Expanded access to HIV treatment achieves big falls in mortality rates in China

Mortality rates fell sharply among people receiving antiretroviral therapy in China between 2003 and 2009, investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes. Overall, people were about 30% less likely to die in the period 2008-09 compared to 2003-04. However, mortality rates were still well in excess of those seen in the general Chinese population.

“The observed mortality rate in this study population (6 deaths/100 person-years) was higher in comparison to results from resource wealthy areas of the world (1 death/100 person-years), but lower than that observed in Sub-Saharan Africa (8 deaths/100 person-years,” comment the authors. “The overall excess mortality we observed was similar to estimates from Sub-Saharan Africa.”

With the right treatment and care, the life expectancy of people with HIV can approach or even equal that of HIV-negative individuals.

A number of studies have analysed the impact of antiretroviral therapy on the prognosis of people receiving care in rich countries and in southern Africa. However, relatively little is known about mortality among people treated with anti-HIV drugs in China.

Since 2002, HIV-positive people in China have had access to HIV treatment through the National Free Antiretroviral Treatment Program (NFATP). As of 2009, over 80,000 patients had received therapy via this programme.

Investigators compared mortality rates between HIV-positive people receiving treatment through NFATP to those observed in the general Chinese population, as matched for age, sex and area of residence (rural vs urban). They also estimated the excess mortality ratios associated with HIV infection and examined the factors associated with excess mortality.

The study population comprised people who received free antiretroviral through NFATP between 2003 and 2009. Between 2003 and 2008, people were eligible for therapy if their CD4 cell count was below 200 cells/mm³. After that date, the CD4 threshold for initiating treatment was increased to 350 cells/mm³. Throughout the study, patients with serious HIV-related symptoms or illnesses could access treatment.

Excess mortality rates were calculated as the difference between deaths observed in the study population and that expected in the matched general population.  

A total of 64,836 participants started treatment through the programme during the study period, with almost half (47%) initiating therapy in 2008-09. The median age of patients at the time treatment was initiated was 38 years, 40% were women and 70% lived in rural areas.

However, the characteristics of people starting antiretrovirals changed considerably over the course of the study. For instance, in 2003-04, 95% of individuals had been infected with HIV via contaminated blood products, but this had decreased to just 18% by 2008-09.

In 2003-04, participants had a median CD4 cell count of 223 cells/mm³ when they started treatment. Even though the CD4 threshold for treatment eligibility was increased to 350 cells/mm³ in 2008, the median CD4 cell count of people starting treatment in 2008-09 had fallen to 141 cells/mm³.

Participants were followed for a median of 1.5 years and contributed a total of 135,509 person-years of follow-up.

During the study period, 8577 (13%) people died, an overall mortality rate of 6.3 deaths per 100 person-years. The mortality rate fell from 9.5 deaths per 100 person-years in 2003-04 to 5.6 deaths per 100 person-years in 2008-09.

However, participants had consistently higher mortality rates than those seen in the general matched population.

The overall excess mortality rate in people with HIV was 6 deaths per 100 person-years. Nevertheless, the excess mortality rate improved over the study period, falling from 9.1 deaths per 100 person-years in 2003-04 to 5.2 deaths per 100 person-years in 2008-09.

The investigators calculated that the standardised mortality ratio – the ratio of observed number of deaths in the study population to that expected in matched population – was 20.1. This fell from 30.8 at the start of the study to 17.0 at its end.

People starting therapy in 2003-04 had a risk of death that was almost 30% higher compared to participants starting treatment in 2008-09 (eHR = 1.27; 95% CI, 1.11-1.45).

Participants who were older when they started therapy had an increased risk of death compared to younger people (over 45 years vs 18 to 28, eHR = 1.63; 95% CI, 1.47-1.82).

The investigators’ calculations also showed the importance of the prompt initiation of therapy. Excess mortality was almost ten times higher among people who had a CD4 cell count of 50 cells/mm³ when they started treatment compared to participants with a CD4 cell count of 350 cells/mm³ or above (eHR = 9.92; 95% CI, 8.59-11.44).

“Among HIV-infected patients receiving cART [combination antiretroviral therapy] through the Chinese NFATP we observed substantial decreases in excess mortality in comparison with the general Chinese population between 2003 to 2009,” conclude the authors. “Further reductions will likely be achieved as NFATP is able to provide more efficacious first and second line cART regimens. Our results indicate further reductions in mortality will follow if patients are identified earlier after HIV infection and are successfully linked with care.”