CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

40-41 per 1000 person-years) for uninfected. In bivariate analyses, relative to uninfected Veterans, joint dislocation and TBI were less common among HIV+ (1.2% vs 1.7%, p<0.001; and 1.2% vs 1.4%, p<0.001, respectively) whereas hip fracture and fragility fractures were more common (hip fractures: 1.3% vs 0.7%, p<0.001; fragility fractures: 8.0% vs 7.4%, p<0.001, respectively). In fully adjusted models, relative to those who did not fall, those who fell had a substantially increased risk of serious injury: HIV+ (OR 4.14; 95% CI 3.86, 4.44) and uninfected (OR 1.42; 95% CI 1.35, 1.49). Conclusion: Among those 50+ years of age, HIV+ are more likely to fall and more likely to experience serious injury, commonly in the form of fracture, after they fall compared to uninfected individuals. 705 SCREENING AND PREEMPTIVE ANTIFUNGAL THERAPY FOR SUBCLINICAL CRYPTOCOCCAL DISEASE Admire Hlupeni, Rhoderick Machekano, Kathryn F. Boyd, Takudzwa Chagumaira, Primrose Nyamayaro, Chiratidzo E. Ndhlovu , Azure T. Makadzange University of Zimbabwe, Harare, Zimbabwe Background: Serum cryptococcal antigen (sCrAg) screening and pre-emptive antifungal treatment is recommended for individuals with HIV and CD4 ≤100 cells/μl by the World Health Organization. However the prevalence of subclinical antigenemia, optimal management of positive individuals, and outcomes following ‘screen and treat’ are poorly defined. Methods: In this multicenter, prospective implementation science cohort study, HIV infected individuals with CD4 counts ≤100 cells/μl and without symptomatic meningitis, enrolled at 20 outpatient centers in Harare underwent sCrAg testing. Lumbar puncture (LP) was recommended to sCrAg positive participants. Hospitalization and treatment with intravenous (IV) amphotericin B and high dose fluconazole was recommended to cerebrospinal fluid (CSF) CrAg positive participants; sCrAg positive participants who declined LP were treated with high dose fluconazole monotherapy. ART and HIV disease management was done by the primary HIV provider. Recommendations were made to initiate ART immediately in sCrAg negative and 4 weeks after initiating antifungal therapy in sCrAg positive participants. Primary endpoints were survival at 6 and 12-months. Outcomes assessed included sCrAg seroprevalence, and prevalence of disseminated cryptococcal disease as determined by positive blood or CSF cultures. Results: Between April 2015 and June 2016 2016, 1320 participants were enrolled; 130 (9.8%) were sCrAg positive with a median titre of 1:20. Sixty-six (50.8%) of sCrAg participants consented to an LPs; 11 (16.7%) had evidence of CNS disease dissemination. Blood cultures were positive in 10/129 (7.5%) sCrAg positive participants. Overall survival rate at 12-months was 83.9% (95% CI: 81.5-86.0) and 76.1 % (95% CI: 67.1 – 83.0; p=0.011) in sCrAg negative and positive participants respectively. Factors associated with increased mortality were positive sCrAg, positive CSF CrAg, CD4 count, and time to ART initiation in sCrAg negative. All cause mortality and sCrAg titre did not differ among sCrAg positive participants that received LPs and IV amphotericin when indicated, and those that declined LP. Conclusion: The prevalence of subclinical antigenemia is high and a positive sCrAg remains an important risk factor for mortality. Disease dissemination is evident despite subclinical disease; however in this cohort LPs and IV therapy did not markedly improve survival compared with high dose fluconazole alone. Early initiation of ART in sCrAg negative individuals improved survival. 706 SCREENING FOR TALAROMYCES AND CRYPTOCOCCAL ANTIGENEMIA IN AIDS PATIENTS IN GUANGDONG Linghua Li 1 , Liya Li 1 , Yaozu He 1 , Haodi Wang 1 , Kaiyin He 1 , Xiaoping Tang 1 , Thuy Le 3 , Weiping Cai 2 1 Guangzhou Eighth People’s Hospital, Guangzhou, China, 2 Duke University, Durham, NC, USA Background: Talaromycosis and cryptococcosis are the leading causes of morbidity and mortality in patients with advanced HIV disease in Southern China. We conducted a prospective study using commercially available antigen detection assays in Guangdong located in Southern China to determine disease burden and clinical significance of antigenemia to inform disease control strategies. Methods: This is an analysis of an ongoing prospective study enrolling antiretroviral-naive patients aged ≥18 with CD4 count ≤100 cells/μl who continuously registered for care in Guangzhou Eighth People’s Hospital between January 2016 and December 2016. Talaromycosis was screened using a novel

talaromyces Mp1p antigen enzyme immunoassay (Mp1p EIA) and an aspergillus galactomannan (GM) test. Cryptococcosis was screened using a cryptococcal antigen (CrAg) test. Management and follow up of patients were according to the standard HIV care. Results: A total of 236 patients have been recruited: 194 (83%) were males; mean age was 41 ±13; median CD4 count was 23.5 cells/μl (IQR: 8-54.5). The number of patients with positive Mp1p, GM and CrAg tests were 46 (19.5%), 38 (16.1%), and 8 (3.4%), respectively. Mp1p and GM positivity were associated with having symptoms and a CD4 count ≤50 cells/μl (P < 0.05), while CrAg positivity was not (P≥0.05) . Over a mean of 9 months of follow up, 43/44 (97.7%) Mp1p-positive and 30/38 (79.0%) GM-positive patients had culture-confirmed talaromycosis, and 5/8 (62.5%) CrAg-positive patients had culture-confirmed cryptococcosis. Meanwhile, 6/131 (4.6%) Mp1p-negative and 19/137 (13.9%) GM-negative patients had talaromycosis, and 0/186 CrAg-negative patients had cryptococcosis. The sensitivity, specificity, positive predictive value, and negative predictive value for each test are included in the Table. The mortality of cases was higher in Mp1p- or CrAg-positive patients (13.0% and 37.5%) than Mp1p- or CrAg-negative patients (4.7% and 5.3%) at one year follow-up (Chi Square P < 0.05). However, the difference in mortality between GM-positive and GM-negative patients was not statistically significant (P≥0.05). Conclusion: Talaromycosis is significantly more prevalent than cryptococcosis in patients with advanced HIV disease in southern China. Our data demonstrate that the Mp1p EIA and CrAg test are useful tools for rapid diagnose and screening for these infections and should be implemented to reduce HIV morbidity and mortality in southern China. Radha Rajasingham 1 , David Meya 2 , Elizabeth Nalintya 2 , Bruce Larson 3 , David R. Boulware 1 1 University of Minnesota, Minneapolis, MN, USA, 2 Infectious Disease Institute, Kampala, Uganda, 3 Boston University, Boston, MA, USA Background: Screening for cryptococcal antigen (CrAg) among those with advanced HIV disease and treating asymptomatic CrAg+ with fluconazole is lifesaving. However, fluconazole monotherapy still results in 25%mortality.1 Enhanced preemptive treatment options are being evaluated to prevent cryptococcal meningitis. Single dose Ambisome (at 10mg/kg) plus fluconazole is being prospectively evaluated for preemptive treatment in asymptomatic CrAg+. We sought to explore the threshold of efficacy and cost that would improve on current standard of care therapy in Uganda and South Africa, representing a low income setting and a middle income setting respectively. The current price of Ambisome in South Africa is $165 per vial. The anticipated discounted price for treatment of cryptococcal meningitis in resource-limited settings is $16.25 per vial. Methods: We used a decision analytic model to evaluate CrAg screening and treatment outcomes in Uganda for those with a CD4<100 cells/µL. Costs were estimated for screening, preemptive therapy, hospitalization, and maintenance therapy. Parameter assumptions were taken from large prospective CrAg screening studies in Uganda, and clinical trials from sub Saharan Africa.2 CrAg-positive persons could be: a) asymptomatic and thus eligible for preemptive treatment with fluconazole; or b) symptomatic with meningitis with hospitalization. We varied parameters to approximate South African CrAg prevalence and hospitalization costs. Results: At a discounted price of $16.25 per vial, assuming 95% efficacy, Ambisome would be cost-saving to the Ugandan national healthcare system, primarily in meningitis hospitalization costs averted. At the same cost, but assuming 85% efficacy, the cost is $195 to save one life. In South Africa, at the current price of $165 per vial, if assumed to have 95% efficacy, the cost is $3090 to prevent one death from cryptococcal meningitis. At the same price, but assuming 85% efficacy, it would cost $4817 to prevent one death (Figure). If

Poster Abstracts

707 THE COST-EFFECTIVENESS OF AMBISOME FOR ASYMPTOMATIC CRYPTOCOCCAL INFECTION

CROI 2019 271