Paving the Way for the Implementation of a Decision Support System for Antibiotic Prescribing in Primary Care in West Africa: Preimplementation and Co-Design Workshop With Physicians.

BACKGROUND: Suboptimal use of antibiotics is a driver of antimicrobial resistance (AMR). Clinical decision support systems (CDSS) can assist prescribers with rapid access to up-to-date information. In low- and middle-income countries (LMIC), the introduction of CDSS for antibiotic prescribing could have a measurable impact. However, interventions to implement them are challenging because of cultural and structural constraints, and their adoption and sustainability in routine clinical care are often limited. Preimplementation research is needed to ensure relevant adaptation and fit within the context of primary care in West Africa. OBJECTIVE: This study examined the requirements for a CDSS adapted to the context of primary care in West Africa, to analyze the barriers and facilitators of its implementation and adaptation, and to ensure co-designed solutions for its adaptation and sustainable use. METHODS: We organized a workshop in Burkina Faso in June 2019 with 47 health care professionals representing 9 West African countries and 6 medical specialties. The workshop began with a presentation of Antibioclic, a publicly funded CDSS for antibiotic prescribing in primary care that provides personalized antibiotic recommendations for 37 infectious diseases. Antibioclic is freely available on the web and as a smartphone app (iOS, Android). The presentation was followed by a roundtable discussion and completion of a questionnaire with open-ended questions by participants. Qualitative data were analyzed using thematic analysis. RESULTS: Most of the participants had access to a smartphone during their clinical consultations (35/47, 74%), but only 49% (23/47) had access to a computer and none used CDSS for antibiotic prescribing. The participants considered that CDSS could have a number of benefits including updating the knowledge of practitioners on antibiotic prescribing, improving clinical care and reducing AMR, encouraging the establishment of national guidelines, and developing surveillance capabilities in primary care. The most frequently mentioned contextual barrier to implementing a CDSS was the potential risk of increasing self-medication in West Africa, where antibiotics can be bought without a prescription. The need for the CDSS to be tailored to the local epidemiology of infectious diseases and AMR was highlighted along with the availability of diagnostic tests and antibiotics using national guidelines where available. Participants endorsed co-design involving all stakeholders, including nurses, midwives, and pharmacists, as central to any introduction of CDSS. A phased approach was suggested by initiating and evaluating CDSS at a pilot site, followed by dissemination using professional networks and social media. The lack of widespread internet access and computers could be circumvented by a mobile app with an offline mode. CONCLUSIONS: Our study provides valuable information for the development and implementation of a CDSS for antibiotic prescribing among primary care prescribers in LMICs and may, in turn, contribute to improving antibiotic use, clinical outcomes and decreasing AMR.

On estimating the number of people with known HIV positive status.

OBJECTIVE: In 2014, the Joint United Nations Program on HIV and AIDS (UNAIDS) and partners set the '90-90-90 targets'. Many countries are facing the challenge of estimating the first 90. Our objective was to propose an alternative modelling procedure, and to discuss its usefulness for taking into account duplication. RESULTS: For deduplication, we identified two important ingredients: the probability for an HIV+ person of being re-tested during the period and average number of HIV+ tests. Other adjusted factors included: the false positive probability; the death and emigration probabilities. The uncertainty of the adjusted estimate was assessed using the plausibility bounds and sensitivity analysis. The proposed method was applied to Cameroon for the period 1987-2016. Of the 560,000 people living with HIV estimated from UNAIDS in 2016; 504,000 out to know their status. The model estimates that 380,464 [379,257, 381,674] know their status (75.5%); thus 179,536 who do not know their status should be sought through the intensification of testing. These results were subsequently used for constructing the full 2016 Cameroon HIV cascade for identifying programmatic gap, prioritizing the resources, and guiding the strategies of the 2018-2022 National Strategy Plan and funding request.

Prevalence of tubulopathy and association with renal function loss in HIV-infected patients.

BACKGROUND: The incidence of chronic kidney disease (CKD) is 10 times higher in human immunodeficiency virus (HIV)-infected patients than in the general population. We explored the prevalence and determinants of proximal tubular dysfunction (PTD) in HIV-infected individuals, and assessed the impact of the tubulopathy on the estimated glomerular filtration rate (eGFR) outcome. METHODS: A cohort study was performed on 694 outpatients followed in a French centre to analyse the prevalence of PTD, the diagnosis performance of screening tools and the associated factors. eGFR was prospectively evaluated to analyse the predictive value of the tubulopathy on eGFR decrease. RESULTS: At inclusion, 14% of the patients presented with PTD and 5% with CKD. No individual tubular marker, including non-glomerular proteinuria, glycosuria dipstick or hypophosphataemia, registered sufficient performance to identify PTD. We found a significant interaction between tenofovir disoproxil fumarate exposure and ethnicity (P = 0.03) for tubulopathy risk. Tenofovir disoproxil fumarate exposure was associated with PTD in non-Africans [adjusted odds ratio (aOR) = 4.71, P < 10-3], but not in patients of sub-Saharan African origin (aOR = 1.17, P = 0.73). Among the 601 patients followed during a median of 4.3 years, 13% experienced an accelerated eGFR decline. Unlike microalbuminuria and glomerular proteinuria, tubulopathy was not associated with accelerated eGFR decline. CONCLUSION: PTD is not rare in HIV-infected individuals but is less frequent in sub-Saharan African patients and is associated with tenofovir disoproxil fumarate exposure only in non-Africans. Its diagnosis requires multiple biochemical testing and it is not associated with an accelerated eGFR decline.

[Vulnerability of male prisoners to HIV /AIDS in Ouagadougou/ Burkina Faso]. / La vulnérabilité des détenus hommes face au VIH/sida à Ouagadougou (Burkina Faso).

OBJECTIVE: To evaluate the vulnerability of male prisoners to HIV, risk behaviour and access to prevention. METHODS: This cross-sectional descriptive study was conducted in july and August 2012 in Ouagadougou Prison in Burkina Faso. Two trained investigators collected data by means of individual interviews in the prison visiting room using a questionnaire administered to male inmates 18 years and older, imprisoned for more than three months. Two focus groups were conducted with prison guards and healthcare personnel. RESULTS: A total of165 male prisoners were interviewed. The mean prison sentence was 19 months, the median age of the inmates was 28years and 45% of them were illiterate. About4% of male prisoners reported having had homosexual relations during their imprisonment. However, data indicate underreporting and denial of homosexual behaviour by prisoners. 49% of prisoners shared razors or razorblades in prison. None of the interviewees reported injected drug use or tattoos in prison. The majority (84%) of prisoners had a good knowledge of HIVjAIDS and 6% were aware of the risk of sexually transmitted infections. Only 5% of prisoners had had a screening test during their stay in prison. CONCLUSION: Prison conditions, homosexual behaviour and absence of condoms in prison accentuate the vulnerability of prisoners to HIV j AIDS. Implementation of a prevention programme and management HIV-positive prisoners would help to reduce significantly the risk of HIV transmission in prison.

The vulnerability of men to virologic failure during antiretroviral therapy in a public routine clinic in Burkina Faso.

INTRODUCTION: Gender differences in antiretroviral therapy (ART) outcomes are critical in sub-Saharan Africa. We assessed the association between gender and virologic failure among adult patients treated in a public routine clinic (one of the largest in West Africa) in Burkina Faso. METHODS: We performed a case-control study between July and October 2012 among patients who had received ART at the Bobo Dioulasso Day Care Unit. Patients were eligible if they were 15 years or older, positive for HIV-1 or HIV-1+2, and on first-line ART for at least six months. Cases were all patients with two consecutive HIV loads >1000 copies/mL (Biocentric Generic or Abbott Real Time assays), or one HIV load >1000 copies/mL associated with immunologic or clinical failure criteria. Controls were all patients who only had HIV loads <300 copies/mL. The association between gender and virologic failure was assessed using a multivariate logistic regression, adjusted on age, level of education, baseline CD4+ T cell count, first and current antiretroviral regimens and time on ART. RESULTS: Of 2303 patients (74.2% women; median age: 40 years; median time on ART: 34 months), 172 had virologic failure and 2131 had virologic success. Among the former, 130 (75.6%) had confirmed virologic failure, 38 (22.1%) had viro-immunologic failure, and four (2.3%) had viro-clinical failure. The proportion of men was significantly higher among the cases than among the controls (37.2% vs. 24.9%; p<0.001). Compared to controls, cases were also younger, more immunodeficient at ART initiation, less likely to receive a protease inhibitor-based antiretroviral regimen and had spent a longer period of time on ART. After adjustment, male gender remained strongly associated with virologic failure (odds ratio 2.52, 95% CI: 1.77-3.60; p<0.001). CONCLUSIONS: Men on ART appeared more vulnerable to virologic failure than women. Additional studies are needed to confirm the poorer prognosis of men in this setting and to determine the causes for their vulnerability in order to optimize HIV care. From now on, efforts should be made to support the adherence of men to ART in the African setting.

Tubulointerstitial nephropathies in HIV-infected patients over the past 15 years: a clinico-pathological study.

BACKGROUND AND OBJECTIVES: The therapy and outcome of HIV infection have dramatically changed over the last 15 years, resulting in a change in renal complications. This study analyzed the characteristics of HIV-infected patients and biopsy-proven tubulointerstitial nephropathies to define disease patterns and therapeutic implications. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A clinico-pathologic retrospective study of 59 consecutive renal biopsies showing predominant tubular and/or interstitial lesions in HIV-infected patients referred to the nephrology department between 1995 and 2011 was performed. HIV-associated nephropathy and vascular diseases were excluded from the study. RESULTS: Tubulointerstitial nephropathies accounted for 26.6% of 222 native renal biopsies performed in HIV-infected patients. Two pathologic groups were analyzed, tubulopathy and interstitial nephritis, which represented 49% and 51% of tubulointerstitial nephropathies, respectively. Most patients presented with AKI (76.3%) and high-grade proteinuria (57.7%). Drug-related nephrotoxicity was the leading cause (52.5%). Alternative etiologies included infections (15.2%), dysimmune disorders (8.5%), malignancies (3.4%), and chronic (10.2%) and acute (10.2%) tubulointerstitial nephropathies of undetermined origin. Tubulopathy was strongly associated with antiretroviral drug toxicity (75.9%) and mostly caused by tenofovir (55.2%), which was associated with proximal tubular dysfunction (87.5%), overt Fanconi's syndrome (37.5%), and nephrogenic diabetes insipidus (12.5%). Interstitial nephritis was associated with a broader spectrum of pathologic lesions and etiologies. CONCLUSIONS: In this series, tubulointerstitial nephropathies accounted for 26.6% of renal diseases in HIV-infected patients. Considering the therapeutic implications of diagnoses of drug toxicity, infection, and dysimmune syndromes, this study underscores the importance of monitoring renal parameters in HIV-infected patients and points to the relevance of kidney biopsy to allow an accurate diagnosis.

Factors predictive of virological failure on atazanavir in 310 HIV-infected patients.

We examined factors associated with virological failure in 310 HIV-infected patients receiving atazanavir (ATV). Independent links were identified with virological failure under ATV: virological failure previous history (P = 0.006) and ATV underdosing (P = 0.04). A maintenance therapy was protective (P = 0.01). The optimal therapeutic ranges of ATV concentration were found to be from 300 ng/ml (or 180 for patients treated with maintenance therapy) to 650 ng/ml for C24 and from 1000 ng/ml (or 500 for patients treated with maintenance therapy) to 2000 ng/ml for C12.

Comparison of elastography, serum marker scores, and histology for the assessment of liver fibrosis in hepatitis B virus (HBV)-infected patients in Burkina Faso.

Liver fibrosis (LF) must be assessed before talking treatment decisions in hepatitis B. In Burkina Faso, liver biopsy (LB) remains the "gold standard" method for this purpose. Access to treatment might be simpler if reliable alternative techniques for LF evaluation were available. The hepatitis B virus (HBV)-infected patients who underwent LB was invited to have liver stiffness measurement (Fibroscan) and serum marker assays. Fifty-nine patients were enrolled. The performance of each technique for distinguishing F0F1 from F2F3F4 was compared. The area under receiver operating characteristic (AUROC) curves was 0.61, 0.71, 0.79, 0.82, and 0.87 for the aspartate transaminase to platelet ratio index (APRI), Fib-4, Fibrotest, Fibrometre, and Fibroscan. Elastometric thresholds were identified for significant fibrosis and cirrhosis. Combined use of Fibroscan and a serum marker could avoid 80% of biopsies. This study shows that the results of alternative methods concord with those of histology in HBV-infected patients in Burkina Faso. These alternative techniques could help physicians to identify patients requiring treatment.

Chagas disease, France.

Chagas disease (CD) is endemic to Latin America; its prevalence is highest in Bolivia. CD is sometimes seen in the United States and Canada among migrants from Latin America, whereas it is rare in Europe. We report 9 cases of imported CD in France from 2004 to 2006.

Acute renal failure associated with immune restoration inflammatory syndrome.

BACKGROUND: A 30-year-old HIV-infected woman presented with fever and abdominal pain 4 days after initiation of highly active antiretroviral therapy (HAART), and 1 month after initiation of antimicrobial therapy for Mycobacterium tuberculosis infection. A diagnosis of immune restoration inflammatory syndrome (IRIS) was considered, and corticosteroids were started. Steroid therapy doses were progressively tapered, during which time the patient developed renal failure with enlarged kidneys. A renal biopsy showed acute interstitial nephritis. Extensive investigations failed to detect active infection. The efficacy of HAART was attested by increased CD4+ cell counts and undetectable viral replication. INVESTIGATIONS: Physical examination, plasma viral load and CD4+ cell count, abdominal and renal ultrasound, renal and peritoneal biopsies, renal and liver function, chest X-ray, and bronchoalveolar lavage culture. DIAGNOSIS: Acute renal failure secondary to IRIS. MANAGEMENT: Prednisone therapy.

Outcome and prognosis factors in HIV-infected hemodialysis patients.

HIV-infected patients who are on hemodialysis have a worse prognosis than noninfected patients who are on hemodialysis. Their outcome in the highly active antiretroviral therapy (HAART) era remains unclear. Outcomes in patients who were enrolled in the French Dialysis in HIV/AIDS (DIVA) cohort were determined in a 2-yr prospective follow-up. All HIV-infected patients who were on hemodialysis in France on January 1, 2002, were included and followed prospectively until January 1, 2004. Patients' survival was examined by Kaplan-Meier method, and mortality risk factors were examined using uni- and multicovariate analyses. Survival was compared with that of 584 hemodialysis patients who did not have HIV or diabetes and were enrolled in the French Dialysis Outcomes and Practice Patterns Study II (DOPPS II) in the same period (after standardization for the average age, gender, and ethnicity of the DIVA cohort). A total of 27,577 patients were receiving hemodialysis in France at the beginning of the study; 164 (0.59%) were infected with HIV, 72% were male, mean age was 44.8 +/- 10.9 yr, and 65% were black. The 2-yr survival rate was 89 +/- 2% and statistically indistinguishable from the survival of the French cohort extracted from the DOPPS II study. Significant mortality risk factors were low CD4 cell count (hazard ratio [HR] 1.4/100 CD4 cells per mm(3) lower), high viral load (HR 2.5/1 Log per ml), absence of HAART (HR 2.7), and a history of opportunistic infection (HR 3.7), the last two being independent (HR 2.6 and 3.6, respectively). Survival of HIV-infected patients who are hemodialysis has greatly improved. A prospective cohort of paired hemodialysis patients with and without HIV is required to compare better their mortality in the HAART era.

Antiretroviral therapy in public and private routine health care clinics in Cameroon: lessons from the Douala antiretroviral (DARVIR) initiative.

A review of the hospital charts for 788 patients treated in 19 public and private clinics in Cameroon showed that clinical follow-up visits, biologic follow-up visits, and drug supply were irregular and that many patients interrupted treatment. Virological and immunologic effectiveness of therapy was as expected in patients for whom results were available.

The clinical characteristics of HIV-infected patients receiving dialysis in France between 1997 and 2002.

BACKGROUND: In 1997, 0.38% of dialysis patients in France were infected by human immunodeficiency virus (HIV). No prevalence data were available in France since the widespread introduction of highly active antiretroviral therapy. METHODS: This was a cross-sectional epidemiologic survey. A questionnaire was sent to all French dialysis centers in July 2002. The centers that did not respond were sent 3 additional mailing reminders. Finally, the nonresponding centers were called early in 2004. RESULTS: Of the 27,577 patients on hemodialysis and 587 patients on peritoneal dialysis, 190 patients (0.67%) were infected by HIV. HIV-associated nephropathy was the cause of renal failure in 39.8% patients. Mean age was 44.6 +/- 10.9 years, the mean duration of dialysis was 4.9 +/- 5.9 years, the mean known duration of HIV infection was 8.9 +/- 5.6 years. Eighty-two percent of patients received antiretroviral therapy (ART). Fifty-eight percent of ART-treated patients had an undetectable HIV plasma viral load with a median CD4+ T-cell count 303/mm(3). CONCLUSION: The prevalence of HIV infection among French dialysis patients was 0.67% in late 2002, a 79% increase since 1997. Possible reasons for this large increase include increased access to dialysis, better general status of HIV dialysis patients, and increasing proportion of patients originating from Africa and the Caribbean. The current efficacy of ART makes renal transplantation a realistic option for these young patients.

Splenic infarction during acute malaria.

Malaria is the most frequent cause of fever among travellers returning from tropical countries. Each year about 7000 cases are notified in France, of which 90% are due to Plasmodium falciparum. We describe the case of a Caucasian female patient with no previous exposure to malaria in whom splenic infarction occurred during effective antimalarial treatment for initially uncomplicated acute malaria. Management was restricted to close clinical monitoring and analgesia (subcutaneous morphine). Imaging abnormalities resolved within a few months. We found seven other such cases in the literature. All seven patients were younger and splenic infarction occurred later than in the case we describe. Clinical outcome was favourable in all the cases. It is noteworthy that this rare complication can occur despite appropriate antimalarial prophylaxis and treatment. There are no known predictive signs. Clinicians must be aware that left hypochondrial pain occurring during treatment for acute malaria may be due to splenic infarction.

High variability of plasma drug concentrations in dual protease inhibitor regimens.

Ritonavir (RTV) strongly increases the concentrations of protease inhibitors (PIs) in plasma in patients given a combination of RTV and another PI. This pharmacological interaction is complex and poorly characterized and shows marked inter- and intraindividual variations. In addition, RTV interacts differently with saquinavir (SQV), indinavir (IDV), amprenavir (APV), and lopinavir (LPV). In this retrospective study on 542 human immunodeficiency virus-infected patients, we compared inter- and intraindividual variability of plasma PI concentrations and correlations between the C(min) (minimum concentration of drug in plasma) values for RTV and the coadministered PI C(min) values. Mean RTV C(min)s are significantly lower in patients receiving combinations containing APV or LPV than in combinations with SQV or IDV. With the most common PI dose regimens (600 mg of IDV twice a day [BID], 800 mg of SQV BID, and 400 mg of LPV BID), the interindividual C(min) variability of patients treated with a PI and RTV seemed to be lower with APV and LPV than with IDV and SQV. As regards intraindividual variability, APV also differed from the other PIs, exhibiting lower C(min) variability than with the other combinations. Significant positive correlations between RTV C(min) and boosted PI C(min) were observed with IDV, SQV, and LPV, but not with APV. Individual dose adjustments must take into account the specificity the pharmacological interaction of each RTV/PI combination and the large inter- and intraindividual variability of plasma PI levels to avoid suboptimal plasma drug concentrations which may lead to treatment failure and too high concentrations which may induce toxicity and therefore reduce patient compliance.