The East Africa Consortium for human papillomavirus and cervical cancer in women living with HIV/AIDS.

The East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer, and to encourage collaborations between researchers in North America and East African countries. To date, studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on the persistence of HPV, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP. It will now be determined how HPV testing fits into cervical cancer screening programs in Kenya and Uganda, how aflatoxin influences immunological control of HIV, how HPV alters certain genes involved in the growth of tumours in HIV-infected women. Although there have been challenges in performing this research, with time, this work should help to reduce the burden of cervical cancer and other cancers related to HIV infection in people living in sub-Saharan Africa, as well as optimized processes to better facilitate research as well as patient autonomy and safety. KEY MESSAGESThe East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer.Collaborations have been established between researchers in North America and East African countries for these studies.Studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on HPV detection, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP.

Reasons for first line ART modification over the years during the ART scale up in Uganda.

BACKGROUND: During the initial scale up of ART in sub-Saharan Africa, prescribed regimens included drugs with high potential for toxicity (particularly stavudine). More recently a growing number of patients requires second line treatment due to treatment failure, especially following the expansion of viral load testing. We aim to determine the reasons and risk factors for modification of first line ART across the years. METHODS: We included patients started on standard first line ART (2NRTI + 1 NNRTI) between 2005 and 2016 at the Infectious Diseases Institute, Kampala, Uganda. We described the reasons for treatment modification categorized in (1) toxicity (2) treatment failure (3) other reason (new TB treatment, new pregnancy). We used Cox proportional hazard to identify factors associated with treatment modification due to toxicity. RESULTS: We included 14,261 patients; 9114 (63.9%), were female, the median age was 34 years (IQR: 29-40), 60.8% were in WHO stage 3 and 4. The median BMI and CD4 count were 21.9 (IQR: 19.6-24.8) and 188 cell/µL (IQR: 65-353) respectively; 27.5% were started on stavudine, 46% on zidovudine, and 26.5% on a tenofovir containing regimens. We observed 6248 ART modifications in 4868/14,261 patients (34.1%); 1615 were due to toxicity, 1077 to treatment failure, 1330 to contraindications, and 1860 patients following WHO recommendation of phasing out stavudine and substituting with another NRTI. Modification for drug toxicity declined rapidly after the phase out of stavudine (2008), while switches to second line regimes increased after the implementation of viral load monitoring (2015). Patients with normal BMI compared to underweight, (HR: 0.79, CI 0.69-0.91), with CD4 counts 200-350 cells/µL compared to < 200 cells/µL (HR: 0.81- CI 0.71-0.93), and started on zidovudine (HR: 0.51 CI 0.44-0.59) and tenofovir (HR: 0.16, CI 0.14-0.22) compared to stavudine were less likely to have ART modification due to toxicity. Older patients (HR: 1.14 per 5-year increase CI 1.11-1.18), those in WHO stage 3 and 4 (HR: 1.19, CI 1.06-1.34) were more likely to have ART modification due to toxicity. CONCLUSIONS: Toxicity as reason for drugs substitution decreased over time mirroring the phase out of stavudine, while viral load expansion identified more patients in need of second line treatment.

Sustained positive impact on tuberculosis treatment outcomes of TB-HIV integrated care in Uganda.

To examine tuberculosis (TB) treatment outcomes from a long-term TB-HIV (human immunodeficiency virus) integrated model of care at the Infectious Diseases Institute Clinic, Kampala, Uganda. We included HIV-positive adults who were new TB cases initiated on anti-tuberculosis treatment between 2009 and 2015 during TB-HIV integration. Trends in TB treatment outcomes and TB-associated deaths were analyzed using respectively the χ² trend test and Kaplan-Meier methods. The analysis involved 1318 cases: most patients were female (>50%); the median age ranged from 34 to 36 years, and >60% were late presenters (CD4 count <200 cells/µl), with a median CD4 cell count of 100-146 cells/µl at TB diagnosis. TB treatment success (cured or treatment completed) was 67-76%. Loss to follow-up (LTFU) declined systematically from 7% in 2010 to 3.4% in 2015 (P < 0.01). Antiretroviral therapy (ART) initiation during the intensive phase improved from 47% in 2009 to 97% in 2015 (P < 0.01). The mortality rate was >15% over time, and the probability of death at month 2 of anti-tuberculosis treatment was 52% higher among late presenters than in early presenters (13% vs. 6%, P < 0.01). Significant LTFU improvement and prompt ART initiation could be due to well-implemented TB-HIV integration care; however, static TB-associated deaths may be due to late presentation. .

Tuberculosis treatment success among rural and urban Ugandans living with HIV: a retrospective study.

Setting: Government health centres and hospitals (six urban and 20 rural) providing tuberculosis (TB) treatment for people living with the human immunodeficiency virus (PLHIV) in central and western Uganda. Objective: To identify and quantify modifiable factors that limit TB treatment success among PLHIV in rural Uganda. Design: A retrospective cross-sectional review of routine Uganda National Tuberculosis and Leprosy Programme clinic registers and patient files of HIV-positive patients who received anti-tuberculosis treatment in 2014. Results: Of 191 rural patients, 66.7% achieved treatment success compared to 81.1% of 213 urban patients. Adjusted analysis revealed higher average treatment success in urban patients than in rural patients (OR 3.95, 95%CI 2.70-5.78, P < 0.01, generalised estimating equation model). Loss to follow-up was higher and follow-up sputum smear results were less frequently recorded in TB clinic registers among rural patients. Patients receiving treatment at higher-level facilities in rural settings had greater odds of treatment success, while patients receiving treatment at facilities where drug stock-outs had occurred had lower odds of treatment success. Conclusion: Lower reported treatment success in rural settings is mainly attributed to clinic-centred factors such as treatment monitoring procedures. We recommend strengthening treatment monitoring and delivery.

Contexte: L'étude a été réalisée dans des centres de santé et des hôpitaux publics, six urbains et 20 ruraux, fournissant un traitement de la tuberculose (TB) aux personnes vivant avec le VIH (PVVIH) dans le centre et l'ouest de l'Ouganda.Objectif: Identifier et quantifier les facteurs modifiables qui limitent le succès du traitement de la TB parmi les PVVIH dans l'Ouganda rural.Schéma: Une revue rétrospective transversale des registres cliniques et des dossiers de patients du Programme national tuberculose et lèpre d'Ouganda pour les patients VIH positifs qui ont reçu un traitement de TB en 2014.Résultats: Parmi 191 patients ruraux, 66,7% ont eu un bon résultat de leur traitement, tandis que parmi 213 patients urbains, 81,1% ont eu un bon résultat. Une analyse ajustée a révélé un succès thérapeutique moyen plus élevé chez les patients urbains comparés aux patients ruraux (OR 3,95 ; IC95% 2,70­5,78 ; P < 0,01 ; modèle d'équation d'estimation généralisée). Les pertes de vue ont été plus élevées et les résultats de frottis de crachats de suivi ont été moins souvent enregistrés dans les registres des centres TB pour les patients ruraux. Les patients recevant un traitement dans des structures de plus haut niveau, toujours en zone rurale, avaient plus de chances d'avoir un succès thérapeutique. Les patients recevant leur traitement dans des structures où étaient survenues des ruptures de stock de médicaments avaient moins de chances de succès thérapeutique.Conclusion: Les taux plus faibles de succès du traitement rapportés en zone rurale sont en majorité attribués à des facteurs liés aux centres de santé, comme les procédures de suivi du traitement. Nous recommandons le renforcement de la fourniture et du suivi du traitement.

Marco de referencia: El estudio se llevó a cabo en centros de salud y hospitales del sector público, seis en entornos urbanos y 20 en medio rural y consistió en suministrar el tratamiento antituberculoso a las personas positivas frente al virus de la inmunodeficiencia humana (VIH) en la región central y occidental de Uganda.Objetivo: Determinar y cuantificar los factores modificables que limitan la eficacia del tratamiento antituberculoso en las personas positivas frente al VIH en las zonas rurales de Uganda.Método: Fue este un estudio transversal retrospectivo de análisis de los registros corrientes y las historias clínicas de los pacientes positivos frente al VIH, en los consultorios del Programa Nacional contra la Tuberculosis y la Lepra de Uganda en el 2014.Resultados: De los 191 pacientes de entornos rurales, el 66,7% logró un tratamiento eficaz y en los 213 pacientes en medio urbano esta proporción fue 81,1%. Un análisis ajustado reveló un promedio de éxito terapéutico más alto en los pacientes urbanos en comparación con los pacientes rurales (OR 3,95; IC95% de 2,70 a 5,78; P < 0,01, según un modelo de ecuaciones de estimación generalizadas). En medio rural, se observó una mayor pérdida durante el seguimiento y se consignaban con menor frecuencia los resultados de las baciloscopias de seguimiento en los registros de tuberculosis de los consultorios. Los pacientes que recibían tratamiento en los establecimientos de nivel de atención más alto en medio rural tenían mayores posibilidades de éxito terapéutico. Los pacientes que recibían tratamiento en centros que presentaban desabastecimientos de medicamentos tuvieron menos probabilidades de lograr un tratamiento eficaz.Conclusión: La menor proporción de éxito terapéutico notificada en los entornos rurales se debe en su mayor parte a factores que dependen del consultorio, como los procedimientos de supervisión del tratamiento. Se recomienda reforzar la supervisión y el suministro del tratamiento antituberculoso.

Factors before enrolment are associated with being removed from a Pharmacy-only Refill Programme at a large urban HIV/AIDS clinic, Uganda.

A Pharmacy-only Refill Programme (PRP) a type of task shifting in which stable HIV-positive patients are managed through pharmacy-only visits instead of physician visits. We performed a study to identify factors for being removed from the PRP in order to establish better referral criteria. The study was performed at the Infectious Disease Clinic (IDC) in Kampala, Uganda. We selected a random sample of 588 patients from 2431 patients on antiretroviral therapy referred to the PRP at least 12 months before commencement of the PRP evaluation. We compared the characteristics of patients who during 12 months of follow-up were removed from the PRP with those who continued to be followed up. Data were abstracted from the IDC data base, the pharmacy register and the patient clinical notes. Of 588 patients, 106 (18%) were removed from the PRP. In multivariate analysis, less than 100% self-reported adherence to antiretroviral therapy, missing at least one scheduled appointment in the six months before referral to the PRP and being on a lopinavir/ritonavir-containing regimen were independently associated with being removed from the PRP. Criteria for referring patients to a PRP should focus on antiretroviral therapy adherence and appointment keeping. Patients on a lopinavir/ritonavir-containing regimen should not be targeted for a PRP. On the other hand a PRP is an efficient strategy that targets stable adherent patients in clinics with high patient load.

Low frequency of liver enzyme elevation in HIV-infected patients attending a large urban treatment centre in Uganda.

Liver enzyme elevations among patients on antiretroviral therapy (ART) were determined by prospectively evaluating aspartate aminotransferase (AST) data in a cohort of patients in Kampala over 36 months. A proportion of patients had hepatitis B virus (HBV) status determined. Hepatotoxicity was graded I to IV according to the AIDS Clinical Trial Group criteria. Of 546 patients, 377 (69%) were women; overall median baseline CD4+ T-cell was 97/µL (interquartile range [IQR] 20-164). Hepatitis B surface antigen (HBsAg) was detected in 42 (9%) of 470 persons. ART included lamivudine, with either nevirapine and d4T (74%) or efavirenz and AZT (26%). Median (IQR) AST level at baseline was 35 (27, 53 IU/L). Over 36 months, only eight patients had grade III AST elevation. Neither HBsAg nor ART regimen influenced AST levels. Male gender and CD4+ change from baseline were correlated with AST elevation. Patients with HIV/HBV co-infection were not at an increased risk of AST elevation, which occurred uncommonly in this setting.