Mortality and causes of death amongst people taking HIV treatment in Senegal examined

A study conducted in Senegal suggests that individuals who die after commencing anti-HIV therapy are most likely to do so in the first year of antiretroviral therapy, largely because antiretroviral therapy was only initiated when they were already very ill because of HIV. The study, published in the May edition of AIDS, also found that mycobacterial infections, particularly tuberculosis (TB), cause a significant number of deaths, and the investigators also speculate that some of the TB-associated deaths could have been caused by immune reconstitution inflammatory syndrome (IRIS).

Senegal initiated an antiretroviral access programme, providing triple drug therapy in 1998 and investigators looked at the survival of 404 individuals who entered this programme between 1998 and 2002. Follow-up data were available until 2005, with the median duration of follow-up being a little short of four years.

Almost all the patients (94%) had symptoms of HIV infection or had progressed to AIDS when they started HIV therapy. Median CD4 cell count was 128 cells/mm³ and median viral load was over 100,000 copies/ml. Only 5% of patients had taken any form of anti-HIV treatment before.

Median CD4 cell count increased by 104 cells/mm³ six months after starting HIV treatment and by 300 cells/mm³ after four years. Median viral load fell by 3 log₁₀/ml six months after the initiation of treatment and did not change substantially thereafter.

A total of 93 individuals died during follow-up, with an overall mortality rate of 6.6 deaths per 100 person years. However, most of these deaths, 47 (with an additional seven patients lost to follow-up and assumed dead), occurred during the first year of anti-HIV therapy, yielding a mortality rate for that year of 12.5 deaths per 100 person years for this year. This fell in the second year to 6.6 deaths per 100 person years and kept falling thereafter (4.5, 2.3, 2.2 deaths per 100 person years in years three, four and five respectively).

The risk of dying during the first year of anti-HIV treatment was associated with CD4 cell count before potent antiretroviral therapy was initiated, with, unsurprisingly, patients with a CD4 cell count below 50 cells/mm³ having the highest risk (18%) and those with a CD4 cell count above 200 cells/mm³ the lowest (6%).

As well as CD4 cell count, the investigators identified a body mass index below 19kg/m² and a haemoglobin level below 10g/dl as being associated with an increased risk of death. It is well known that both of these factors are associated with an increased risk of death.

Attention was then turned to causes of death, which were known for 80 of the 93 patients. Pulmonary TB explained 17 deaths, eight of which occurred in the first year of anti-HIV treatment. The investigators also noted that nine of the patients who died of TB had a history of the infection dating back to before the initiation of HIV therapy, suggesting that the recurrence of TB may have been due to IRIS. Infections of the central nervous system also caused 17 deaths, septicaemia caused eight deaths, with a similar number caused by unspecified disease. In addition, five deaths were caused by liver failure, with hepatitis B infection present in one patient and hepatitis C in another. Side-effects of antiretroviral therapy are thought to have contributed to three deaths, including one case of diabetes, one case of high amylase and a case of lactic acidoisis.

“Efforts towards an earlier initiation of HAART in the course of HIV infection and a better approach to diagnosis and management of tuberculosis and opportunistic infections will be the next step to limit the still too high mortality,” conclude the investigators.