CROI 2016 Abstract eBook

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Poster Abstracts

Results: To date, 18 subjects started ART with EVG/c-FTC-TDF. Twelve subjects have achieved at least 24 weeks of follow-up. The majority are female (83%), with a median age of 47.5 years at enrollment. There were no deaths, no loss to follow up, and no AIDS-associated clinical events. There was one withdrawal. Median baseline CD4 count was 386 cells/ ul (IQR: 335-465) and increased to 452 cells/ul (IQR: 354-534) by week 24. All subjects had baseline viral loads of fewer than 50 copies/ml of plasma, including five subjects who had viral loads below the reproducible limit of detection (10 copies/ml). All patients had achieved undetectable plasma viral loads by week 4 and maintained them. EVG/c-FTC-TDF was generally well tolerated and there were no grade 3-4 adverse events. Adherence was good by self-report and pill count. Conclusions: Long-term outcomes of HIV-2 infected patients on ART in West Africa are suboptimal and new therapeutic options are needed. Initial data suggest that EVG/c- FTC-TDF, a once-daily single-tablet regimen, is safe, effective, and well-tolerated in this population. Our findings support the use of integrase inhibitor-based regimens for HIV-2 treatment. 962 Severe Neutropenia in HIV-Infected People on Antiretroviral Therapy inWest Africa Charline Leroi 1 ; Eugene Messou 2 ; Albert Minga 3 ; Adrien Sawadogo 4 ; Joseph Drabo 5 ; Moussa Maiga 6 ; Marcel Zannou 7 ; Moussa Seydi 8 ; Francois Dabis 1 ; Antoine Jaquet 1 1 INSERM U897, ISPED, Univ de Bordeaux, Bordeaux, France; 2 CePReF, ACONDA, Abidjan, Côte d’Ivoire; 3 Cntr Médical de Suivi de Donneurs de Sang /CNTS/PRIMO-CI, Abidjan, Côte d’Ivoire; 4 CHU, Souro Sanou, Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso; 5 CHU Yalgado Ouedraogo, Ouagadougou, Burkina Faso; 6 Service d`Hépato-Gastro-Entérologie, Hosp Gabriel Touré, Bamako, Mali; 7 Cntr de Prise en Charge des Personnes Vivant Avec le VIH, CHNU, Cotonou, Benin; 8 CHU de Fann, Dakar, Senegal Background: In Sub-Saharan Africa, antiretroviral therapy (ART) with potential toxicity such as Zidovudine (AZT) is still massively prescribed in HIV-infected patients. Nevertheless, little information is available on adverse drug reactions such as neutropenia in real life conditions. This study aimed at estimating the incidence of severe neutropenia and associated factors after ART initiation in five West African countries. Methods: A retrospective cohort analysis was conducted within the international epidemiologic database to evaluate AIDS (IeDEA) collaboration in West Africa. All HIV-infected adults, starting ART between 2002 and 2014, with a baseline and at least one follow-up absolute neutrophil count (ANC) measurement were eligible. The main outcome was the first episode of severe neutropenia (ANC <750 cells/mm 3 ). Incidence was estimated with 95% confidence interval (CI) according to age, gender, clinic, hemoglobin, CD4 count, clinical stage, ART duration. A Cox proportional hazard model identified the factors associated with the outcome and associations were expressed by adjusted hazard ratios (aHR). Results: Between 2002 and 2014, 9,426 HIV-infected adults were enrolled in eight clinics in Benin, Burkina Faso, Cote d’Ivoire, Mali and Senegal at a median age of 37 years [interquartile range (IQR) 31-44] and with a median participation time of 12 months in [IQR 6-19]. Since 2008, more than 60% of the 4,911 patients enrolled initiated an AZT-based ART regimen (Figure 1). The crude incidence of first severe neutropenia episode was 9.1 per 100 person-years (CI: 8.6-9.8). Factors associated with severe neutropenia were the cumulated exposure to AZT <6 months (aHR=2.2; CI: 1.8-2.6), ≥6-12 months (aHR=2.1; CI: 1.6-2.8) and ≥12 months (aHR=1.6; CI: 1.2-2.2) [Ref. no AZT exposure], CD4 count <350 cells/mm 3 (aHR=1.3; CI: 1.1-1.5), advanced clinical stage (aHR=1.2; CI: 1.0-1.4), an ANC ≥750-1000 cells/mm 3 (aHR=2.5; CI: 2.0-3.1) and an ANC ≥1000-1300 cells/mm 3 (aHR=1.5; CI: 1.3-1.8) [Ref. ANC ≥1300 cells/mm 3 ] at ART initiation. Of the 555 patients on AZT with incident severe neutropenia, 51 (9%) switched to an alternative ART following severe neutropenia. Conclusions: The incidence of severe neutropenia after ART initiation among HIV-infected adults in West Africa is high and associated with AZT exposure. In a context where cytotoxic drugs such as AZT are still widely prescribed, future efforts are needed to scale-up access to less toxic drugs such as tenofovir according to recent WHO recommendations.

Poster Abstracts

963 Efavirenz Toxicity Manifesting As Cerebellar Ataxia: Case Series From South Africa EbrahimVariava 1 ; Farai R. Sigauke 2 ; Petudzai Muchichwa 2 ; Gary Maartens 3 ; Neil Martinson 4 1 Klerksdorp/Tshepong Hosp, Klerksdorp, South Africa; 2 Klerksdorp Tshepong Hosp Complex, Northwest Dept of Hlth, Klerksdorp, South Africa; 3 Univ of Cape Town, Cape Town, South Africa; 4 Perinatal HIV Rsr Unit, Diepkloof, South Africa Background: WHO treatment guidelines recommend efavirenz (EFV) as the backbone of first line antiretroviral therapy (ART). Fixed dose combination (FDC), which contain efavirenz 600mg, improve adherence but dose adjustments cannot be made easily. EFV commonly causes early neuro-psychiatric adverse events. We present seven cases with late EFV toxicity causing severe cerebellar ataxia. Methods: Consecutive HIV-infected adults taking EFV-containing combination ART admitted to hospital with cerebellar ataxia were included in this case series. Patients were neurologically examined, and all had lumbar punctures, chest x-rays, and CT scans of the brain. EFV concentrations (therapeutic levels 1-4mg/l), serum vitamin B12 levels, thyroid stimulating hormone (TSH) and syphilis serology were done on all patients to exclude other common causes of ataxia. We did not assess EFV metabolizer genotype. Results: We identified seven women with severe cerebellar signs who were on ART for a median period of 2 years (IQR:1.5-5.5). All had staccato speech, severe truncal and limb ataxia, and were unable to walk or sit unaided, but none had nystagmus. Their median weight was 34kg (IQR:29.7-35.3); median CD4 count 299 (IQR:258-300); all were virologically suppressed at admission and none reported alcohol use. Two were on rifampin-containing TB treatment, and one had epilepsy treated with phenytoin. All chest x-rays were normal. CT scans were either normal or showed generalised atrophy. All patients’ TSH, B12, and syphilis serology were normal. Six patients’ plasma EFV level was >20 mg/l (the upper limit of detection), and one was 18 mg/l. Ataxia resolved in all patients after withdrawal of EFV at a median time of 2 months (IQR1.25-4) after withdrawal of EFV. The patient taking phenytoin also had concurrent elevated phenytoin levels, which was stopped but the ataxia resolved only after subsequent EFV withdrawal. Conclusions: As far as we are aware, this is the first report of severe cerebellar ataxia caused by toxic EFV dosages likely related to treatment with FDCs occurring after years of therapy. All patients had low weight and were treated with 600 mg EFV in FDC and had extremely high EFV concentrations, suggesting they were genetic slowmetabolizers. Clinicans should be aware of this presentation of EFV toxicty. We recommend that patients weighing <40kg receive lower doses of EFV or, in areas where only FDC is available, not receive EFV FDCs.

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CROI 2016