Second‐line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline^*

Abstract

Objectives The Malawi antiretroviral therapy (ART) programme uses the public health approach to identify ART failure. Advanced disease progression may occur before switching to second-line ART. We report outcomes for patients evaluated and initiated on second-line treatment in Malawi. Methods Patients meeting Malawi immunological or clinical criteria for ART failure in two large urban ART clinics were evaluated for virological failure (viral load >400 HIV-1 RNA copies/mL) and, if failure was confirmed, initiated on second-line ART (zidovudine/lamivudine/tenofovir/lopinavir/ritonavir). Patients were seen monthly and laboratory evaluations were performed quarterly and as needed. We performed logistic regression modelling to identify factors associated with mortality, mortality or new HIV illnesses, and virological suppression at 12 months. Results Of the 109 patients with confirmed virological failure, five patients died prior to initiation, three declined switching and 101 patients initiated second-line treatment. Over 12 months, 10 additional patients died, 34 patients experienced 45 HIV-related events, and 19 patients experienced grade 3 or 4 toxicities. Among survivors, 85.2% had HIV-1 RNA<400 copies/mL at 12 months. While power to distinguish differences was limited, response rates were similar regardless of baseline resistance level. The median CD4 count increase was 142 cells/μL. World Health Organization clinical failure at baseline [odds ratio (OR) 3.47; 95% confidence interval (CI) 1.14–10.59] and body mass index <18.5 (OR 4.43; 95% CI 1.15–17.12) were risk factors for death. Baseline CD4 count <50 cells/μL was associated with increased risk for death or morbidity at 12 months (OR 2.57; 95% CI 1.01–6.52). Conclusions Second-line treatment in Malawi was associated with substantial mortality, morbidity and toxicity but, among survivors, virological outcomes were favourable.

Accumulation of HIV Drug Resistance Mutations in Patients Failing First-Line Antiretroviral Treatment in South Africa

“…22 A study from Malawi has shown a high rate (85%) of virological suppression on second-line ART despite extensive NRTI resistance. 23 In our study, over half of the patients, including those with complex DRMs, achieved virological suppression on second-line ART. Despite these relatively favorable on-treatment outcomes, a study of PI monotherapy after failure of an NNRTI-based regimen revealed a high incidence of low-level viremia.…”

The Prediction of Integrase Inhibitors Efficacy in Third Line Regimen after First and Second Line Antiretroviral Therapy Failure in Senegal

“…Despite the unavailability of VL in remote areas in Senegal, HIV-1 infected patients were followed using VL testing in the main site in the capital city. Our results shows a high rate of VF (82.7%) during the first line ART as previously described in Nigeria [13], which was the main reason for switching of line regimen [14,15]. However, our data showed nine patients switched to second line regimen with three without VL testing and six with plasma viral load below 3 log 10 copies/ml.…”

Monitoring Antiretroviral Therapy in Resource-Limited Settings: Balancing Clinical Care, Technology, and Human Resources

“…Nonetheless, responses to second-line therapy in RLS have been favorable to date, with approximately 78% to 88% of second-line initiators alive and on treatment at the end of 1 year [19,22,33]. Even in the Malawian setting with high-level NRTI resistance, virologic suppression rates were 70% overall and exceeded 85% among survivors at the end of 1 year on second-line therapy [22]; long-term follow-up of this cohort has not yet been reported. Such favorable response is likely due to the potency of boosted protease inhibitors that have shown substantial activity among protease inhibitor-naïve patients, even as monotherapy [34][35][36][37].…”

“…Risk factors for death included being identified as clinical failure or having a body mass index <18.5. Likewise, having CD4 count <50 cells/µL was associated with increased risk for death or AIDS progression [22].…”