Application of a Multistate Model to Evaluate Visit Burden and Patient Stability to Improve Sustainability of Human Immunodeficiency Virus Treatment in Zambia.

Background: Differentiated service delivery (DSD) for human immunodeficiency virus (HIV)-infected persons who are clinically stable on antiretroviral therapy (ART) has been embraced as a solution to decrease access barriers and improve quality of care. However, successful DSD implementation is dependent on understanding the prevalence, incidence, and durability of clinical stability. Methods: We evaluated visit data in a cohort of HIV-infected adults who made at least 1 visit between 1 March 2013 and 28 February 2015 at 56 clinics in Zambia. We described visit frequency and appointment intervals using conventional stability criteria and used a mixed-effects linear regression model to identify predictors of appointment interval. We developed a multistate model to characterize patient stability over time and calculated incidence rates for transition between states. Results: Overall, 167819 patients made 3418018 post-ART initiation visits between 2004 and 2015. Fifty-four percent of visits were pharmacy refill-only visits, and 24% occurred among patients on ART for >6 months and whose current CD4 was >500 cells/mm3. Median appointment interval at clinician visits was 59 days, and time on ART and current CD4 were not strong predictors of appointment interval. Cumulative incidence of clinical stability was 66.2% at 2 years after enrollment, but transition to instability (31 events per 100 person-years) and lapses in care (41 events per100 person-years) were common. Conclusions: Current facility-based care was characterized by high visit burden due to pharmacy refills and among treatment-experienced patients. Differentiated service delivery models targeted toward stable patients need to be adaptive given that clinical stability was highly transient and lapses in care were common.

Brief Report: Assessing the Association Between Changing NRTIs When Initiating Second-Line ART and Treatment Outcomes.

BACKGROUND: After first-line antiretroviral therapy failure, the importance of change in nucleoside reverse transcriptase inhibitor (NRTI) in second line is uncertain due to the high potency of protease inhibitors used in second line. SETTING: We used clinical data from 6290 adult patients in South Africa and Zambia from the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Southern Africa cohort. METHODS: We included patients who initiated on standard first-line antiretroviral therapy and had evidence of first-line failure. We used propensity score-adjusted Cox proportional-hazards models to evaluate the impact of change in NRTI on second-line failure compared with remaining on the same NRTI in second line. In South Africa, where viral load monitoring was available, treatment failure was defined as 2 consecutive viral loads >1000 copies/mL. In Zambia, it was defined as 2 consecutive CD4 counts <100 cells/mm. RESULTS: Among patients in South Africa initiated on zidovudine (AZT), the adjusted hazard ratio for second-line virologic failure was 0.25 (95% confidence interval: 0.11 to 0.57) for those switching to tenofovir (TDF) vs. remaining on AZT. Among patients in South Africa initiated on TDF, switching to AZT in second line was associated with reduced second-line failure (adjusted hazard ratio = 0.35 [95% confidence interval: 0.13 to 0.96]). In Zambia, where viral load monitoring was not available, results were less conclusive. CONCLUSIONS: Changing NRTI in second line was associated with better clinical outcomes in South Africa. Additional clinical trial research regarding second-line NRTI choices for patients initiated on TDF or with contraindications to specific NRTIs is needed.