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Large study confirms near-normal life expectancy for many people on HIV treatment

Prior to the availability of effective HIV treatment (ART) people with HIV had a relatively shortened lifespan, with most expected to live for around 10 years after infection. However, beginning in 1996, effective HIV treatment became available in Canada and other high-income countries. By suppressing HIV to very low levels, ART significantly reduces the ability of this virus to damage the immune system. Also, ART greatly reduces HIV-related excess inflammation and activation of the immune system. All of these effects allow the immune system to make repairs and largely rebuild itself. As a result, in the vast majority of ART users, the immune system becomes stronger with higher CD4+ cell counts and the risk of dying from AIDS-related complications greatly diminishes.

In the first decade that ART was available, there were some downsides, such as the following:

  • ART had many side effects
  • there were food and water restrictions for some medications
  • regimens required taking a large number of pills – two or even three times daily

As a result, some people interrupted ART and others may have had poor adherence. Such interruptions to therapy allowed the virus to re-surge and inflammation to increase, which could have degraded survival.

Since that era, treatments have become simplified and they are much safer and more powerful. Many people who initiate ART in the current era are prescribed an entire regimen in a pill, just once daily. Leading drugs that anchor such regimens include the following:

  • bictegravir – in Biktarvy
  • dolutegravir – sold as Tivicay and co-formulated with other drugs and sold in pills called Dovato, Juluca, and Triumeq
  • doravirine – sold as Pifeltro and co-formulated with other drugs in a pill called Delstrigo

In the past several years, a regimen of two HIV drugs became available (sold as Cabenuva) that can be injected once a month or every two months, greatly simplifying adherence requirements.

Another change from the early ART era is that around 2015, based on data from clinical trials, treatment guidelines greatly encouraged the initiation of ART as soon as a diagnosis of HIV was made.

Due to these improvements in HIV treatment—better treatments and earlier initiation of ART—it is important to review changes in life expectancy in people with HIV in the current era.

A team of researchers in Europe and North America, including southern Alberta, merged information from 20 databases and reviewed and compared changes in life expectancy in 206,891 people who initiated ART between 1996 and 2014 or between 2015 and 2019.

The researchers found that between 1996 and 2019 about 3% of people died. They also found that among people with high CD4+ cell counts who started ART prior to 2015 and who survived to 2015 or who started ART after 2015, “life expectancy was only a few years lower than in [people without HIV].” However, among people who had low CD4+ cell counts when they initiated ART (regardless of the time period), prospects for survival were generally poorer.

In general, men had reduced life expectancy compared to women. People who injected drugs had reduced life expectancy compared to people who did not inject drugs.

Overall, the present study confirms earlier research that found that ART has long-term benefits, greatly narrowing the survival gap between people with and without HIV. The study was a snapshot of some immunological and virological data and linked the data to records about survival from medical databases.

To ensure that more people with HIV reach the life expectancy of HIV-negative people, the researchers emphasize the importance of “early [HIV] diagnosis and sustained treatment of HIV.” However, more attention needs to be paid to the broader needs of people with HIV, including reducing the risk for and managing comorbidities (such as heart, liver, lung and kidney disease, cancer prevention and treatment) as well as support for mental health. In addition, access to harm reduction services for people who inject drugs and support for reducing alcohol consumption and smoking are also needed.

Results

In general, people who initiated ART in the earlier part of the study, particularly the years 1996 to 1999, had a greater risk of death. Beginning in 2015, when recommendations to start ART were extended to all people with HIV (regardless of CD4+ cell count or duration of infection), researchers found that the risk of death fell compared to the early ART era (1996 to 1999).

People who initiated ART prior to 2015 had a higher risk of death. The factors that were linked to an increased risk of death included having less than 500 CD4+ cells/mm3, having a high viral load, a diagnosis of an AIDS-related infection or cancer, and chronic hepatitis C virus (HCV) infection.

Life expectancy

To estimate life expectancy, researchers divided people into two groups:

  • those who initiated ART before 2015
  • those who initiated ART in 2015 or later

They then divided people based on their CD4+ cell count at the time they entered the study and their sex assigned at birth.

Overall, people who initiated ART prior to 2015 had reduced life expectancy compared to people who initiated ART in 2015 or later. The CD4+ counts were also important. In general, people who began ART with low CD4+ counts had reduced life expectancy compared to people who began ART with higher CD4+ counts.

In people without HIV, women tend to have a longer life expectancy than men. This was also the case among women with HIV in this study.

The researchers found that people who acquired HIV as a result of sharing equipment for drug use had shorter life expectancy than people who acquired it in other ways. Also, people who had AIDS when they entered the study had shorter life expectancy than people who did not have AIDS.

Life expectancy among women

ART – overall impact on survival

Among women who began ART before 2015 and who were 40 years of age, researchers estimated that they would live for 36 more years—for a total of 76 years.

Among women who began ART in 2015 or later at 40 years old, life expectancy would be about 39 more years—for a total of 79 years.

Note that the above figures are overall estimates. Researchers found that CD4+ cell counts at the time that ART was initiated could have a huge impact on life expectancy, as shown by the following:

Starting ART at low or high CD4+ cell counts prior to 2015

Among women who started ART before 2015 and who had low CD4+ cell counts (less than 50 cells/mm3), their remaining life expectancy at age 40 would be 19.4 years, for a total survival of 59.4 years. Women who initiated ART at higher CD4+ cell counts could expect longer life expectancy, reaching as high as 40.2 additional years if they began treatment at age 40 (for a total of 80.2 years of life expectancy). This higher figure was found in women who initiated ART when their CD4+ counts were 500 cells/mm3 or greater.

Starting ART at low or high CD4+ cell counts after 2015

Among women who initiated ART at age 40 after 2015 with less than 50 CD4+ cells/mm3, life expectancy was 25 additional years, for a total of 65 years. However, among women who initiated ART with a CD4+ count of 500 or more cells/mm3 at age 40, life expectancy was projected to reach an additional 40 years, for a total of 80 years.

Among women without HIV, life expectancy at age 40 after 2015 was estimated to be an additional 45.8 years, for a total of nearly 86 years.

Life expectancy among men

ART – overall impact on survival

Among men who began ART before 2015 and who were aged 40, researchers estimated that they would live for 34.5 more years—for a total of 74.5 years.

Among men who began ART in 2015 or later and who were aged 40, researchers estimated that they would live for 37 more years—for a total of 77 years.

However, results could be different depending on the CD4+ count when ART was initiated, with people who started ART at higher CD4+ counts having a longer life expectancy.

Starting ART at low or high CD4+ cell counts prior to 2015

Among men who began ART prior to 2015 and who had very low CD4+ counts (less than 50 cells/mm3), their remaining life expectancy at age 40 would be 18.2 years, for a total of 58.2 years. Life expectancy increased when ART was initiated at higher CD4+ cell counts in this period. For instance, among men who started ART when they had 500 or more CD4+ cells, life expectancy at age 40 would be an additional 38 years, for a total of 78 years.

Starting ART at low or high CD4+ cell counts in 2015 or later

Among men who were aged 40 and who started ART in 2015 or later with less than 50 CD4+ cells/mm3, researchers estimated that they had an additional 23.7 years of life expectancy, for a total of 63.7 years. However, among men who initiated treatment in this period with a CD4+ cell count of 500 or more cells/mm3, life expectancy at age 40 was projected to reach an additional 39.2 years, for a total of 79.2 years.

Among HIV-negative men, life expectancy at age 40 after 2015 was estimated to be an additional 40.7 years, for a total of 80.7 years.

Life expectancy – considering age and gender

Women

The researchers estimated that overall life expectancy at age 20 among women who began ART prior to 2015 was 72 years. Among women who began ART at age 20 in 2015 or later, life expectancy was estimated to be 77 years.

Men

The researchers estimated that overall life expectancy at age 20 among men who began ART prior to 2015 was 71 years. Among men who began ART at age 20 in 2015 or later, life expectancy was projected to be 75 years.

Bear in mind

The study’s findings are estimates and some people may live for longer or shorter periods depending on personal circumstances. As studies continue to monitor life expectancy over longer periods, estimates of life expectancy will become more precise.

Part of the reason that people were more likely to die in the early ART era (1996 to 1999) was that they were exposed to more toxic drugs (which made adherence difficult) and were likely sicker than people in the latter period of the study. Despite this, the researchers stressed that two factors—age and CD4+ count around the time they began ART—were “the factors most strongly associated with [the risk of death] from 2015 onward.”

Thus, a young adult who is infected today and who is diagnosed and initiates ART shortly thereafter should live well into their senior years, all other things being equal.

Inequalities

Not every ART user will have such a rosy future. In people without HIV, life expectancy can be affected by socio-economic issues, which were not measured in the study. Also, people in this study who injected drugs had significantly reduced survival compared to people who did not inject drugs.

Other studies of people with HIV in the U.S. have found that people who inject drugs have reduced survival compared to people who don’t inject drugs. The same study also found that Black men have reduced survival compared to White men. The present study did not analyse data by race/ethnicity.

Life expectancy and beyond

The present study underscores efforts to improve life expectancy among people with HIV. The researchers call for continued efforts on early diagnosis of HIV and sustained treatment. This means that more opportunities need to be made for HIV testing and swift referral to care. There also needs to be a focus on supporting the mental health needs of people with HIV, as mental health issues can affect adherence to ART. Some people who use drugs, alcohol and tobacco also need harm reduction services. However, there are other issues that can also affect health, such as coinfection with hepatitis B and C viruses and monitoring for cancer.

In addition to life expectancy, efforts (and funding) are needed to help clinics focus on improving quality of life for people with HIV. This can include more widespread use of modern, tolerable and effective therapy. However, studies are needed to understand the issues that affect quality of life and to craft interventions to maintain or improve it.

—Sean R. Hosein

REFERENCES:

  1. Trickey A, Sabin CA, Burkholder G, et al. Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies. Lancet HIV. 2023 May;10(5):e295-e307. 
  2. Klein MB. Living longer with HIV: gains for some but not for all. Lancet HIV. 2023 May;10(5):e275-e276.
  3. Uusküla A, Feelemyer J, Des Jarlais DC. HIV treatment, antiretroviral adherence and AIDS mortality in people who inject drugs: a scoping review. European Journal of Public Health. 2023 Jun 1;33(3):381-388.