Robert; Kambugu, Andrew; Bohjanen, Paul R.; Boulware, David R.The introduction of antiretroviral therapy (ART) may lead to unusual paradoxical and unmasking pre- sentations of opportunistic infections. Intra-abdominal cryptococcosis is a rare manifestation of Cryp- tococcus. We present the case of an HIV-infected patient on ART, with a history of cryptococcal meningitis who presented with subacute, worsening abdominal pain during immune recovery. This evolved into chronic abdominal pain, with thickened bowel, and abdominal lymphadenopathy, while receiving em- piric tuberculosis treatment. At 6-months, he developed intestinal perforation due to a histologically confirmed cryptococcoma.Item Health Worker Perspectives on Barriers and Facilitators of Assisted Partner Notification for HIV for Refugees and Ugandan Nationals: A Mixed Methods Study in West Nile Uganda(AIDS and Behavior, 2021) Klabbers, Robin E.; Muwonge, Timothy R.; Ayikobua, Emmanuel; Izizinga, Diego; Bassett, Ingrid V.; Kambugu, Andrew; Tsai, Alexander C.; Ravicz, Miranda; Klabbers, Gonnie; O’Laughlin, Kelli N.Assisted partner notification (APN) is recommended by the World Health Organization to notify sexual partners of HIV exposure. Since 2018, APN has been offered in Uganda to Ugandan nationals and refugees. Distinct challenges faced by individuals in refugee settlements may influence APN utilization and effectiveness. To explore APN barriers and facilitators, we extracted index client and sexual partner data from APN registers at 11 health centers providing care to refugees and Ugandan nationals in West Nile Uganda and conducted qualitative interviews with health workers (N = 32). Since APN started, 882 index clients participated in APN identifying 1126 sexual partners. Following notification, 95% (1025/1126) of partners tested for HIV; 22% (230/1025) were diagnosed with HIV with 14% (139/1025) of tested partners newly diagnosed. Fear of stigma and disclosure-related violence limit APN utilization and effectiveness. Prospective research involving index clients and sexual partners is needed to facilitate safe APN optimization in refugee settlements.Item 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, ChristineTo 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.Item HIV serostatus disclosure and lived experiences of adolescents at the Transition Clinic of the Infectious Diseases Clinic in Kampala, Uganda: A qualitative study(Routledge, 2012) Siu, Godfrey E.; Bakeera-kitaka, Sabrina; Kennedy, Caitlin E.; Dhabangi, Aggrey; Kambugu, AndrewMost studies on HIV serostatus disclosure and adolescents focus on whether, how and when to disclose to adolescents their HIV diagnosis. Fewer studies have examined HIV serostatus disclosure by adolescents who know they are infected with HIV. This study presents qualitative data examining HIV serostatus and treatment disclosure practices and concerns of young people living with HIV in Uganda and the extent to which they are satisfied with current norms around HIV serostatus and treatment disclosure. We conducted two focus groups and interviewed 20 HIV-infected young people aged 15 23 receiving HIV care and treatment at the Transition Clinic in Kampala. Respondents perceived disclosure as a relationship encompassing both communication and self-conduct. Adolescents employed unique strategies to disclose their HIV status, notably joking to ‘‘test the waters’’ and emotionally prepare the other person before later disclosing in a more serious manner. Findings reinforce the idea that HIV disclosure is a process, not a one-time event. Interviewees anticipated both positive and negative outcomes of disclosure, including financial and emotional support, stigma, discrimination and rejection. They described a sense of violation of their autonomy when confidentiality was breached by third party disclosure, and also expressed fear of emotional distress for their loved ones. Although adolescents yearned to be in control of information about their HIV status and treatment, they have little space to call their own, and privacy is often compromised, especially because in traditional African settings, young people are considered to be dependents under the full responsibility of caregivers. Further exploration of disclosure outcomes and strategies specific to adolescents can help better tailor interventions towards youth. Antiretroviral therapy programmes should consider counselling for caretakers to appreciate and respect the privacy and disclosure concerns of their HIV-infected children.Item Immune Reconstitution Inflammatory Syndrome among Adolescents: A Report of Cases in a Resource-Limited Setting (Uganda)(Southern African Journal of HIV Medicine, 2010) Katusiime, Christine; Ocama, Ponsiano; Kambugu, AndrewThe immune reconstitution inflammatory syndrome (IRIS) is a frequent early complication of antiretroviral therapy (ART), particularly in patients who commence ART with low CD4 counts and established opportunistic infections. IRIS in HIV-infected patients results from a pathological inflammatory response to pre-existing infective, host or other antigens, alive or dead, causing clinical deterioration after initiating ART.1 The most common forms of IRIS occur in association with mycobacterial and herpesvirus infections. Adolescents and young adults comprise an increasing proportion of new HIV infections both in developing and developed countries, and little is known regarding HIV IRIS in this group. As the ART roll-out has gathered pace since 2004 in resource-limited settings, adolescent IRIS has emerged as a clinical challenge. We describe adolescent/young adult patients who presented to our clinic with IRIS events.Item 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, AndrewStarting 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.