Patient and healthcare provider experiences of hepatitis C treatment with direct-acting antivirals in Rwanda: a qualitative exploration of barriers and facilitators.

BACKGROUND: Direct-acting antivirals (DAAs) are increasingly accessible to patients with hepatitis C (HCV) worldwide and are being introduced through national health systems in sub-Saharan Africa. DAAs are highly efficacious when tested in controlled trials, yet patients treated outside of study settings often encounter challenges in completing the full treatment and follow-up sequence. Little information is available on the influences of successful DAA implementation in sub-Saharan Africa. This qualitative study explored the individual- and system-level barriers and enablers of DAA treatment in Rwanda between March 2015 and November 2017. METHODS: Face-to-face interviews were conducted with 39 patients who initiated care at one of four referral hospitals initially offering DAAs. Ten healthcare providers who managed HCV treatment participated in face-to-face interviews to examine system-level barriers and facilitators. Interview data were analyzed using a general inductive approach in alignment with the a priori objective of identifying barriers and facilitators of HCV care. RESULTS: Barriers to successful treatment included patients' lack of knowledge surrounding HCV and its treatment; financial burdens associated with paying for medication, laboratory testing, and transportation; the cumbersome nature of the care pathway; the relative inaccessibility of diagnostics technology; and heavy workloads of healthcare providers accompanied by a need for additional HCV-specific training. Patients and healthcare providers were highly aligned on individual- and system-level barriers to care. The positive patient-provider relationship, strong support from community and family members, lack of stigma, and mild side effect profile of DAAs all positively influenced patients' engagement in treatment. CONCLUSIONS: Several interrelated factors acted as barriers and facilitators to DAA treatment in Rwanda. Patients' and healthcare providers' perceptions were in agreement, suggesting that the impeding and enabling factors were well understood by both groups. These results can be used to enact evidence-informed interventions to help maximize the impact of DAAs as Rwanda moves towards HCV elimination.

Viral load detection and management on first line ART in rural Rwanda.

BACKGROUND: To achieve the ambitious 90-90-90 UNAIDS targets, access to routine viral load (VL) is critical. To measure VL, Rwanda has relied on a national reference laboratory for years. In 2014, a VL testing platform was implemented in a rural District in the Northern Province. Here we analyze the uptake of VL testing, identification of risks for detectable VL (≥1000 copies/ml), and the management of patients with a detectable VL. METHODS: A retrospective cohort study of patients who started ART between July 2012 and June 2015 and followed until end December 2016. Using descriptive statistics, we describe the VL cascade, from VL uptake to the start of second-line ART in patients diagnosed with virological failure. We estimate predictors of having a detectable VL using logistic regression. RESULTS: The uptake of VL testing increased progressively between 2013 and 2016, raising from 25.6% (39/152) in 2013 up to 93.2% (510/547) in 2016.In 2016, 88.5% (n = 451) of patients tested, had a suppressed VL. Predictors of having a detectable VL included being male (aOR 2.1; 95%CI 1.12-4.02; p = 0.02), being a sex worker (aOR 6.4; 95%CI 1.1-36.0; p = 0.04), having a WHO clinical stage IV when starting ART (aOR 8.8; 95%CI 1.8-43.0; p < 0.001), having had a previous detectable VL (aOR 7.2; 95%CI 3.5-14.5; p < 0.001), and having had no VL before 2016 (aOR 3.1; 95%CI 1.2-8.1; p = 0.02). Among patients with initial detectable VL between 2013 and 2016, 88% (n = 103) had a follow-up VL, of whom 60.2% (n = 62) suppressed their VL below 1000 copies/ml. The median time between the initial and follow-up VL was of 12.5 months (IQR: 8.7-19.0). Among patients with confirmed treatment failure, 63.4% (n = 26) started second-line ART within the study period. CONCLUSION: VL uptake increased after decentralizing VL testing in rural Rwanda. Virological suppression was high. An individualized follow up of patients at risk of non-suppression and a prompt management of patients with detectable VL may help to achieve and sustain the third global UNAIDS target: virological suppression in 90% of patients on ART.

Implementation of a unique hepatitis C care continuum model in Rwanda.

BACKGROUND: There has been an evolution in the treatment of chronic hepatitis C (HCV) due to highly effective direct-acting antivirals, however, restriction of treatment to medical specialists hinders escalation of HCV treatment. This is particularly true in resource-limited settings (RLS), which disproportionately represent the burden of HCV worldwide. The ASCEND study in Washington, DC, demonstrated that complete task-shifting can safely and effectively overcome a low provider-to-patient ratio and expand HCV treatment. However, this model has not been applied internationally to RLS. METHOD: The validated ASCEND model was translated to an international clinical program in Kigali, Rwanda, aimed at training general medicine providers on HCV management and obtaining HCV prevalence data. RESULTS: The didactic training program administered to 11 new HCV providers in Rwanda increased provider's knowledge about HCV management. Through the training program, 26% of patients seen during the follow-up period were screened for HCV and a prevalence estimate of 2% was ascertained. Of these patients, 30% were co-infected with hepatitis B. CONCLUSION: The ASCEND paradigm can be successfully implemented in RLS to escalate HCV care, in a self-sustaining fashion that educates more providers about HCV management, while increasing the public's awareness of HCV and access to treatment.

Novel open-source electronic medical records system for palliative care in low-resource settings.

BACKGROUND: The need for palliative care in sub-Saharan Africa is staggering: this region shoulders over 67% of the global burden of HIV/AIDS and cancer. However, provisions for these essential services remain limited and poorly integrated with national health systems in most nations. Moreover, the evidence base for palliative care in the region remains scarce. This study chronicles the development and evaluation of DataPall, an open-source electronic medical records system that can be used to track patients, manage data, and generate reports for palliative care providers in these settings.DataPall was developed using design criteria encompassing both functional and technical objectives articulated by hospital leaders and palliative care staff at a leading palliative care center in Malawi. The database can be used with computers that run Windows XP SP 2 or newer, and does not require an internet connection for use. Subsequent to its development and implementation in two hospitals, DataPall was tested among both trained and untrained hospital staff populations on the basis of its usability with comparison to existing paper records systems as well as on the speed at which users could perform basic database functions. Additionally, all participants evaluated this program on a standard system usability scale. RESULTS: In a study of health professionals in a Malawian hospital, DataPall enabled palliative care providers to find patients' appointments, on average, in less than half the time required to locate the same record in current paper records. Moreover, participants generated customizable reports documenting patient records and comprehensive reports on providers' activities with little training necessary. Participants affirmed this ease of use on the system usability scale. CONCLUSIONS: DataPall is a simple, effective electronic medical records system that can assist in developing an evidence base of clinical data for palliative care in low resource settings. The system is available at no cost, is specifically designed to chronicle care in the region, and is catered to meet the technical needs and user specifications of such facilities.

Prevalence of Glucose Metabolic Disorders and Associated Inflammatory Markers Among People Living with HIV in Sub-Saharan Africa.

Background: Glucose metabolic disorder (GMD) is closely related to inflammation among those living with HIV. However, there are extant studies regarding this phenomenon in sub-Saharan Africa (SSA) that bears the burden of HIV infection. Therefore, we assessed the associations between inflammation biomarkers and GMD on a cohort of HIV+ individuals in SSA. Methods: We conducted a cross sectional study at the largest (patient volume) HIV clinic in Tanzania from March to May 2018. Purposive sampling was used to identify 407 HIV+ patients on treatment. Data were collected using the World Health Organization (WHO) STEPwise approach for noncommunicable disease surveillance. Clinical and demographic variables were extracted from the medical chart. Fasting blood glucose and inflammatory markers [C-reactive protein (CRP), interleukin (IL)-6, IL-18, and soluble tumor necrosis factor receptor (sTNFR)-1, sTNFR-2] were measured. Bivariate and multivariate analysis was conducted to examine the association between the biomarkers and GMD. Results: GMD was present in 67.6% (n = 271). Among those with GMD, 44.5%, 38.4%, and 17.1% presented with impaired fasting glucose, impaired glucose tolerance, and diabetes mellitus, respectively. Being older (>55 years) and initiating smoking at an age >28 years was associated with GMD (P = 0.05). Engaging in moderate activity significantly reduced the risk of GMD (P = 0.04). Having a current CD4 count between 351 and 500 reduced the odds of GMD by 66.7% in comparison to clients with CD4 counts ≤350. Comparing the highest to the lowest quartile at the multivariate level, only CRP showed an independent significant association with GMD (adjusted odds ratio: 1.9; 95% confidence interval: 1.03-3.57). Despite a linear relationship, none of the other biomarkers showed a significant association with GMD. Conclusion: Our study shows that high CRP and low CD4 are important contributors to the prevalence of GMD. Even when controlling for confounding variables did not diminish the associations between GMD and CRP. These findings point to the importance of creating awareness, education, and screening for GMD in high-epidemic countries. More rigorous studies are needed to identify the manifestation of inflammation in HIV patients.

Acquired HIV drug resistance among adults living with HIV receiving first-line antiretroviral therapy in Rwanda: A cross-sectional nationally representative survey.

BACKGROUND: We assessed the prevalence of acquired HIV drug resistance (HIVDR) and associated factors among patients receiving first-line antiretroviral therapy (ART) in Rwanda. METHODS: This cross-sectional study included 702 patients receiving first-line ART for at least 6 months with last viral load (VL) results ≥1000 copies/mL. Blood plasma samples were subjected to VL testing; specimens with unsuppressed VL were genotyped to identify HIVDR-associated mutations. Data were analysed using STATA/SE. RESULTS: Median time on ART was 86.4 months (interquartile range [IQR], 44.8-130.2 months), and median CD4 count at ART initiation was 311 cells/mm3 (IQR, 197-484 cells/mm3). Of 414 (68.2%) samples with unsuppressed VL, 378 (88.3%) were genotyped. HIVDR included 347 (90.4%) non-nucleoside reverse transcriptase inhibitor- (NNRTI), 291 (75.5%) nucleoside reverse transcriptase inhibitor- (NRTI) and 13 (3.5%) protease inhibitor (PI) resistance-associated mutations. The most common HIVDR mutations were K65R (22.7%), M184V (15.4%) and D67N (9.8%) for NRTIs and K103N (34.4%) and Y181C/I/V/YC (7%) for NNRTIs. Independent predictors of acquired HIVDR included current ART regimen of zidovudine + lamivudine + nevirapine (adjusted odds ratio [aOR], 3.333 [95% confidence interval (CI): 1.022-10.870]; p = 0.046) for NRTI resistance and current ART regimen of tenofovir + emtricitabine + nevirapine (aOR, 0.148 [95% CI: 0.028-0.779]; p = 0.025), zidovudine + lamivudine + efavirenz (aOR, 0.105 [95% CI: 0.016-0.693]; p = 0.020) and zidovudine + lamivudine + nevirapine (aOR, 0.259 [95% CI: 0.084-0.793]; p = 0.019) for NNRTI resistance. History of ever switching ART regimen was associated with NRTI resistance (aOR, 2.53 [95% CI: 1.198-5.356]; p = 0.016) and NNRTI resistance (aOR, 3.23 [95% CI: 1.435-7.278], p = 0.005). CONCLUSION: The prevalence of acquired HIV drug resistance (HIVDR) was high among patient failing to re-suppress VL and was associated with current ART regimen and ever switching ART regimen. The findings of this study support the current WHO guidelines recommending that patients on an NNRTI-based regimen should be switched based on a single viral load test and suggests that national HIV VL monitoring of patients receiving ART has prevented long-term treatment failure that would result in the accumulation of TAMs and potential loss of efficacy of all NRTI used in second-line ART as the backbone in combination with either dolutegravir or boosted PIs.

"Waiting for DAAs": A retrospective chart review of patients with untreated hepatitis C in Rwanda.

BACKGROUND: Access to treatment for hepatitis C virus (HCV) in sub-Saharan Africa is extremely limited. With the advent of direct acting antivirals (DAAs), highly effective and easy-to-deliver oral regimens are now available on the global market. This study was conducted to understand the background and characteristics of a national cohort of patients with HCV infection enrolled in care and awaiting therapy with DAAs. METHODS AND FINDINGS: We conducted a retrospective chart review of all adult patients with confirmed HCV infection who were currently enrolled in care and treatment at the four existing hepatitis referral centers in Rwanda. Patient charts at these centers were reviewed, and routinely collected data were recorded and analyzed. Overall, 253 patients were identified; median age was 56 years (IQR: 43, 65), and 149 (58.9%) were female. Median viral load was 688,736 IU/ml and 96.7% were HCV genotype 4. As classified by FIB-4 score, 64.8% of the patients had moderate to severe fibrosis. Fibrosis stage was associated with age (OR 1.12, CI 1.09-1.17), but not with time since diagnosis, gender, treatment center, or type of insurance. There was a low frequency of documented co-morbid conditions, including hypertension, diabetes, HIV, and hepatitis B virus. CONCLUSIONS: Compared to an estimated 55,000 patients eligible for HCV treatment in Rwanda, this study identified only 253 patients currently diagnosed and engaged in care, highlighting an immense treatment gap in HCV, likely due to the lack of accessible and affordable screening, diagnostic, and treatment modalities. The patients that were enrolled in care had a disproportionately advanced fibrosis stage, possibly indicating late presentation to care or lack of treatment options. In the context of newly available and effective treatment options, this study supports the overall need to accelerate access to HCV screening, diagnostics, and care and treatment services in resource-limited settings in sub-Saharan Africa.

Hepatitis C treatment outcomes using interferon- and ribavirin-based therapy in Kigali, Rwanda.

BACKGROUND: Hepatitis C virus (HCV) treatment data in sub-Saharan Africa are limited. This study was to determine HCV sustained virologic response(SVR) at 24 weeks in patients undergoing HCV therapy in Kigali, Rwanda. METHODS: The paper presents data for all patients treated for HCV with ribavirin/interferon at King Faisal Hospital in Kigali, Rwanda, from 1 January 2007 to 31 December 2014. RESULTS AND CONCLUSIONS: There were 69 evaluable patients. HCV genotype 4(61%, 42/69) predominated. 24-week SVR was 70%(26/37) by per-protocol and 32%(26/69) by intention-to-treat analysis. HCV treatment in Rwanda is feasible. SVR with interferon/ribavirin was acceptable in the per-protocol analysis. Transition to newer direct acting antivirals is urgently needed in Rwanda and sub-Saharan Africa more generally to improve treatment outcomes.

HIV drug resistance mutations among patients failing second-line antiretroviral therapy in Rwanda.

BACKGROUND: Studies of patients failing second-line antiretroviral therapy (ART) in resource-limited settings (RLS) are few. Evidence suggests most patients who appear to be virologically failing do so not due to drug resistance but to poor adherence, which, if properly addressed, could allow continued use of less expensive first- and second-line regimens. Drug resistant mutations (DRMs) were characterized among patients virologically failing second-line ART in Rwanda. METHODS: A total of 128 adult patients receiving second-line ART for at least 6 months were invited to participate; 74 agreed and had HIV-1 viral load (VL) measured. Resistance genotypes were conducted in patients with virological failure (VF; that is, VL ≥1,000 copies/ml). RESULTS: In total, 35 patients met the criteria for VF. The median time on lopinavir/ritonavir-based second-line ART was 2.7 years. Of 30 successful resistance genotype analyses, 13 (43%) had ≥1 nucleoside reverse transcriptase inhibitor (NRTI) mutation, 18 (60%) had at least 1 non-NRTI mutation and 5 (17%) had at least 1 major protease inhibitor mutation. Eleven (37%) had virus without significant mutations that would be fully sensitive to first-line ART; 12 (40%) had DRM to first-line ART but sensitive to second-line ART. Only 7 patients (23%) demonstrated a DRM profile requiring third-line ART. CONCLUSIONS: Among 30 genotyped samples of patients with VF on second-line ART, more than one-third had no significant DRMs, implicating poor adherence as the primary cause of VF. The majority of patients (77%) would not have required third-line ART. These findings reinforce the need for intensive adherence assessment and counselling for patients who appear to be failing second-line ART in RLS.

A neonatal resuscitation curriculum in Malawi, Africa: did it change in-hospital mortality?

Objective. The WHO estimates that 99% of the 3.8 million neonatal deaths occur in developing countries. Neonatal resuscitation training was implemented in Namitete, Malawi. The study's objective was to evaluate the training's impact on hospital staff and neonatal mortality rates. Study Design. Pre-/postcurricular surveys of trainee attitude, knowledge, and skills were analyzed. An observational, longitudinal study of secondary data assessed neonatal mortality. Result. All trainees' (n = 18) outcomes improved, (P = 0.02). Neonatal mortality did not change. There were 3449 births preintervention, 3515 postintervention. Neonatal mortality was 20.9 deaths per 1000 live births preintervention and 21.9/1000 postintervention, (P = 0.86). Conclusion. Short-term pre-/postintervention evaluations frequently reveal positive results, as ours did. Short-term pre- and postintervention evaluations should be interpreted cautiously. Whenever possible, clinical outcomes such as in-hospital mortality should be additionally assessed. More rigorous evaluation strategies should be applied to training programs requiring longitudinal relationships with international community partners.