Although we are well into the third decade of the HIV epidemic, this study found that 23% of HIV-infected patients diagnosed with PCP at San Francisco General Hospital in the CART era came to medical attention late in the course of their HIV disease and were diagnosed concurrently with HIV and PCP. We found no significant change in the proportion of PCP cases with newly diagnosed HIV by study year. Patients with newly diagnosed HIV had more severely impaired oxygenation manifested by a higher alveolar-arterial oxygen gradient. Nevertheless, there were no differences in clinically important outcomes between the two groups except for an increased length of stay in patients newly diagnosed with HIV. To our knowledge, this is the largest single-center study of HIV-associated PCP in the CART era. No study since the early AIDS epidemic has specifically evaluated the severity and outcomes of PCP in patients with newly diagnosed HIV [9
One explanation for the similar outcomes between the two patient groups was that few patients with previously diagnosed HIV infection were taking PCP prophylaxis or CART, and therefore these individuals were no different physiologically or immunologically from those who were newly diagnosed with HIV. The median CD4 count was similar and not significantly increased even in the few patients who were taking CART. Because of the retrospective nature of our study, we were unable to verify whether patients who were classified as taking PCP prophylaxis or CART were adherent to their HIV regimens as prescribed.
We found that male gender and acquisition of HIV through high-risk sexual behavior were independently associated with newly diagnosed HIV. Prior studies of late HIV diagnosis, defined as diagnosis concurrent with an AIDS-defining condition or with a CD4 cell count less than 200 cells/μL, found that late diagnosis was less common in men who have sex with men compared to patients with other HIV risk factors (e.g. heterosexuals and IDU) [21
]. However, the majority of these studies were performed in European cohorts where the prevalence of injection drug use was low [21
]. One explanation for our findings may be that, compared to patients with high-risk sexual behavior, injection drug users in San Francisco have more interactions with the medical system before an overt AIDS-defining illness. Injection drug users have medical co-morbidities (e.g., skin and soft tissue infections, drug overdose or withdrawal) which require frequent contact with medical providers [24
], resulting in repeated opportunities for HIV testing. Another possibility, described in a study of homosexual men in San Francisco, is that patients with high-risk sexual behavior in San Francisco are more reluctant to undergo HIV testing [25
]. This may partly explain why male gender was associated with a new diagnosis of HIV infection, but there are clearly other confounding factors that we were unable to measure or account for. This study demonstrates a continued need for HIV education and earlier testing in all patients, but suggests that focusing on populations with high-risk sexual behavior may be particularly necessary and effective.
Although mortality was no different, physicians took longer to initiate PCP antimicrobial therapy in patients who were unaware of their HIV infection. Knowledge of underlying HIV infection clearly changes the physician’s pre-test suspicion of different diseases. At SFGH, initiating PCP therapy is usually done empirically while awaiting a definitive microscopic diagnosis. Physicians likely initiated antimicrobial treatment for other types of pneumonia (e.g., bacterial pneumonia) but delayed PCP treatment in patients who were not known to be HIV infected. In addition, oxygenation was more severely impaired in patients with a new HIV diagnosis. Patients who are unaware of their HIV infection may take longer to present for medical care, either from failure to recognize the severity of their illness or because they lack familiarity with the medical system. A study from the pre-CART era described similar findings, with PCP patients newly diagnosed with HIV having lower PaO2
compared to patients with known HIV [9
]. We did not find any other differences in admission vital signs or laboratory indices of organ dysfunction between the two groups. However, we did not collect data on duration or severity of symptoms or results of chest radiography, and are therefore limited in our ability to conclude that there were no other clinically significant differences in PCP presentation or severity between patients with newly and previously diagnosed HIV.
This study has several other limitations. The study was retrospective and limited to patients with a confirmed diagnosis of PCP at a university-affiliated public hospital. Patients at other institutions who are presumptively diagnosed with PCP may have different clinical manifestations or severity of disease compared to patients in our cohort. Furthermore, there was the potential to have misclassified patients into incorrect categories of newly versus previously diagnosed HIV. While this is a valid concern, we believe that both systematic and random miscategorization were unlikely. Our criteria for “newly” versus “previously” diagnosed HIV infection were stringent. Classification of HIV status was based on information from detailed histories. Patients classified as “newly” diagnosed with HIV infection had no past medical history related to underlying HIV infection and had no mention of definitive HIV infection in any admission note in the medical record. Subsequent progress notes documented a confirmatory HIV test after PCP diagnosis. For persons classified as “previously” diagnosed HIV infection, admission notes had to clearly document an earlier confirmatory HIV test either by patient self-report or by available medical records, typically with additional supportive information including CD4 count, history of opportunistic infections, and adherence to HIV treatment. Nevertheless, it is possible that a patient new to our medical system could have withheld information regarding an earlier diagnosis of HIV made at a different institution. This would bias our results toward the null hypothesis, but would not explain differences in oxygenation or HIV risk factors that we discovered between the two groups.
In conclusion, a significant number of patients at San Francisco General Hospital continue to be diagnosed with HIV only after presenting with PCP. The proportion of patients with concurrently diagnosed HIV and PCP each year remained unchanged during the study period. While oxygenation was more severely impaired in those with newly diagnosed HIV, there were no significant differences in mortality, ICU admission, or mechanical ventilation. Patients who acquired HIV via high-risk sexual activity were more likely to be newly diagnosed with HIV/AIDS than persons who acquired HIV via injection drug use. This study demonstrates a continued need for HIV education and earlier HIV testing, particularly in patients with high-risk sexual behavior.