Diagnosis of antiretroviral therapy failure in Malawi: poor performance of clinical and immunological WHO criteria

Objectives  In antiretroviral therapy (ART) scale-up programmes in sub-Saharan Africa viral load monitoring is not recommended. We wanted to study the impact of only using clinical and immunological monitoring on the diagnosis of virological ART failure under routine circumstances.
Methods  Clinicians in two urban ART clinics in Malawi used clinical and immunological monitoring to identify adult patients for switching to second-line ART. If patients met clinical and/or immunological failure criteria of WHO guidelines and had a viral load <400 copies/ml there was misclassification of virological ART failure.
Results  Between January 2006 and July 2007, we identified 155 patients with WHO criteria for immunological and/or clinical failure. Virological ART failure had been misclassified in 66 (43%) patients. Misclassification was significantly higher in patients meeting clinical failure criteria (57%) than in those with immunological criteria (30%). On multivariate analysis, misclassification was associated with being on ART <2 years [OR = 7.42 (2.63, 20.95)] and CD4 > 200 cells/μl [OR = 5.03 (2.05, 12.34)]. Active tuberculosis and Kaposi's sarcoma were the most common conditions causing misclassification of virological ART failure.
Conclusion  Misclassification of virological ART failure occurs frequently using WHO clinical and immunological criteria of ART failure for poor settings. A viral load test confirming virological ART failure is therefore advised to avoid unnecessary switching to second-line regimens.     

Practices to improve identification of adult antiretroviral therapy failure at the Lighthouse Trust clinic in Lilongwe, Malawi

Objectives Evaluating treatment failure is critical when deciding to modify antiretroviral therapy (ART). Virologic Assessment Forms (VAFs) were implemented in July 2008 as a prerequisite for ordering viral load. The form requires assessment of clinical and immunologic status. Methods Using the Electronic Medical Record (EMR), we retrospectively evaluated patients who met 2006 WHO guidelines for immunologic failure (≥15 years old; on ART ≥6 months; CD4 count 50% drop from peak OR CD4 persistently <100 cells) at the Lighthouse Trust clinic from December 2007 to December 2009. We compared virologic screening, VAF implementation and ART modification during the same period using Fisher’s exact tests and unpaired t‐tests as appropriate. Results Of 7000 enrolled ART patients ≥15 years old with at least two CD4 counts, 10% had immunologic failure with a median follow‐up time on ART of 1.4 years (IQR: 0.8–2.3). Forty (6%) viral loads were ordered: 14 (35%) were detectable (>400 HIV RNA copies/mL) and one (7%) patient was switched to second‐line therapy. Overall, 259 VAFs were completed: 67% for immunologic failure and 33% for WHO Stage 4 condition. Before VAF implementation, 1% of patients had viral loads drawn during routine care, whereas afterwards, 8% did (P < 0.0001; 95% CI: 0.03–0.08). Conclusions Clinicians did not identify a large proportion of immunologic failure patients for screening. Implementation of VAFs produced little improvement in virologic screening during routine care. Better training and monitoring systems are needed.     

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

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.