Early clinical and programmatic outcomes with tenofovir-based antiretroviral therapy in Zambia.
BACKGROUND
In July 2007, amid some controversy over cost, Zambia was the first African country to introduce tenofovir (TDF) as a component of first-line antiretroviral therapy (ART) on a wide scale.


METHODS
We compared drug substitutions, mortality, and "programmatic failure" among adults starting TDF-, zidovudine (ZDV)-, and stavudine (d4T)-containing ART. Programmatic failure was defined as death, withdrawal, or loss to follow-up.


RESULTS
Between July 2007 and January 2009, 10,485 adults initiated ART (66% on TDF, 23% on ZDV, 11% on d4T), with a median follow-up time of 239 (interquartile range 98, 385) days. Those starting TDF were more likely to be male and more likely to have indicators of severe disease at baseline. In adjusted Cox proportional hazards models, ZDV- (adjusted hazard ratio [AHR] = 2.74, 95% confidence interval [CI] = 2.30-3.28) and d4T-based regimens (AHR = 1.92, 95% CI = 1.55-2.38) were associated with higher risk for drug substitution when compared with TDF-based regimens. Similar hazards were noted for overall mortality (ZDV: AHR = 0 .81, 95% CI = 0.62-1.06; d4T: AHR = 1.03, 95% CI = 0.74-1.43) and programmatic failure (ZDV: AHR = 0.99, 95% CI = 0.88-1.11; d4T: AHR = 1.11, 95% CI = 0.96-1.28) when compared with TDF.


CONCLUSIONS
TDF is associated with similar clinical and programmatic outcomes as ZDV and d4T but appears to be better tolerated. Although further evaluation is needed, these results are encouraging and support Zambia's policy decision.
Chi
Benjamin H
BH
Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu
Mwango
Albert
A
Giganti
Mark
M
Mulenga
Lloyd B
LB
Tambatamba-Chapula
Bushimbwa
B
Reid
Stewart E
SE
Bolton-Moore
Carolyn
C
Chintu
Namwinga
N
Mulenga
Priscilla L
PL
Stringer
Elizabeth M
EM
Sheneberger
Robert
R
Mwaba
Peter
P
Stringer
Jeffrey S A
JS
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir; D016896:Treatment Outcome; D015024:Zambia
D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine