Better Retention Rates Observed in Patients on Lopinavir than Atazanavir in Uganda Kate Ssamula, Juan Gonzalez Perez, Jonathan Ikapule, Penninah Iutung AIDS Healthcare Foundation, Kampala Uganda

Background Long-term retention of patients on 2nd line therapy has received relatively little attention in the medical research field There is limited data on failure of 2nd line therapy and the use of third-line ART in people living with HIV in resource-limited settings We have limited access to third line ART in Sub-Saharan Africa so our aim is to make sure we optimize our 2nd line drug options Uganda is one of the countries that lead the way in rapid scale up of ART therefore expecting it to have a considerable number of patients on 2nd line hence the need to determine retention on 2nd line ART.

Objectives To determine the retention of all patients ever initiated on 2nd line therapy To determine factors associated with attrition on 2nd line therapy To determine the proportion of clients on 2nd line that still had viral suppression at the closure of the cohort

Methods

Methods Retrospective cohort study Clients initiated on 2nd line therapy between January 2004 to December 2013 10 health facilities in different parts of Uganda: Urban facilities- 2 in Kampala, Masaka and Soroti Peri-Urban facilities- Kalisizo, Lyantonde Rural facilities- Kakuuto, Gombe, Maddu and Rakai Exclusions: clients initiated on 2nd line therapy for other reasons like; Adverse effects to NNRTIs Drug interactions Pregnancy Clinical trials as a reason for being on 2nd line therapy Children 14 years and below

Methods T0 = Date client was initiated on 2nd line T1= 30th December 2013 Routine monitoring tests were done for all clients who were due: CD4 and VL Outcome status: Attrition while on 2nd line therapy Kaplan-Meier curves were used to estimate the risk of attrition over time and Cox proportional hazard model was used to determine the factors associated with attrition on 2nd line

Definitions An active client was defined as one whose last visit to the facility was within 3 months to the closing date of the cohort A client was considered to be on 2nd line if they had a PI in their current regimen that had replaced a NNRTI and one NRTI had been changed A client was considered as LTFU if they were absent for >90 days after his/her last scheduled appointment

Definitions Retention on 2nd line was defined as a client who was alive and confirmed to be receiving 2nd line therapy as evidenced by the last clinic visit date and drug pick up Attrition referred to a patient who was documented as having died or lost to follow up.

Definitions Clinical failure was defined as a patient presenting with a new or recurrent WHO stage 4 condition Immunological failure was defined as a fall in CD4 count to pre-therapy baseline CD4, persistent CD4 count < 100 cells or 50% fall from the on-treatment known peak value Virological failure was defined as Plasma viral load above 1000 copies/ ml based on two consecutive viral load measurements after 3 months with adherence support

Results

Study participants Number Notes on status 983 (2.2%) Total number of files reviewed out of 44,624 clients -119 = 864 119 clients dropped because of lack of data on 1st line regimen -143 =721 143 dropped due to reason of switching ART regimen not related to failure on 1st line treatment -12 = 709 12 clients dropped due to lack of basic demographic data -29 = 680 29 Clients below the age 15 years were dropped -22 = 658 22 dropped due to lack of confirmed clinical outcome at closure of the cohort 658 Considered in final analysis

Characteristics at T0 Clients on 2nd line after exclusion N=658 Gender Female 353 (53.6%) Median Age in years (IQR) 38 (IQR: 31-45) 1st Line Regimen NVP based 516 (78.4%) EFV based 142 (21.6%) Reasons for switching to 2nd line VF- 286 (43.5%) IF- 284 (43.1%) CF- 88 (13.4%) Median duration on 1st Line, Months (IQR) 28 (11-49) Median CD4 before switch to 2nd line (IQR) 83 (33- 200) Median VL before switch to 2nd line Log 10 (IQR) 5.0 (IQR 4.4- 5.4)

Characteristics at T1 2nd Line Regimen LPV/r -551 (83.7%) ATV/r- 107 (16.3%) Median duration on 2nd Line, Months (IQR) 18 (9-42) Clinical outcome at the end of follow up Active 504 (76.6%) Deceased 99 (15.1%) LTFU 34 (5.2%) Transferred out 21 (3.2%) Median current* CD4 n=566 Median= 324 (IQR: 148-502) Median current* VL (Log 10) n=338 Median= 4.01 (IQR 4.4- 5.36) Clients found to be failing on 2nd line n=338 20 (5.2%) Current CD4 was defined as a patient having done a CD4 count within 6 months to the closure of the cohort.

Results

Results Variable N=658 Rate (/1000 PYRS) HR (95% CI) P value Gender   Female 353 120.6 Male 305 122.9 1.02 (0.71 , 1.46) 0.916  2nd Line Regimen LPV based 551 109.1 ATV based 107 269.7 2.47 (1.55-3.96) <0.001 Reason for switch VF 286 27.0 IF 284 309.6 9.23 (5.21- 16.4) CF 88 58.9 1.59 (0.61- 4.10) 0.339 Other variables included in the model but were not significant were age, NNRTI Regimen, 1st Line Regimen, CD4 count before 2nd line, location of the clinic

Summary and conclusions Overall retention of clients on 2nd line was much better than documented retention studies done in SSA though majority are on 1st line therapy and shorter durations Retention on 2nd line therapy was significantly better in clients taking LPV/r containing regimen even though both PIs are currently recommended 2nd line treatment Patients with immunological failure as a reason for switching to 2nd line had a higher probability of attrition probably because of late detection of treatment failure

Summary and Conclusions Inadequate access to VL monitoring and HIV genotype testing are currently major barriers to optimal management of patients failing second-line ART. Early detection of treatment failure through routine monitoring is necessary if we want to maximize our 2nd line treatment options