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Deaths Due to Late HIV Diagnosis Still a Problem

July 11, 2013

In high-income countries such as Canada, Australia and the U.S. and in regions such as Western Europe, the widespread availability of potent combination anti-HIV therapy (commonly called ART or HAART) has significantly reduced deaths from AIDS-related infections. The benefit of ART is so profound that researchers predict that a young adult today who begins treatment shortly after diagnosis, who has minimal co-existing health conditions and who takes treatment every day exactly as directed should have a near-normal life expectancy.

However, this rosy forecast is dependent on HIV testing at a very early stage of HIV disease. About 25% of Canadians who have HIV are not aware of their infection status and several other high-income countries also have significant proportions of undiagnosed HIV infections. Expansion of HIV testing opportunities -- wherein an HIV test is offered and followed up with counselling and swift referral to clinics -- needs to be made more available in Canada and elsewhere. If not, it is likely that some people who are not aware of their infection status will become very ill before they are diagnosed and can receive ART. Waiting to seek care until the immune system is severely weakened increases the chances of developing serious, life-threatening complications. Furthermore, treating someone with a life-threatening infection and its accompanying complications is very expensive for emergency rooms and infectious disease departments of hospitals.

Researchers at Public Health England have been analysing trends in deaths among HIV-positive people over the decade 1999 to 2008. During that time, deaths among HIV-positive people generally declined. However, even in recent years, the risk of death among HIV-positive people was still elevated compared to that among HIV-negative people of the same age or gender. The researchers stated: "Earlier diagnosis [of HIV] could have prevented 1,600 AIDS-related deaths over the decade." They also added that their findings "highlight the need to intensify efforts to offer and recommend an HIV test in a wider range of clinical and community settings."


Study Details

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Health-related information collected from adults diagnosed with HIV in England and Wales was analysed along with reports of deaths registered with the Office of National Statistics.

Researchers also constructed a case-control study by comparing data from each person with HIV who died (cases) to that of four other people with HIV who did not die (controls) during the study period.


Results

The proportion of HIV-positive people aged 15 to 59 years tripled from 17,375 people in 1999 to 53,802 people in 2008.

The number of deaths among HIV-positive people grew "marginally," from 408 in 1999 to 519 in 2008.

The proportion of HIV-positive people who died decreased about threefold over the course of the study, from 217 per 10,000 people to 82 per 10,000 people.

In general, proportionally more men died than women.


Comparisons With HIV-Negative People

Despite the relative widespread availability of ART in England and Wales, in 2008 the researchers found that the overall rate of death among HIV-positive people "remained more than five times higher" than it did among HIV-negative people. The specific death rates in that year were as follows:

  • HIV positive -- 82 deaths per 10,000 people
  • HIV negative -- 15 deaths per 10,000 people


Different Age Groups

When they examined the rate of death for people aged 15 to 59 years, researchers found that among HIV-positive people it was "almost 13 times higher" than it was among HIV-negative people.

The rate of death in HIV-positive people aged 30 to 49 years was six times greater than it was in HIV-negative people.


Gender and Age

In women aged 15 to 29 years, the rate of death was 21 times greater among HIV-positive people than it was among HIV-negative people.

Overall, the rate of death for HIV-positive men was five times greater than it was among HIV-negative men.

For men in the same age group, the rate of death was nine times greater among HIV-positive people than it was among HIV-negative people.

The death rate for people who injected street drugs was about 20 times greater if they were HIV positive compared to HIV-negative people who did not inject street drugs. However, the researchers found that the rate of death in HIV-positive people who injected street drugs was "not too dissimilar" from that in HIV-negative people who also injected street drugs.


Causes of Death

According to the researchers, a major contributing factor to the deaths of HIV-positive people in this study was the late diagnosis of HIV disease. They found that among nearly 80% of adults who died, HIV was diagnosed when their CD4+ count was less than 350 cells. When the CD4+ count falls below this level, serious immune deficiency has developed.

About 50% of HIV-positive people in the study who died did so within four months of being diagnosed with HIV. Furthermore, 64% of HIV-positive people who died did so within a year of their diagnosis.

Causes of death were mostly due to AIDS-related infections and cancers. Here are some that occurred in the study:

  • AIDS-related pneumonia (PCP, also known as PJP, and bacterial pneumonia)
  • non-Hodgkin's lymphoma
  • TB (tuberculosis)
  • KS (Kaposi's sarcoma)
  • PML (progressive multifocal leukocencephalopathy)
  • Toxo (toxoplasmosis)
  • Crypto (cryptosporidiosis)

The proportion of AIDS-related deaths was greater among people who identified as heterosexual and who were infected via sex, regardless of whether they were infected in the UK or overseas.


Cases vs. Controls

In analysing data, when comparing HIV-positive people who died from AIDS-related causes to HIV-positive people who remained alive, researchers made the following findings:

  • being diagnosed late with HIV was linked to an 11-fold increased risk of death
  • injecting street drugs was linked to a nearly threefold increased risk of death

In contrast, people who were taking ART as well as those who were aged 50 years or older were significantly less likely to die.

Late diagnosis of HIV -- and therefore delayed initiation of ART -- had a profound impact on survival. Researchers estimated that 81% of all AIDS-related deaths and 61% of all non-AIDS-related deaths were likely caused by late HIV diagnosis.


Predictions Not True for All

The prediction that many HIV-positive people in high-income countries such as Canada can have a near-normal lifespan is based on at least the following assumptions:

  • HIV-positive people are diagnosed at an early stage of the disease
  • people initiate ART shortly after an early HIV diagnosis

However, based on the data from England and Wales, it seems that in a sizeable fraction of HIV-positive people these assumptions may not hold true. In their study, the researchers noted that late HIV diagnoses continue to occur in the following key populations:

  • men who have sex with men (MSM)
  • people who have emigrated from countries and regions where HIV is relatively common, such as parts of sub-Saharan Africa

The researchers call for expanded testing opportunities and the prioritization of HIV testing "in a range of health care and community settings." Hopefully, such testing will be accompanied by counselling, safeguards for confidentiality and swift referrals to care and treatment.


References

  1. Simmons R, Ciancio B, Kall M, et al. Ten-year mortality trends among persons diagnosed with HIV infection in England and Wales in the era of antiretroviral therapy: AIDS remains a silent killer. HIV Medicine. 2013; in press.
  2. Gustafson R, Montaner J, Sibbald B, et al. Seek and treat to optimize HIV and AIDS prevention. Canadian Medical Association Journal. 2012 Dec 11;184(18):1971.
  3. Sabin C. Review of life expectancy in people with HIV in settings with optimal ART access: what we know and what we don't. In: Program and abstracts of the 11th International Congress on Drug Therapy in HIV Infection, 11-15 November 2012, Glasgow, UK. Abstract O131.
  4. May M, Gomples M, Sabin C, et al. Impact on life expectancy of late diagnosis and treatment of HIV-1 infected individuals: UK Collaborative HIV Cohort Study. In: Program and abstracts of the 11th International Congress on Drug Therapy in HIV Infection, 11-15 November 2012, Glasgow, UK. Abstract O133.
  5. Lohse N, Hansen AB, Pedersen G, et al. Survival of persons with and without HIV infection in Denmark, 1995-2005. Annals of Internal Medicine. 2007 Jan 16;146(2):87-95.
  6. Lohse N, Hansen AB, Gerstoft J, et al. Improved survival in HIV-infected persons: consequences and perspectives. Journal of Antimicrobial Chemotherapy. 2007 Sep;60(3):461-3.
  7. Søgaard OS, Lohse N, Østergaard L, et al. Morbidity and risk of subsequent diagnosis of HIV: a population-based case control study identifying indicator diseases for HIV infection. PLoS One. 2012;7(3):e32538.
  8. Krentz HB, Gill MJ. Cost of medical care for HIV-infected patients within a regional population from 1997 to 2006. HIV Medicine. 2008 Oct;9(9):721-30.



This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication CATIE News. Visit CATIE's Web site to find out more about their activities, publications and services.
 

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