Starting ART immediately after HIV diagnosis cuts mortality risk by two-thirds for people with high CD4 cell counts

People with a high CD4 cell count who start antiretroviral therapy (ART) immediately after diagnosis with HIV cut their 12-month mortality risk by two-thirds, according to research conducted in China and published in Clinical Infectious Diseases.

The retrospective study involved over 35,000 people who were newly diagnosed with HIV between 2012 and 2014. All had a CD4 cell count above 500 cells/mm³. Over 12 months of follow-up, individuals who started antiretrovirals within 30 days of their diagnosis had a 63% reduction in their mortality risk compared to people who remained antiretroviral-naïve. Delayed treatment (initiation after 30 days of diagnosis) also reduced mortality, but only by 26%.

“Our results demonstrate that PLWH [people living with HIV] with a CD4 cell count > 500 cells/mm³ who initiated ART within 30 days of diagnosis…experienced a 63% decrease in mortality,” write the investigators. “Additional risk factors for mortality in this study were older age, being male, having lesser education, and becoming infected via injection drug use or heterosexual contact.”

Since 2015, the World Health Organization has recommended that all people with HIV should take antiretroviral therapy, regardless of CD4 cell count. This is because research has proved that treatment, even at high CD4 cell counts, reduces the risk of illness and death. Moreover, people taking treatment who have an undetectable viral load have an effectively zero risk of transmitting HIV to their sexual partners.

Investigators in China wanted to see if immediate ART cut the mortality risk for people with a high CD4 cell count (above 500 cells/mm³) at the time of their diagnosis. They therefore designed a retrospective study involving approximately 35,500 adults newly diagnosed with HIV between 2012 and 2014. All had a CD4 cell count above 500 cells/mm³ and were followed for 12 months after their diagnosis. Study participants were divided into three groups according to their use of HIV therapy:

• Immediate ART: initiation within 30 days of diagnosis.
• Deferred ART: initiation more than 30 days after diagnosis.
• No ART: no HIV treatment.

The researchers hypothesised that immediate ART would be associated with a reduced risk of mortality.

The participants had a median age of 32 years, 75% were male, 64% had a primary education or less, 39% were married, 60% acquired HIV through heterosexual contact. Median baseline CD4 cell count was 616 cells/mm³.

ART was started within 30 days of diagnosis by 5% of the cohort. A further 16% initiated therapy more than 30 days after diagnosis and the remaining people remained ART naïve.

A total of 790 (2% of the cohort) deaths were documented over 12 months of follow-up, a mortality rate of 2.31 per 100 person-years.

There were 19 deaths in the immediate ART group, a mortality rate of 1.04 per 100 person-years. A total of 58 deaths occurred in the deferred ART group, a mortality rate of 2.25 per 100 person-years. The remaining 713 deaths were documented in the treatment-naïve group, a mortality rate of 2.39 per 100 person-years.

Three-quarters of the deaths were attributed to non-AIDS-related causes. The most common non-AIDS-related cause of death was cardiovascular disease (37%).

Compared to the ART-naïve group, immediate ART provided strong protection against mortality (aHR = 0.37, p < 0.001). Delayed ART also provided modest protection against mortality (aHR = 0.74, p = 0.04).

“In addition to the direct benefit of ART for survival, it is also likely that regular follow up and comprehensive care services associated with ART use contributed to the decreased mortality observed,” suggest the investigators. “After ART initiation, patients entered into the stable care system and received multidisciplinary services including regular medical visits as well as psychosocial support.”

Other factors associated with death were older age (under 50 years vs over 50 years, aHR = 2.03; p < 0.001), being male (aHR = 1.90; p < 0.001), having only a primary education or less (aHR = 1.85; p < 0.001), infection with HIV via heterosexual contact (aHR = 4.16, p < 0.001) or injecting drug use (aHR = 5.07; p < 0.001).

“Our results highlight the significant negative impact of delays in ART initiation in a real-world setting in China,” conclude the authors. “Our results support the urgent need to increase the number of PLWH identified early, and started on effective, long-term ART immediately, as predicted by the UN 90-90-90 targets.”