Background: As access to and duration of antiretroviral therapy (ART) increase, the number of patients experiencing first-line ART failure, followed by the need for second-line treatment is rising. The availability of second-line ART drugs is, however, often insufficient in resource-limited settings. For this reason many patients remain on a failing first-line regimen instead of being given more efficient second-line treatment. The long-term consequences and outcomes of this practice in rural areas are uncertain. In rural Tanzania, we have therefore studied the clinical and immunological development of adults and adolescents after virological failure, both those remaining on first-line-, and those being switched to second-line ART.
Methods: 44 adults (≥15 years) who had been on ART for at least six months and had a confirmed virological failure (HIV-1 RNA ≥400 copies/mL) were included in the study. In the period December 2006 – September 2009, 27 patients (61 %), continued first-line ART, while 17 patients (39 %), changed to second-line ART because of a failing first-line regimen. Follow-up data was collected through February 2010. Data on clinical, immunological and virological outcomes for the two groups was compared and analysed by logistic regression analyses and paired samples T-tests.
Results: At the time of virological failure the median viral load (VL) was 28 000 copies/mL (IQR 2630-149 000) and the mean CD4 cell count was 321.2 cells/µL, standard deviation (SD) 224.88. At the same time samples from 33 patients were available for drug resistance testing, out of which 20 (60.6 %) had detectable resistance. Six patients died following virological failure, but there was no significant difference in the odds of death between patients on first-line ART compared to those on second-line ART, Odds Ratio 0.58; P = 0.54. The mean changes in CD4 cell count 6, 12 or 18 months after virological failure was -28.6, -80.5 and -48.3 cells/µL for those on first-line ART, while the mean changes was + 56.2, +83.2 and +90.9 cells/µL for those on second-line ART.
Conclusion: Patients who remained on a failing first-line regimen had a declining CD4 cell count and were at risk of opportunistic infections and death. Patients who changed to second-line ART had an increasing CD4 cell count. They were still at risk of opportunistic disease and death, which could be explained by late detection of virological failure. Improved access to VL monitoring and second-line ART could improve prognosis for HIV-infected patients in rural settings.