Immunological failure of first-line and switch to second-line antiretroviral therapy among HIV-infected persons in Tanzania: Analysis of routinely collected national data

Fiona M. Vanobberghen, Bonita Kilama, Alison Wringe, Angela Ramadhani, Basia Zaba, Donan Mmbando and Jim Todd
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Rates of first-line treatment failure and switches to second-line therapy are key indicators for national HIV programs. We assessed immunological treatment failure defined by WHO criteria in the Tanzanian national HIV program.


We included adults initiating first-line therapy in 2004-2011 with a pre-treatment CD4 count, and ≥6 months’ follow-up. We assessed sub-hazard ratios for immunological treatment failure, and subsequent switch to second-line therapy, using competing risks methods to account for deaths.


Of 121,308 adults, 7% experienced immunological treatment failure, and 2% died without observed immunological treatment failure, over a median 1.7 years. The six-year cumulative probability of immunological treatment failure was 19.0% (95% CI 18.5,19.7) and of death, 5.1% (4.8,5.4). Immunological treatment failure predictors included earlier year of treatment initiation (p<0.001), initiation in lower-level facilities (SHR=2.23 [2.03,2.45] for dispensaries versus hospitals), being male (1.27 [1.19,1.33]) and initiation at low or high CD4 counts (for example, 1.78 [1.65,1.92] and 5.33 [4.65,6.10] for <50 and ≥500 versus 200-349 cells/mm3, respectively). Of 7,382 participants in the time-to-switch analysis, 6% switched and 5% died before switching. Four years after immunological treatment failure, the cumulative probability of switching was 7.3% (6.6,8.0) and of death, 6.8% (6.0,7.6). Those who immunologically failed in dispensaries, health centers and government facilities were least likely to switch.


Immunological treatment failure rates and unmet need for second-line therapy are high in Tanzania; virological monitoring, at least for persons with immunological treatment failure, is required to minimize unnecessary switches to second-line therapy. Lower-level government health facilities need more support to reduce treatment failure rates and improve second-line therapy uptake to sustain the benefits of increased coverage.