Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.
BACKGROUND
In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia.


METHODS
Multicohort study of 17 ART programmes. All sites monitored CD4 cell count and had access to second-line ART and 10 sites monitored viral load. We compared times to switching, CD4 cell counts at switching and obtained adjusted hazard ratios for switching (aHRs) with 95% confidence intervals (CIs) from random-effects Weibull models.


RESULTS
A total of 20 113 patients, including 6369 (31.7%) patients from 10 programmes with access to viral load monitoring, were analysed; 576 patients (2.9%) switched. Low CD4 cell counts at ART initiation were associated with switching in all programmes. Median time to switching was 16.3 months [interquartile range (IQR) 10.1-26.6] in programmes with viral load monitoring and 21.8 months (IQR 14.0-21.8) in programmes without viral load monitoring (P < 0.001). Median CD4 cell counts at switching were 161 cells/microl (IQR 77-265) in programmes with viral load monitoring and 102 cells/microl (44-181) in programmes without viral load monitoring (P < 0.001). Switching was more common in programmes with viral load monitoring during months 7-18 after starting ART (aHR 1.38; 95% CI 0.97-1.98), similar during months 19-30 (aHR 0.97; 95% CI 0.58-1.60) and less common during months 31-42 (aHR 0.29; 95% CI 0.11-0.79).


CONCLUSIONS
In resource-limited settings, switching to second-line regimens tends to occur earlier and at higher CD4 cell counts in ART programmes with viral load monitoring compared with programmes without viral load monitoring.
Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
Keiser
Olivia
O
Tweya
Hannock
H
Boulle
Andrew
A
Braitstein
Paula
P
Schecter
Mauro
M
Brinkhof
Martin W G
MW
Dabis
François
F
Tuboi
Suely
S
Sprinz
Eduardo
E
Pujades-Rodriguez
Mar
M
Calmy
Alexandra
A
Kumarasamy
Nagalingeswaran
N
Nash
Denis
D
Jahn
Andreas
A
MacPhail
Patrick
P
Lüthy
Ruedi
R
Wood
Robin
R
Egger
Matthias
M
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D018791:CD4 Lymphocyte Count; D003906:Developing Countries; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008507:Medically Underserved Area; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors