ABSTRACT
INTRODUCTION: Lactic acidosis is one of the most serious side effects associated with ART, most commonly associated with stavudine. Clinical features are non-specific and specialist laboratory capabilities are essential to confirm the diagnosis, making under-diagnosis likely in resource-constrained settings. Lighthouse Trust is a tertiary referral ART centre with over 23,500 patients on ART. The adjacent University of North Carolina Project laboratory, also serving Kamuzu Central Hospital, has been the only site processing lactate tests in Central Zone for many years. Our objective was to quantify the true incidence within our cohort, and estimate the likely degree of historical missed diagnoses from less central ART clinics. METHODS: All high lactate results between June 2010 and June 2013 were treated as cases, and cross referenced with the Lighthouse database. Patients transferring in to Lighthouse within one month prior to diagnosis were assumed to have been referred due to their lactic acidosis, and moved to the Central Zone cohort to avoid referral bias. Routinely collected quarterly ART cohort data for both Lighthouse and the entire Central Zone were analyzed. RESULTS: Over the three-year period, from within the Lighthouse cohort, there were 138 cases: 74% were female, median duration on ART was 14 months (IQR 10-26), and 98.5% were attributable to stavudine (only two cases to zidovudine). Over this period, the average number of patients taking stavudine at Lighthouse was 10,960 (3,600 on zidovudine). For the whole Central Zone (minus Lighthouse patients) there were 61,000 on stavudine (4,830 on zidovudine), yet only 124 cases of lactic acidosis were apparently diagnosed from within this cohort. CONCLUSIONS: Although cases may, of course, also have been missed at Lighthouse, as a tertiary referral centre the rate observed is likely to be closer to the true incidence. Over the three years, with 138 cases from the 10,960 patients taking stavudine at Lighthouse, it is likely that somewhere in the region of 700 additional cases occurred amongst the 61,000 patients elsewhere in the Central Zone. This equates to somewhere in the region of 550 missed diagnoses or 80% of all cases. Given that the clinical sequelae of undiagnosed lactic acidosis are either death or at best ART default, this provides further vindication for the decision to phase out stavudine in Malawi.
ABSTRACT
BACKGROUND: In July 2011, the Malawi national HIV program implemented the integrated antiretroviral therapy (ART) and prevention of mother-to-child transmission (PMTCT) guidelines. Among the principle goals of the guidelines were increasing ART uptake among TB/HIV co-infected patients and treating TB/HIV patients with a different drug regimen. We, therefore, assessed the effects of the new guidelines on ART uptake, the factors associated with ART uptake and the frequency of ARV-related adverse events in TB/HIV co-infected patients. METHODS: This was an observational cohort study using routine program data. All ART-naïve adult TB/HIV co-infected patients starting TB treatment over the six months preceding and following implementation of 2011 integrated ART/PMTCT guidelines were included. RESULTS: A total of 685 adult TB/HIV co-infected patients were registered in the study; 377 (55%) before and 308 (45%) after the implementation of the new guidelines. ART uptake increased from 70% (240/308) before implementation of the new guidelines to 78% (262/377) after the inception of the new guidelines (P=0.013). The proportion of TB patients initiating ART within two weeks of starting TB treatment increased from 30% before implementation of the new guidelines to 46% after implementation of the new guidelines (p <0.001). The median time from the start of TB treatment to ART initiation dropped from 16 days (IQR 14-31) before the new guidelines to 14 days (IQR 9-20; p = 0.004) after implementing the new guidelines. Factors associated with ART uptake were enrolment in HIV care before starting TB treatment and being a retreatment TB patient. The overall frequency of ARV-related adverse events was higher in patients on d4T/3TC/NVP (35%) than those on TDF/3TC/EFV (25%) but not significantly different (P=0.052). CONCLUSION: Implementation of the 2011 Malawi Integrated ART/PMTCT guidelines was associated with an overall increase in ART uptake among TB/HIV patients and with an increase in the number of patients initiating ART within two weeks of starting their TB treatment. However, the reduction in time between initiating TB treatment and starting ART was small suggesting that further measures must be implemented to facilitate ART uptake. Early enrolment in HIV care provides opportunities for timely ART initiation among TB patients.
