Early HIV treatment, combined with therapy to prevent tuberculosis, sharply reduced morbidity in a randomised trial in Africa, a researcher said. The effects of the two forms of treatment were independent but highly statistically significant, according to Dr Christine Danel, of the University of Bordeaux in France.
And even when patients had a relatively robust immune system, the combined approach reduced the risk of such things as all-cause mortality, Aids-defining events, and bacterial diseases, Danel reported in MedPage Today.
The findings come from a large, randomised trial in Côte d’Ivoire and suggest that early antiretroviral treatment (ART) and TB prophylaxis should be the standard of care in the region. “Severe morbidity is reduced by early ART and by isoniazid preventive therapy given for 6 months,” Danel said.
Successive guidelines from the World Health Organisation (WHO) have slowly lowered the bar for HIV treatment, Danel noted – by raising the treatment threshold CD4 T-cell count from below 200 per cubic millimetre in 2006 to below 500 in 2013. But the question, she said, is should treatment start even earlier, when the CD4 cell count is still higher. The WHO also recommends 6 months of preventive TB therapy with isoniazid for people with HIV, but many countries don’t follow the guideline because they fear missing an active case of TB and creating resistance.
To study the issue, Danel and colleagues enrolled 2,076 people with HIV in a multicentre randomised, controlled trial with a 2×2 factorial design between March 2008 and July 2012. Importantly, patients had a CD4 count of less than 800 but were not eligible for HIV treatment under whatever WHO guidelines were applicable at the time of enrollment. They were assigned to start HIV therapy either immediately on enrollment or to wait until they met the applicable WHO guidelines. Within those groups, patients were assigned to get HIV treatment alone or with 6 months of concomitant isoniazid at 300 milligrams a day.
The primary endpoint of the study was the proportion of patients in each arm with severe HIV morbidity, defined as all-cause mortality, any Aids defining-event, severe bacterial diseases, and non-Aids cancers. All patients were treated with tenofovir/emtricitabine (Truvada) combined with one of three other antiretroviral drugs — efavirenz (Sustiva), lopinavir/ritonavir (Kaletra), or zidovudine (AZT).
After a median follow-up of 30 months, Danel reported, it was clear that patients who started ART early did better as did those on isoniazid, and the effects were independent. Specifically, among patients treated according to WHO guidelines the proportion with severe morbidity reached 11.4%, compared with 6.6% among those getting immediate treatment; the difference yielded an adjusted hazard ratio for morbidity of 0.56 in favor of early treatment (P=0.0002); similarly, among patients not getting isoniazid the proportion with severe morbidity was 10.7%, compared with 7.2% among those who got the drug; and the difference yielded an adjusted hazard ratio for morbidity of 0.65 in favour of early treatment, (P=0.005).
All told, there were 204 episodes of severe morbidity including 47 deaths, with descending numbers depending on treatment arm – 75 incidents and 16 deaths among those getting ART alone according to WHO guidelines, followed by 60 events and 10 deaths among those also getting isoniazid, 41 events and 13 deaths among those getting just early ART, and 28 events and eight deaths in the group getting both early ART and isoniazid. Most of the events were either TB or other bacterial diseases, Danel reported.