CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Results: 56 of 451 participants were diagnosed with TB during a median study follow-up of 4.6 yrs (3.1 events/100 person-years (PYs), 95% CI: 2.4 – 4.1). 10 (18%) cases were culture-confirmed, the remainder were clinical diagnoses. 43 of 56 (77%) cases were pulmonary, 5 (9%) were non-pulmonary, and 8 (14%) were immune reconstitution inflammatory syndrome TB. In a multivariable Poisson regression, TB incidence was higher in children <1yr at entry (p=0.05) but did not differ significantly by baseline CD4% (< vs. ≥ 25%, p=0.49) or randomized ART arm (LPV/r vs. NVP, p=0.21). Most TB cases occurred within 6m of study entry (13.4 events/100PYs), with rates decreasing over the follow-up period ( ≤ 2.9 events/100 PYs, p<0.001). ART was modified in 45/56 (80%) children: most (48%) switched to RTV-boosted LPV/r and 7 (13%) to efavirenz. 48 of the 56 children starting TB therapy had HIV-1 RNA measurements 10-36 wks (value closest to 24 wks) after starting TB therapy; 63% had HIV-1 RNA < 400 cp/ml before TB therapy vs. 75% after (p=0.11). 6/56 HIV/TB co-infected children (11%) experienced grade ≥ 3 adverse events, including 3 with decreased ANC, 1 with abnormal SGPT, 1 with low hemoglobin, and 1 with convulsions. Conclusions: TB disease remains a major challenge in HIV infected children living in high TB burden countries. Age <1 yr and the first 6m following initiation of ART are associated with higher risk of MTB disease. Superboosting of LPV/r was the most common ART change, regardless of initial ART regimen, and TB therapy did not affect viral suppression. 940 Safety of Rifabutin in HIV/TB-Coinfected Children on Protease Inhibitor-Based ART Holly E. Rawizza 1 ; Kristin M. Darin 2 ; Kimberly K. Scarsi 3 ; Biobele Brown 4 ; Regina Oladokun 4 ; Nkiru David 5 ; Sulaimon Akanmu 6 ; Oluremi Olaitan 7 ; Prosper Okonkwo 7 ; Phyllis Kanki 8 On behalf of the APIN PEPFARTeam 1 Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, US; 2 Northwestern University, Feinberg School of Medicine, Chicago, IL, US; 3 University of Nebraska Medical Center, Omaha, NE, US; 4 University College Hospital, Ibadan, Nigeria; 5 National Institute of Medical Research, Lagos, Nigeria; 6 Lagos University Teaching Hospital, Lagos, Nigeria; 7 AIDS Prevention Initiative in Nigeria, Abuja, Nigeria; 8 Harvard School of Public Health, Boston, MA, US Background: Tuberculosis (TB) is the leading cause of death among HIV-infected children, yet treatment options for those requiring protease inhibitor (PI)-based antiretroviral therapy (ART) are suboptimal. Rifabutin is the rifamycin of choice for adults on PI-based ART; but only one study to-date has evaluated its use among children on PI-based ART, and 2 of 6 children developed treatment-limiting neutropenia. Methods: Since 2008, rifabutin has been available for HIV/TB co-infected children requiring PI-based ART in the Harvard/APIN PEPFAR program in Nigeria. We performed a retrospective analysis to evaluate laboratory (absolute neutrophil count (ANC), hemoglobin, platelet count, alanine aminotransferase (ALT), and creatinine) and clinical toxicities at baseline (prior to rifabutin) and during rifabutin therapy. Toxicities were graded using the DAIDS pediatric adverse event scales. Results: Between 2008-2012, 42 children received rifabutin-based TB therapy with PI (lopinavir/ritonavir)-based ART: 45%were female with median (IQR) baseline age of 1.5 (0.8-4.6) years, CD4 of 437 (226-779) cells/mm 3 and CD4% of 14% (8-22%); 19%were at WHO clinical stage 4; and 48%were already on ART at rifabutin start. 86% completed the expected rifabutin course with resolution of TB symptoms. At baseline, 24% of children had grade 3 or 4 neutropenia (n=2), anemia (n=7), or both (n=1), which resolved or improved on rifabutin in all except 1 with stable grade 3 anemia. During rifabutin therapy, 12% developed grade 3 or 4 toxicity: grade 4 neutropenia (n=1) developed after 1 month on rifabutin, but resolved at month 4 despite ongoing therapy; grade 3 neutropenia (n=2) developed after 3 and 5 months on rifabutin and resolved following completion; grade 4 anemia (n=1) developed in 1 patient with underlying hemoglobinopathy and persisted after rifabutin completion; and grade 3 thrombocytopenia (n=1) developed after 3 months on rifabutin and persisted after treatment completion. Neither grade 3 or 4 abnormalities in ALT or creatinine nor significant clinical toxicities were reported. Conclusions: With clinical and laboratory monitoring, our data suggest that rifabutin is a safe option for TB therapy among children on PI-based ART. Severe toxicities were more frequent prior to rather than during rifabutin therapy. Infrequent severe toxicities observed with rifabutin resolved following completion of therapy in most cases. Additional research is urgently needed to further evaluate rifabutin safety and efficacy among children. 941 Skin Complaints in African Children Randomized to Stop or Continue Cotrimoxazole Andrew Prendergast 1 ; Mutsa F. Bwakura Dangarembizi 2 ; Peter Mugyenyi 3 ; Joseph Lutaakome 4 ; Adeodata Kekitiinwa 5 ; Diana M. Gibb 6 ; SarahWalker 6 On behalf of the ARROWTrialTeam 1 Queen Mary University of London, London, United Kingdom; 2 University of Zimbabwe, College of Health Sciences, Harare, Zimbabwe; 3 JCRC, Kampala, Uganda; 4 MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda; 5 Baylor-Uganda, Kampala, Uganda; 6 MRC Clinical Trials Unit at University College London, London, United Kingdom Background: Recurrent skin complaints are common in HIV-infected children in sub-Saharan Africa. Skin infections tend to be more severe and atypical, respond less well to treatment and relapse more frequently in HIV-infected compared to uninfected children, making management challenging and affecting quality of life. Whether cotrimoxazole (CTX) has a role in preventing skin conditions in HIV-infected children is not well reported from settings where microbial resistance rates to CTX are high. Methods: Of 1206 children in the ARROW trial in Uganda/Zimbabwe, 758 were randomized to stop (n=382) or continue (n=376) daily CTX (open-label) after median(IQR) 2.1(1.8,2.2) years on ART. Eligible children were aged >3 years, on ART >96 weeks, currently on CTX, using insecticide-treated bednets if living in malaria-endemic areas and had no previous PCP. During 6-weekly clinic visits, a nurse symptom screen was undertaken. Skin complaints were categorized blind to randomization as bacterial infection; fungal infection; viral infection; dermatitis; papular pruritic eruptions (PPE); or other (blisters, desquamation, ulcers and urticaria). Proportions of children ever reporting each skin complaint were compared across randomized groups using logistic regression. Results: At randomization, median(IQR) age was 7(4,11) years and CD4 was 33%(26,39) (vs 13%(8,18) pre-ART); 25%/59%/14% children had WHO stage 2/3/4 disease. Fewer children continuing CTX ever reported bacterial skin infections over median 2 years follow-up (15% vs 33% stop, OR=0.36 [95%CI 0.25-0.51] P<0.001), with similar marginal trends for PPE (10% vs 14%, OR=0.64 [0.42,1.01] P=0.06) and other skin complaints (20% vs 23%, OR=0.61 [0.34,1.10] p=0.10). There was no evidence of difference in fungal (P=0.41) or viral (P=0.21) infections or dermatitis (P=0.98). Bacterial skin infections were also reported at significantly fewer clinic visits between 6-120 weeks post-randomization (1.2% vs 3.0%, P<0.001). Independent of CTX, bacterial skin infections were more common in younger children, those from rural Entebbe or Harare vs urban Kampala, and those with lower height-for-age or CD4<500 at CTX randomisation (all P<0.05). Conclusions: In addition to the significant benefits previously reported for reduced hospitalization/death, prolonged CTX prophylaxis in children on long-term ART reduces bacterial skin complaints despite high rates of microbial resistance and good immune reconstitution on ART, highlighting an additional benefit for CTX in sub-Saharan Africa. 942 Disease Progression and Response to Treatment in Vertically HIV/HVC Co-infected Patients Talía Sainz 1 ; Carolina Fernández McPhee 2 ; Santiago Jimenez de Ory 1 ; Pablo Rojo 3 ; Maria del Carmen Otero 4 ; Milagros Garcia Lopez-Hortelano 5 ; Olaf Neth 7 ; Jose Beceiro 8 ; Maribel GonzálezTomé 3 ; María Luisa Navarro 6 On behalf of the Spanish Cohort of HIV-Infected Children and Adolescents (CoRISpe) 1 Hospital Universitario Gregorio Marañón, Madrid, Spain; 2 Hospital Ramón y Cajal, SEIM-Gesida, Madrid, Spain; 3 Hospital 12 de Octubre, Madrid, Spain; 4 Hospital La Fe, Valencia, Spain; 5 Hospital La Paz, Madrid, Spain; 6 Hospital Gregorio Marañón, Madrid, Spain; 7 Hospital Virgen del Rocio, Sevilla, Spain; 8 Hospital de Alcalá, Alcalá de Henares, Spain Background: Background: HVC co-infection is a predictor of adverse outcomes in HIV-infected patients. However, few data are available regarding the natural history of vertically HIV/HVC co-infected children. We analyzed the situation of a cohort of perinatally HIV/HVC co-infected patients and their response to HVC treatment.

Poster Abstracts

563

CROI 2015