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Regimen Durability and Tolerability to 36-month Duration on ART in Khayelitsha, South Africa
Andrew Boulle*1, G Van Cutsem2, D Coetzee1, K Hilderbrand1,2, E Goemaere2, and G Maartens3
1Univ of Cape Town, Sch of Publ Hlth and Family Med, South Africa; 2Médecins Sans Frontières; and 3Univ of Cape Town, South Africa
Background: ART began in
Khayelitsha in May 2001, and by the end of 2004, more than 1700 treatment-naïve
adults had started ART. The initial drug regimens comprised a zidovudine/lamivudine
(AZT/3TC) nucleoside reverse transcriptase inhibitor (NRTI)-backbone combined
with either nevirapine (NVP) or efavirenz (EFV). With time, EFV use
predominated, and later the first-line regimen changed to stavudine/lamivudine/nevirapine
(d4T/3TC/NVP).
Methods: This was a prospective cohort
study, with all individual ART drug stops coded by cause, and follow-up extending
until the end of June 2005. Data were analyzed using survival analysis of time
to switch by exposure to each individual ART drug, broken down by cause of
switch. Virological failure analyzed as time to second consecutive value above
5000 copies/mL in line with local protocols for virological failure.
Results: A preliminary analysis with
follow-up extending until the end of 2004 revealed that cumulatively 11.9% (95%CI 7.6 to
18.4) of patients had been
switched to second-line by 36 months on ART, fewer than would be anticipated
based on the viral load results (figure 1). By 24 months on ART, similar
proportions of patients had changed from d4T, AZT, and NVP because of toxicity
(8.5%, 8.7%, and 8.9%, respectively; figure 2). For patients on d4T, the rate
of switching due to symptomatic hyperlactatemia or lactic acidosis was 15 of 1000
patient-years (95%CI 9 to 31), and 17 of 1000 person-years (95%CI 8 to 29 ) due
to peripheral neuropathy. Of 44 switches, 36 were attributable to anemia in
patients on AZT. Raised transaminases were a more frequent cause of
toxicity-driven switches compared with rash in patients on NVP. Overall, 59% of
patients remained on their initial regimen at 36 months’ duration on ART.
Figure 1. Switches to second-line and
confirmed
viral rebound.
Figure 2. Switches due to toxicity by
exposure to each drug.
Conclusions: The substitution of AZT with d4T in the
first-line regimen has resulted in fewer regimen changes due to anemia or
neutropenia, and correspondingly a higher proportion of changes due to
peripheral neuropathy and lactic acidosis. The incidence of symptomatic
hyperlactatemia or lactic acidosis is higher in this cohort than that anticipated
from the literature. There is generally a clinical delay in switching to
second-line compared with the point that virological failure is confirmed on
laboratory criteria. The Khayelitsha cohort provides an opportunity to reliably
explore regimen durability and tolerability to 36 months in the context of treatment
in a developing country.
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