Most HIV-positive patients do as well as HIV-negative counterparts following surgery

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In general, HIV-positive patients do no worse than HIV-negative patients after undergoing surgery, according to a retrospective study of 332 case-matched pairs by investigators from northern California. The study, published in the December issue of the Archives of Surgery found that most excess risk of infection (primarily bacterial pneumonia) or death following surgery was associated with a CD4 cell count below 50 cells/mm3 or a viral load over 30,000 copies/mL – which increased the risk of developing post-surgery-related complications fourfold and threefold, respectively.

Small studies examining the outcomes of HIV-positive patients undergoing surgery have reported conflicting results, both before and after the advent of potent antiretroviral therapy. Despite recent reports, for example regarding the success of heart surgery for HIV-positive individuals, the belief persists that HIV-positive individuals generally do worse after an operation compared with their HIV-negative counterparts, and some surgeons are still reluctant to perform surgery in otherwise healthy HIV-positive individuals.

332 case-matched pairs

In order to provide better answers regarding the issue of surgical outcomes in HIV-positive individuals, Dr Michael Horberg and colleagues at the Northern California site of the Kaiser Permanente Medical Care Programme studied 332 HIV-positive patients who underwent a wide variety of surgical procedures between 1997 and 2002.

They compared outcomes with 332 HIV-negative patients of the same age and gender, and who had undergone a similar procedure at around the same time and at the same location as one of the HIV-positive patients.

Glossary

pneumonia

Any lung infection that causes inflammation. The infecting organism may be bacteria (such as Streptococcus pneumoniae), a virus (such as influenza), a fungus (such as Pneumocystis pneumonia or PCP) or something else. The disease is sometimes characterised by where the infection was acquired: in the community, in hospital or in a nursing home.

matched

In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 

The HIV-positive patients – 68% of whom were receiving antiretroviral therapy prior to surgery – had been living with diagnosed HIV infection for a median of 8.4 years. Their median CD4 cell count at the time of surgery was 379 mm/3 and 61.5% had a plasma viral load below 500 copies/mL.

Surgical procedures studied included hernia repair (44% of all surgeries); appendix removal (17%); gallbladder removal (14%); hip or knee replacement (8%); coronary bypass or other heart surgery (6%); and six other major surgical procedures. There were no differences between the cases and the controls (mean age, 46.7 years; 91% male; 66% Caucasian), except that there were fewer people of Asian ethnicity and more of African American ethnicity amongst the HIV-positive patients.

Pneumonia seen more frequently in HIV-positive patients

The only complication that was seen more frequently among the HIV-positive patients was pneumonia (2.4% vs. 0.3%; p = 0.02). The eight incidences of bacterial pneumonia (and the one incidence of bacterial pneumonia in the HIV-negative patient) were resolved with antibiotics. However, one additional HIV-positive patient developed PCP and died 43 days after the surgical procedure.

More deaths after a year, but not likely related to surgery

The HIV-positive patients were five-times more likely to have died after a year compared with their HIV-negative counterparts (p=0.04), and the absolute risk difference for death at twelve months was 2.4%.

However, although the HIV-positive patients did have a higher mortality rate (10/332 vs 2/332; p = 0.02) none of the causes of deaths in the HIV-positive individuals were considered by the study’s authors to be related to their surgery, but rather other aspects of HIV disease primarily due to immunosuppression. “Of the ten HIV-infected patients who died within twelve months after the operation,” they note, “eight had CD4 cell counts less than 200 cells/mm3, with a median CD4 cell count of 101 cells/mm3.”

Increased risk: CD4 cell count 3, viral load > 30,000 copies/mL

A CD4 cell count below 50 cells/mm3 was associated with a statistically significant higher complication rate than a CD4 cell count above 50 cells/mm3 (36.4% vs. 10.0%; p = 0.006). After controlling for viral load, gender, anti-HIV therapy use, HIV risk factor, and ethnicity, this increased the risk of experiencing complications 4.34-fold (p = 0.09).

A viral load above 30,000 copies/mL was also associated with increased complications compared to a viral load below 30,000 copies/mL. After controlling for CD4 cell count, gender, HAART use, HIV risk factor, and ethnicity this increased the risk of experiencing complications 2.96-fold (p = 0.07).

However, a CD4 cell count below 200 cells/mm3 was not associated with higher complication rates compared with a CD4 cell count above 200 cells/mm3 (13.3% vs. 10.3%; p = 0.50), and the investigators also found that patients with a history of HAART use within 180 days of surgery had a similar complication rate as patients without a history of HAART use. (11.9% vs. 13.8%; p=0.69).

Strengths and limitations

There are several major strengths of this study that make its findings arguably robust, including its size, the wide varieties of common operations represented, and rigorous case-control matching.

However, there are several important limitations. The investigators do not appear to have included anyone infected, or co-infected, with hepatitis C, and they did not appear to include anyone with pre-existing lung, liver or kidney disease, nor report on a patients’ socioeconomic status – all of which could potentially affect outcome.

There may also have been some selection bias amongst the HIV-positive patients, since sicker patients may have been less likely to undergo surgery (the majority of operations were elective). It is also possible that there was over-reporting of the number of post-operative complications in the HIV-positive patients, since HIV-positive individuals may be admitted to hospital more readily than HIV-negative individuals with similar infections (e.g. bacterial pneumonia).

No other differences seen

The investigators note that although “concerns have been raised that HIV-infected patients have longer hospital stays and greater follow-up, affecting outcomes...we found nearly identical numbers of hospital days and surgical follow-up visits in HIV-infected and HIV-noninfected patients.”

In fact, no statistically significant differences were found for delayed wound healing, surgical site infections, wound rupture, number of complications, length of hospital stay, number of follow-up visits to the surgeon, or need for further operative procedures to treat surgical complications.

Conclusion

The investigators conclude by noting, “patients with HIV are living longer and regaining a substantial amount of immune function. Many HIV-infected patients will require surgical attention because of a variety of disorders. In many cases, HIV serostatus should not be a criterion when determining the need for surgery if patients have adequate viral control.”

References

Horberg MA et al. Surgical outcomes in human immunodeficiency virus–infected patients in the era of highly active antiretroviral therapy. Arch Surg 141: 1238-1245, 2006.