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People with HIV Still at Risk for Opportunistic Illness Death Despite Dramatic Survival Gains

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The risk of death due to opportunistic illnesses (OIs) has declined dramatically since the advent of combination antiretroviral therapy (ART) in the mid-90s, but even in the era of effective ART about a third of people diagnosed with a first OI died within 5 years, according to an analysis of more than 20,000 people living with HIV in San Francisco.

Untreated HIV infection typically leads to severe immune dysfunction within a matter of years, leaving people prone to opportunistic infections and cancers that can usually be kept under control by a healthy immune system.

It is well known that that the development of effective combination treatment led to a steep drop in the occurrence of OIs and a decline in overall mortality among people with HIV/AIDS. A previous study showed that the incidence of AIDS-defining OIs in San Francisco fell by as much as 99% from 1993 to 2008. However, the effect of specific OIs on death rates has not been fully described.

As reported in the June 3 advance edition of Journal of Infectious Diseases, Kpandja Djawe from the Centers for Disease Control and Prevention and colleagues examined whether improved HIV treatment was associated with better survival after diagnosis of AIDS-defining opportunistic illnesses, and how survival differed by OIs.

The researchers looked at surveillance data collected by the San Francisco Department of Public Health from 20,858 adult people with AIDS in the city starting in 1981. A majority were gay white men with a median age of about 40 years, but over time the demographics shifted toward more black and Hispanic/Latino men and women who acquired HIV through injection drug use or heterosexual transmission. 

They estimated survival probabilities after a first AIDS-defining OI diagnosis during 3 treatment eras: 1981-1986 (no effective treatment), 1987-1996 (NRTI monotherapy or dual therapy only), and 1997-2012 (effective multi-class combination ART). The data included 3002 people diagnosed during the first period, 14,097 diagnosed during the second period, and 3759 diagnosed during the third period.

Results

  • A total of 17,099 patients died over the course of the observation period, including 2957 during the first period (98%), 12,569 during the second period (89%), and 1573 during the third period (42%).
  • After adjusting for confounding factors, the overall 5-year survival probability among people diagnosed with AIDS OIs increased from 7% during 1981-1986 to 18% during 1987-1996 to 65% during 1997-2012.
  • Stated another way, adjusted 5-year mortality rates decrease from 93% to 82% to 35%, respectively.
  • The largest survival gain was seen for Pneumocystispneumonia, rising from just 1% during the first period to 69% during the third period.
  • The most common AIDS-defining OIs were Pneumocystis pneumonia (8163 cases), Kaposi sarcoma (4195 cases), HIV wasting syndrome (1864 cases), esophageal candidiasis (1381 cases), Mycobacterium avium complex (1069 cases), HIV-related encephalopathy (932 cases), extrapulmonary cryptococcosis (883 cases), cryptosporidiosis (694 cases), immunoblastic lymphoma (676 cases), and cytomegalovirus disease excluding retinitis (643 cases).
  • The 5 least frequently diagnosed AIDS-defining OIswere isosporiasis (36 cases), disseminated coccidioidomycosis (32 cases), recurrent Salmonella septicemia (19 cases), and invasive cervical cancer (12 cases).
  • During 1997-2012, adjusted mortality rates were highest for brain lymphoma and progressive multifocal leukoencephalopathy.

A limitation of this analysis is that the combination ART era is quite long and has seen substantial changes in treatment. Early combination regimens were harder to take, had worse side effects, and did not control HIV replication as well as modern regimens, especially for people with drug-resistant virus. Breaking down this time period might show that current OI death rates are lower than those in the mid-1990s and early 2000s.

"Survival after first AIDS-OI diagnosis has improved markedly since 1981," the study authors concluded. "Some AIDS-OIs remain associated with substantially higher mortality risk than others, even after adjustment for known confounders. Better prevention and treatment strategies are still needed for AIDS-OIs occurring in the current HIV treatment era."

"While recent research suggests that many opportunistic infections in the U.S. are now less common and, oftentimes, less lethal, we cannot forget about them, Djawe said in a press release issued by the Infectious Diseases Society of America. "We need to keep them in mind, even in the context of the changing epidemiology of HIV."

"Better prevention and treatment strategies, including earlier HIV diagnosis, are needed to lessen the burden of AIDS opportunistic infections, even today, in the combination ART era," added co-author Sandra Schwarcz, an HIV epidemiologist at the San Francisco Department of Public Health.

Today in the U.S. serious immune deficiency and resulting OIs are mainly seen among people who are not diagnosed with HIV until late in the course of infection. People who start treatment but do not achieve sustained viral suppression and good CD4 T-cell recovery also remain at risk.

San Francisco is known for its good health care for people with HIV, and areas with less access to expert care may have higher OI death rates. Nationwide, the CDC estimates that 86% of people living with HIV in 2011 had been diagnosed, 37% were prescribed ART, and only 30% achieved an undetectable viral load.

"The importance of the so-called cascade of care, comprising early HIV diagnosis, effective linkage to care, long-term retention in care, and durable viral suppression, has long been recognized as being critical to attaining control over various aspects of the epidemic, including achieving good clinical outcomes in infected individuals," Henry Masur and Sarah Read from the National Institute of Allergy and Infectious Diseases wrote in an accompanying commentary.

"San Francisco may be a best-case scenario for reducing mortality risk associated with AIDS-related opportunistic infections," they continued. "However, even with >30 years of effort and engagement of all relevant stakeholders in San Francisco, the current report illustrates that HIV-related opportunistic infections continue to occur and that patients still die at alarming rates during the early years after their first AIDS-related opportunistic infection is recognized...A 35% mortality rate within 5 years of diagnosis of the initial AIDS-defining opportunistic infection leaves considerable room for improvement."

7/9/15

References

K Djawe, K Buchacz, L Hsu, et al. Mortality Risk After AIDS-Defining Opportunistic Illness Among HIV-Infected Persons -- San Francisco, 1981-2012. Journal of Infectious Diseases. June 3, 2015 (Epub ahead of print).

H Masur and S Read. Opportunistic Infections and Mortality: Still Room for Improvement. Journal of Infectious Diseases. June 3, 2015 (Epub ahead of print).

Other Source

Infectious Diseases Society of America. Thirty Years of AIDS Data Highlight Survival Gains, Room for Improvement. Press release. June 4, 2015.