Iman Wanis and Philippa Easterbrook World Health Organization, HIV Department (ATC) Geneva, Switzerland July 2011 What is the reality in the field? Survey of access to drugs and diagnostics

Survey methodology 19 persons from Asia, Africa Most seeing >100 patients/year Semi-structured telephone interview  Uganda (4 physicians, and 1 lab manager)  Malawi (2 physicians)  Botswana (1 physician)  Laos (1 MOH)  Vietnam (1 physician)  South Africa (3 physicians, and 1 microbiologist)  Ethiopia (1 pharmacist)  Cambodia (1 physician MSF)  Thailand (1 physician)  India (1 physician)  CIPLA CEO

Perspectives on epidemiology/burden No of cases per year  Pietermaritzburg:  Kampala: 750  Malawi: 2000  Laos: 100 (25 at 4 sites) Declining incidence (Thailand, Botswana) Seasonal peak in rainy season (Uganda) IRIS 30-50% unmasking (S. Africa and Uganda) 30% (Thailand) 75% pre-ART; <5% unmasking (Malawi)

Mortality Source: Govender et al, CROI 2010 Source: Bahr et al 2011, ICCC 2011 Impact of introduction of routine K+ supplementation : COAT Trial, Uganda Case fatality rates remain high despite increasing access to Amphotericin B Reasons for persistent high fatality: 1.Late presentation with advanced HIV and advanced CM/ severe neurological impairment In South Africa (2005-8), 81% of 3132 patients had CD4 <100 cells/ml (Govender et al, CROI 2010) 2. Amphotericin B toxicity (COAT trial) Trends in Treatment of Adults with Incident Cryptococcosis, South Africa,

Diagnostics Different diagnostic approaches, esp. in SSA  CSF India ink only  CSF India ink and CRAG simultaneously  CSF CRAG only on India Ink negative (S. Africa, Botswana)  Culture only in few sites Significant variation in approach to CRAG funding  Global Fund (Laos), PEPFAR, NGOs (MSF) (Malawi), government only if preceeding HIV +ve diagnosis (Uganda) Screening not seen as high priority  Thailand has now introduced  Botswana now under discussion Wide variation in access to CRAG esp. in SSA (India ink in 75% of labs in Uganda 2007)  Only in main city hospitals or private sector  Research studies

Amphotericin B Wide variation in access to amphotericin B, esp. in SSA  Generally main city hospitals only Drug stock-outs a problem  Poor forecasting, and distribution  International shortage at present Wide variation in availability of generic amphotericin B  4 generic companies in India  Few or none in SSA  90% reduction in price of liposomal ampho negotiated with MSF and WHO for treatment of visceral leishmaniasis Significant variation in approaches to funding of amphotericin B  Global Fund (Laos)  PEPFAR (selected sites in Uganda)  NGOs (MSF)  National government (Asia, Botswana, South Africa)  UNITAID donation  Self-pay (less than half of patients can afford in Uganda)

Fluconazole Perception that associated with higher mortality Free through Pfizer donation Increasingly used as first line in absence of amphotericin B Higher doses starting to be used; no problems reported  Malawi: 800mg 2w then 600mg  Uganda: 1200mg for 2 w then 400mg 8w Often fluconazole not available, even in cities – no clear reason

Flucytosine No registration or availability in any SSA, despite inclusion in several national guidelines Limited number of manufacturers Very high cost $3.22 per tablet, about $ per day

Monitoring Wide variation in monitoring practice and funding source for tests e.g. Uganda self-pay  No monitoring of ICP; manometers rarely available  Very limited toxicity monitoring (Malawi)  SOPs (Botswana)  K+, creat., CBC (Day 1, 7 and 14) (Laos)  Baseline Hb and after 7 days, Electrolytes and LFTs after 4 days (Uganda), or every 2-3 days Wide variation in funding source for tests  Uganda self-pay  National government (Laos, South Africa) Delays in receiving results Use of pre-emptive fluid load and K replacement only in few settings

What they would like to see? 1 Free/low cost diagnosis, Rx and monitoring Ready access to rapid low cost diagnostics (in serum and CSF) to allow earlier diagnosis  Good drugs given late will not impact on prognosis  Enthusiasm for LFA  Screening not yet indicated Simplified treatment and need for cost-effectiveness comparisons that factor in monitoring and toxicity management Short course ampho without need for blood test monitoring High dose oral fluconazole vs. ampho Addition of 5FC to fluconazole to reduce risk of relapse (no 5FC in SSA)

What they would like to see 2 Better treatment access  Several Amb generics in Asia, but not in SSA  No access to 5FC in SSA and costly  PSM needs improvement Improved referral pathways of Crypto patients for ART Need for guidance on management of non-responders and late relapses Need to analyse data from Diflucam partnership – wealth of data