Issues unrelated to HIV are affecting survival

Since 1996, the availability of potent combination anti-HIV therapy (ART) in Canada and many high-income countries has led to significantly reduced rates of AIDS-related illness and death, at least among people who are aware of their infection and who take ART every day exactly as directed so that the amount of HIV in their blood is suppressed. As a result of sustained use of ART, many HIV-positive people will live into their senior years. Furthermore, clinical trials have shown that HIV-positive people who initiate ART and achieve and maintain an undetectable viral load do not pass on HIV to their sexual partners. However, researchers are increasingly finding that some, perhaps many, HIV-positive people have co-existing health conditions—these are called co-morbidities.

A large observational database called ART-CC (Antiretroviral Therapy Cohort Collaboration) has amassed health-related information from leading clinics in Western Europe and North America. In Canada, clinics in southern Alberta and British Columbia participate in ART-CC. From time to time the researchers involved in ART-CC analyse their data and issue reports.

A recent analysis from ART-CC focused on data from nearly 125,000 HIV-positive people who initiated ART between 1996 and 2014 and were subsequently monitored. The ART-CC researchers sought trends in illnesses both related and unrelated to HIV.

The researchers found that deaths from complications unrelated to AIDS were twice as high as deaths due to AIDS-related complications. Interventions, some of which are discussed later in this report, are needed to prevent deaths from all causes in HIV-positive people.

Study details

The ART-CC enrolled adults who entered the study upon initiating ART. The present analysis focused on 124,537 participants whose average profile at the start of the study was as follows:

• 76% men, 24% women
• age – 38 years
• CD4+ count – 244 cells/mm³
• viral load – 67,000 copies/mL
• the researchers grouped participants based on how they were infected, as follows: heterosexual sex – 35%; gay/bisexual men having sex with other men – 35%; injecting street drugs – 17%; receiving contaminated blood transfusions – 1%; and in the remainder of cases, no information was available as to how HIV infection occurred
• length of time in the study – five years

Results

About 11% of participants developed an AIDS-related illness. Such illness can occur in the first several months after initiating ART, depending on the degree of weakness of the immune system. ART helps the immune system to begin repairing itself, but these repairs take time.

The researchers focused on three AIDS-related complications because they were interested in finding out more about them. The proportions of participants who developed these complications are as follows:

• TB (tuberculosis) – 15%
• PCP (Pneumocystis pneumonia) – 13%
• NHL (non-Hodgkin’s lymphoma) – 7%

Note that half of the participants had fewer than 245 CD4+ cells when they entered the study. In light of this, it should not be surprising that these complications occurred.

Deaths

There were 11,280 deaths during the study, which were distributed as follows:

• AIDS related – 24%
• unrelated to AIDS – 36%
• unknown – 40%

Here is the distribution of deaths from causes unrelated to AIDS:

• cancers – 24%
• “accident/suicide/overdose” – 17%
• cardiovascular disease – 16%
• serious infections unrelated to AIDS – 15%
• liver complications – 13%
• lung complications – 3%

Preventing AIDS-related complications

AIDS-related complications occur because of a weakened immune system. Generally, such complications become an issue when the CD4+ count has fallen below 200 cells/mm³ or lower. To reduce the risk of people becoming susceptible to AIDS-related infections, the ART-CC researchers recommended that people at risk for HIV be offered the following:

• frequent HIV testing (so that the infection can be diagnosed in the early stages)
• early initiation of ART

Preventing complications unrelated to HIV

As issues unrelated to AIDS caused many deaths in the study, the researchers called for reducing the factors that increase the risk of death unrelated to AIDS.  To do this, screening for at least the following issues would be needed:

• co-infection with hepatitis B and C virus infections
• smoking
• kidney injury
• human papillomavirus–related growths in the ano-genital area and mouth/throat
• cardiovascular disease
• anxiety, depression and other mental health conditions
• excess weight
• problematic substance use
• adherence to HIV treatment

Should screening find these issues, potential interventions could include the following:

• treatment for hepatitis B or hepatitis C virus
• a vaccine is also available for hepatitis B virus for people at risk of this infection
• smoking cessation
• treatment of cardiovascular disease, including advice (via referral to a registered dietitian if available) about healthy eating, an exercise program and the use of medication to help normalize blood pressure and lipid levels in the blood
• referral to alcohol or harm reduction and drug treatment programs

The ART-CC does not collect information about substance use, mental health and body mass index (BMI). Also, 40% of the causes of death were missing from the present analysis, as this data had not been supplied by the clinics that participate in the ART-CC. However, researchers performed a sensitivity analysis, removing clinics that did not send sufficient data, and found that the overall trends discerned in the larger analysis were still present. This suggests that health problems unrelated to AIDS will become even more of an issue for HIV-positive people over time. If the full benefits of ART—near-normal life expectancy—are to be experienced by more people, attention must be paid to factors that appear to be increasingly affecting HIV-positive people and their survival. By screening for and treating these conditions, quality of life can also be maintained or even improved.

—Sean R. Hosein

REFERENCE:

Pettit AC, Giganti MJ, Ingle SM, et al. Increased non-AIDS mortality among persons with AIDS-defining events after antiretroviral therapy initiation. Journal of the International AIDS Society. 2018 Jan;21(1).