Starting treatment for both HIV and tuberculosis at the same time lowers the risk of death by around 65%, in comparison with deferring HIV treatment for at least three months, report Spanish investigators in the February 1 edition of Journal of Acquired Immune Deficiency Syndromes. The finding adds evidence to the current debate around co-treatment of the two infections.
In people co-infected with HIV and active tuberculosis (TB), treatment of the TB infection is a priority. However, questions remain as when to start HIV therapy. The main argument for early treatment is the risk of HIV disease progression. Arguments for delayed treatment include the risk of immune reconstitution inflammatory syndrome, interactions between anti-HIV and anti-TB drugs and the large number of pills people need to take when they are taking both treatments together. Current WHO guidelines recommend early treatment in people with low CD4 cell counts and delayed treatment for those with stronger immune systems.
While several prospective studies addressing the question of treatment start timing are ongoing (see here for further details), a group of Spanish investigators undertook a retrospective cohort data analysis of the COMESEM cohort, a database comprising information from almost 7000 HIV-positive people treated in five hospitals in Madrid.
For the analysis, 313 records of HIV/TB co-infection were extracted from the database. Investigators calculated survival in this cohort and then identified factors associated with survival. They collected data on clinical measures and also classified the records according to the timing of anti-TB and anti-HIV therapies: simultaneous treatment, for those who started HIV therapy within two months of starting TB therapy, and deferred treatment, for those who started HIV therapy at least three months after TB therapy.
Within the group, 140 (45%) of people received simultaneous treatment. The only difference between the simultaneous and deferred groups was a significantly lower viral load in those receiving simultaneous treatment than in those receiving deferred treatment (median 63,000 versus 130,000 copies/ml, respectively, p = 0.01). However, the investigators noted that other authors have reported an absence of correlation between basal viral load and survival in TB/HIV co-infection, and at study end no differences in viral load or CD4 cell counts were noted between the groups.
When investigators analysed for factors associated with survival they found that patients who died were more likely to have received deferred HIV treatment, to be injecting drug users, to have an earlier year of diagnosis of TB and HIV and to have another AIDS-defining illness. Age, sex, type of TB, HIV viral load and CD4 cell count were not associated with death. This contrasted with a 2007 report that found a link between low initial CD4 cell counts and death.
Starting HIV and TB therapy at the same time improved survival with simultaneous treatment being associated with around a 65% decreased chance of death, even with other factors taken into account. The investigators noted that this survival advantage was especially evident early after starting treatment, with simultaneous treatment being associated with an 85% lower risk of death after six months and 67% at twelve months. While interesting, the investigators could not conclude that this was a true benefit of simultaneous treatment and not the result of some unknown confounding effect.
The investigators also acknowledge that data on cause of death was not collected and that non-HIV related causes of death might change the study conclusions. However, they conclude that their findings suggest improved survival by using concomitant TB and HIV therapy that seems independent of other factors such as CD4 cell counts. Further research is warranted, they end.
Velasco M et al. Effect of simultaneous use of highly active antiretroviral therapy on survival of HIV patients with tuberculosis. J Acquir Immune Defic Syndr 50:148- 152, 2009.