Studies have shown that AIDS-defining opportunistic infection (AIDS-OIs) were a leading cause of mortality and morbidity among patients with HIV prior to the advent of antiretroviral therapy (ART) in 1997. Despite substantial improvements in the treatment of HIV and OIs during the last 2 decades, data indicate that OIs remain a major contributor of HIV-related morbidity and mortality. Previous research has provided unclear results regarding the outcomes of HIV patients with OIs, and few were population-based. Recent estimates of survival following an AIDS-OI in the United States are lacking.


OI Survival Analysis

To examine whether survival following an OI has improved with advancements in HIV treatment, John T. Brooks, MD, and colleagues had a study published in the Journal of Infectious Diseases. The authors used HIV surveillance data to estimate survival probabilities after a first OI diagnosis among adults with AIDS in San Francisco during three treatment eras: 1981-1986, 1987-1996, and 1997-2012.

“Most patients meet the AIDS criteria from a national surveillance perspective based on their CD4 cell count,” explains Dr. Brooks, “but the San Francisco Department of Public Health has continuously monitored the clinical courses of all people infected with AIDS in the city, including survival after an OI.” The health department has collected data on initial and subsequent OIs—as well as CD4 cell counts, viral loads, immunizations received—and demographic information for nearly 21,000 patients through follow-ups approximately every 18 to 24 months.

“We found that survival has markedly increased following an AIDS-OI since 1981,” says Dr. Brooks (Figure). “The 5-year survival probability increased from 7% in 1981-1986 to 65% in 1997-2012.” The researchers suspect that this survival improvement likely reflects the use of combination ART, improved prophylaxis and treatment of AIDS-OIs, earlier diagnosis of HIV infection, and better linkage to effective HIV care.

“The advent of ART has probably had the largest effect on improved survival among patients with AIDS-OIs, along with improved treatment of OIs,” explains Dr. Brooks.  “In the 1980s, therapies weren’t available for many OIs, and we didn’t know how to treat most of the others. Now, we have effective therapies, and physicians are better at recognizing and treating OIs. Diagnostics have also improved for many OIs, and we have a better understanding of how to prevent OIs in those who are at risk by prescribing medication as prophylaxis.”


Room for Improvement

Although laudable progress has been achieved, Dr. Brooks says greater efforts are needed to address these infections. “A person with HIV today who is diagnosed before they’ve had profound loss of their CD4 cells and who receives effective therapy can expect to live a near normal lifespan,” he says. “The fact that many of our models estimated that patients with HIV can expect to live a virtually normal lifespan is reassuring. However, more than one-third of patients with an AIDS-OI die within 5 years. We didn’t expect to find this considering that excellent treatments are now available for most OIs. Based on our experience and anecdotal evidence, we hypothesize that survival was lower than expected because many patients don’t receive an HIV diagnosis until they have advanced disease.”

When analyzing individual AIDS-OIs, the researchers found that survival improved remarkably throughout the study period for patients with the top four most common OIs: Pneumocystis pneumonia (PCP), Kaposi sarcoma, esophageal candidiasis, and disseminate Mycobacterium avium complex. The largest survival improvement was seen for HIV-infected patients with PCP; this is likely explained by the 1989 recommendation for PCP prophylaxis for HIV-infected patients with a CD4 cell count below 200 cells/mm3. However, survival remained low for multiple OIs, including brain lymphoma and progressive multifocal leukoencephalopathy.


Putting Findings to Use

According to Dr. Brooks, the study findings stress the importance of diagnosing and recognizing AIDS-OIs among at-risk patients and understanding how to manage these infections. “Clinicians should also consult their colleagues early when an OI is suspected, if need be,” he says. “Infectious disease (ID) specialists should also help their frontline provider colleagues keep HIV at the top of mind and test everyone for HIV in order to identify the infection as early as possible. Doing so can give patients the greatest chance of getting into effective care and ensure that they maximize benefits from using ART. It may also help patients avoid developing an AIDS-OI. In addition, ID specialists can further assist patients by working with their institutions to make HIV testing a routine part of good general healthcare.”