Nevirapine-based antiretroviral therapy started early in the course of tuberculosis treatment in adult Malawians.
BACKGROUND
The tuberculosis (TB) mortality rate of registered TB patients in Malawi is 23%, and 59% of the deaths occur in the first 2 months of treatment. HIV-related complications appear to be an important cause. Starting antiretroviral therapy early during tuberculosis treatment may improve outcome but problems often arise with drug interactions, adherence, toxicity and immune reconstitution disease (IRD).


METHODS
We prospectively followed 27 HIV-infected adult Malawians after starting Triomune (a generic fixed drug combination of stavudine, lamivudine and nevirapine) in the second week of tuberculosis treatment.


RESULTS
At baseline, 88% had CD4+ T-cell counts <100 cells/ml, all were anaemic and 78% were malnourished. Five patients (19%) died, two withdrew consent and one stopped all drugs due to hepatitis. At 6 months, all but one of the 19 remaining patients had good virological results (16 patients: <400 copies/ml, two patients: <1,000 copies/ml) and the median CD4+ T cell increase was 170 cells/ml. Adverse events were numerous, particularly in the first 2 months. Suspected IRD episodes could be managed without treatment interruptions. During the lead-in phase, 59% of nevirapine plasma levels were sub-therapeutic despite good adherence, compared with only 14% during weeks 4 and 8.


CONCLUSIONS
It is feasible to start Triomune early during TB treatment with good treatment outcome. The nevirapine lead-in phase should be avoided when rifampicin-based tuberculosis treatment is started >1 week beforehand.
van Oosterhout
Joep J G
JJ
University of Malawi College of Medicine, Department of Medicine, Malawi. vanoosterhout@malawi.net
Kumwenda
Johnstone J
JJ
Beadsworth
Michael
M
Mateyu
Gabriel
G
Longwe
Temba
T
Burger
David M
DM
Zijlstra
Eduard E
EE
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000382:microbiology; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D008295:Malawi; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D012293:Rifampin / Q000008:administration & dosage* / Q000627:therapeutic use; D018119:Stavudine / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy
D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine; D012293:Rifampin