HIV/AIDS
MAJOR ARTICLE
Rates of Postoperative Complications among Human Immunodeficiency Virus– Infected Women Who Have Undergone Obstetric and Gynecologic Surgical Procedures Thomas A. Grubert,1 Daniela Reindell,1 Ralph Ka¨stner,1 Bernd H. Belohradsky,2 Lutz Gu¨rtler,3,a Manfred Stauber,1 and Olaf Dathe1 Departments of 1Gynecology and Obstetrics and 2Pediatrics, and 3Pettenkofer Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University of Munich, Germany
Clinical observations indicate that human immunodeficiency virus (HIV)–positive women experience more postoperative problems than do HIV-negative women. To obtain a better estimate of the individual risk of postoperative morbidity among HIV-infected women, and to determine which procedures pose the greatest risk, we performed a retrospective case-control study in which we assessed the outcomes after 235 obstetric and gynecologic surgical procedures. For purposes of comparison, an HIV-negative control patient was matched for each of the 235 surgical procedures performed, on the basis of the type of procedure and patient age. We found a significantly greater number of postoperative complications among the HIV-positive women. Higher complication rates occurred after abdominal surgery (odds ratio [OR], 3.6; P p .001 ) and curettage (OR, 7.7; P p .06). Among HIV-infected women, the risk of complications was associated with immune status. Antiretroviral therapy and standard perioperative antibiotic prophylaxis did not decrease the risk of complications. Indications for performing abdominal surgery and curettage on HIV-infected women should be carefully weighed against the potential risk of postoperative complications. In the Northern Hemisphere, the proportion of women among HIV-infected individuals has been steadily increasing during the past 10 years, and, worldwide, it is estimated that 47% of HIV-infected individuals are women [1]. In the United States and Europe, estimates of the proportion of women among HIV-infected individuals range from 20% to 30% [1, 2]. Meanwhile, significant progress has been achieved in the treatment
Received 8 June 2001; revised 18 October 2001; electronically published 11 February 2002. a Present affiliation: Loeffler Institute of Medical Microbiology, University of Greifswald, Greifswald, Germany.
Reprints or correspondence: Dr. Thomas A. Grubert, I. Frauenklinik der LudwigMaximilians-Universita¨t, Maistrasse 11, D-80337 Mu¨nchen, Germany (Thomas
[email protected]). Clinical Infectious Diseases 2002; 34:822–30 2002 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2002/3406-0013$03.00
822 • CID 2002:34 (15 March) • HIV/AIDS
of HIV-infected patients. Combination antiretroviral therapy (ART) has significantly improved patient survival rates, even among patients with advanced-stage HIV disease [3–5]. Because of improved patient survival rates, the number of operations performed on HIV-infected women will probably increase in the future. Among HIV-infected women, cervical neoplasia is highly prevalent. As the life expectancy of these patients increases, so, too, will their chance of undergoing gynecologic surgery at some point for treatment of this condition. Furthermore, the improved outlook for survival often leads HIV-infected women to have a more positive attitude toward reproduction, which, in turn, leads to increased pregnancy rates for this group. Because recent reports have shown that delivery of infants by cesarean section independently reduces the rate of vertical transmission of HIV [6, 7], we will also see an increase in the number
of pregnant HIV-infected women who undergo cesarean section. HIV-infected individuals have a higher risk of developing infectious complications after surgery [8, 9], even after minor procedures [10]. Published data on this topic mainly have focused on HIV-infected males. Only a few studies of HIV-infected females and, in particular, HIV-infected females undergoing obstetric or gynecologic surgery have been published. These studies have also suggested a markedly elevated risk of postoperative morbidity in this group [11–14]. To obtain further information about the risks faced by HIVinfected women who undergo obstetric and gynecologic surgical procedures, we conducted a case-control study of 235 surgical procedures performed on 173 HIV-positive women. Our objective was to determine which procedures pose the greatest risk for postoperative complications and to identify specific postoperative problems. This information would then enable us to better estimate individual risk and develop strategies to minimize postoperative morbidity in these patients in the future.
PATIENTS AND METHODS We have been treating HIV-infected women at our specialized outpatient clinic (I. Department of Gynecology and Obstetrics, Ludwig-Maximilians University of Munich) since 1989. As of June 1999, we had performed 235 obstetric and gynecologic surgical procedures on 173 women. To compare the clinical outcomes of HIV-infected patients with those of control patients, we matched an HIV-negative patient to each surgical procedure performed on an HIV-positive patient by selecting from our surgical records the first eligible case after the index case. Patient age and the type of surgical procedure performed were used as criteria for matching. For our evaluation, the 235 surgical procedures were classified into 6 categories: abdominal surgery (n p 72; e.g., abdominal hysterectomy, ovariectomy, tubectomy, and cesarean section); endoscopic procedures (n p 10 ); minor procedures with an intrauterine component (n p 72 ; e.g., abortion and curettage); cervical surgery (n p 55 ; e.g., cervical biopsy, Loop electrosurgical excision of the transformation zone, cold-knife cone biopsy, laser vaporization, and cerclage); vulvar surgery (marsupialization [n p 1 ] and episiotomy [n p 22]); and breast surgery (n p 3). A detailed analysis of the subset of cesarean sections included in the “abdominal surgery” category has been published elsewhere [13]. Diagnosis of HIV infection in the study group patients was done by means of anti–HIV-1 ELISA and was confirmed by Western blot analysis. Since 1995, measurement of virus loads has been performed on a regular basis, parallel to determination of CD4 counts, by use of reverse-transcriptase–PCR (Roche).
Data on virus loads were available for 51 (22%) of 235 procedures. Lymphocyte immunophenotyping was performed on peripheral blood mononuclear cells isolated from whole blood by Lymphoprep density centrifugation (Nycomed). After undergoing 2 washing steps, the cells were immediately stained with the following fluorochrome-labeled antibodies (Becton Dickinson): anti-CD3, anti-CD4, anti-CD8, anti-CD19, antiCD56, and anti-CD25. Fluorescence-activated cell sorter (FACS) analysis was performed with CellQuest FACScan research software (BD Immunocytometry Systems). The absolute number of each T cell subpopulation (presented as the number of cells per microliter) was calculated by multiplying the fraction of cells for which staining revealed positive findings by the absolute lymphocyte count, which was derived from the differential WBC count. All the obstetric and gynecologic surgical procedures that we performed were standard procedures at our teaching hospital. The surgical techniques did not undergo significant changes during the 10 years reviewed in our study. Fifty-six of the 62 cesarean sections that were performed were elective procedures done to prevent vertical transmission of HIV [6, 7]. Perioperative antibiotic prophylaxis involved standard regimens of cephalosporins or aminopenicillins combined with b-lactamase inhibitors. Such prophylaxis was administered during 68 (28.9%) of 235 procedures in the HIV-positive group and during 6 (2.6%) of 235 procedures in the HIV-negative control group. None of the patients in the present study died, and lifethreatening complications occurred in only 1 patient. For classification of the severity of the complications observed, we defined the following postoperative problems as “major complications”: fever (temperature, 138C for 148 h) requiring antibiotic therapy during the postoperative clinical period; the need to perform additional surgical procedures; severe anemia requiring blood transfusions; and disseminated intravascular coagulation. Each of these complications was associated with prolonged patient hospitalization. The “minor complications” included transient fever not requiring antibiotics; impaired wound healing not requiring surgical revision; anemia not requiring blood transfusions; urinary tract infection; and development of endometritis and lochiostasis after obstetric procedures. The statistical significance of the differences between the mean values was calculated by Student’s t test. Differences between proportions were calculated by use of either the x 2 test or, where applicable, Fisher’s exact test. A multivariate logistic regression model was used to identify possible independent risk factors for postoperative complications. All statistical analyses were performed by use of SPSS software, version 10.0 (SPSS). HIV/AIDS • CID 2002:34 (15 March) • 823
RESULTS Complication rates according to HIV status. We retrospectively evaluated and compared the incidence of postoperative complications among HIV-positive patients with that among HIV-negative control patients. The mean patient age on the day of surgery was 29.7 years for the HIV-positive women and 30.9 years for HIV-negative women. Because the number of induced abortions in HIV-positive women was larger than the number of induced abortions in available control patients, HIVnegative women who had undergone curettage for incomplete or missed abortions were included in this control group. For 84 (36%) of 235 procedures, the HIV-infected patients were taking antiretroviral drugs at the time of the operation. The mean duration of HIV infection was ∼4 years. The modes of HIV infection were as follows: history of injection drug use (in 50 [28.9%] of 173 patients), transmission through heterosexual sexual activity (50 [28.9%]), exposure to HIV in an area of endemicity (primarily sub-Saharan Africa; 34 [19.6%]), history of injection drug use plus exposure through heterosexual sexual activity (20 [11.6%]), and other or unknown sources (19 [11%]). Most of the treated patients with HIV infection were asymptomatic. At the time of surgical intervention, HIV disease stage was determined according to Centers for Disease Control and Prevention (CDC; Atlanta) classification [15]; 148 patients (63%) had CDC stage 1 HIV disease, 50 (21.3%) had CDC stage 2 disease, and 21 (8.9%) had CDC stage 3 disease. For 16 patients (6.8%), CDC HIV disease stage was not exactly definable. The overall rate of complications following surgery was substantially increased for HIV-infected patients, compared with patients in the control group (44 complications [18.7%] per 235 procedures vs. 16 complications [6.8%] per 235 procedures). For HIV-positive patients, the majority of complications were associated with more-extensive abdominal operations, such as abdominal hysterectomy and cesarean section (figure 1). This difference is statistically significant (OR, 3.2; 95% CI, 1.7–5.8; P ! .0001). The general complication rate was higher in association with curettage procedures (table 1); it was more or less equal in all other categories of surgical procedures. Major complications occurred after 33 (14%) of 235 surgical interventions performed for HIV-positive patients, compared with 8 (3.4%) of 235 interventions performed for matched control patients. The difference between frequencies of complications in the HIV-positive group and those in the HIVnegative control group was also statistically significant (OR, 4.6; 95% CI, 2.1–10.3; P ! .0001). Again, the complication rate was highest in association with abdominal surgery (OR, 5.9; 95% CI, 2.2–15.4; P ! .0001) and curettage (OR, 3.8; 95% CI, 0.76–55; P p .1). Figure 1 shows that most complications were major. Minor postoperative complications occurred with approximately the 824 • CID 2002:34 (15 March) • HIV/AIDS
same frequency in HIV-positive women and HIV-negative women (11 complications [4.7%] per 235 procedures vs. 8 complications [3.4%] per 235 procedures). Obstetric surgery. Because postoperative complications occurring among HIV-infected women after childbirth are a major topic of interest, we evaluated patient outcomes after vaginal deliveries that involved surgical procedures. It has been shown elsewhere that cesarean section is associated with a higher rate of postoperative maternal morbidity among HIVinfected women, compared with that noted among HIV-negative women [11, 13]. In contrast to these findings of a higher rate of maternal morbidity after cesarean section, we did not see a worse outcome for HIV-infected mothers following episiotomy performed during spontaneous vaginal delivery. The rate of complications after this procedure was equal in the group of HIV-infected women and the control group. Perioperative antibiotic prophylaxis. Perioperative prophylaxis with different standard antibiotic regimens was provided to HIV-positive patients during 68 of 235 operations. Fifty-three of these 68 surgical interventions were abdominal surgeries. Prophylactic antibiotics were provided during 6 of 235 surgical procedures (all of which were abdominal operations) performed on HIV-negative patients. These HIV-negative patients were presumed to have an elevated risk of infection. None of the 6 HIV-negative patients developed postoperative complications, but 24 of the 68 HIV-infected patients who were receiving antibiotic therapy had complications. Among HIVinfected patients, CD4 cell counts were almost equal for patients with and without complications (mean CD4 cell count, 428 cells/mL vs. 440 cells/mL, respectively). The patterns of complications were also similar for the group of HIV-positive patients who were receiving antibiotic therapy and the group that was not receiving such therapy. Complication rates according to immunologic status. We also investigated how the occurrence of postoperative complications, examined both by type and collectively, correlated with patient immune status at the time of surgical intervention. Absolute CD4 cell counts or CD4 cell percentages, as well as CD4/CD8 ratios, were used as surrogate markers and were available for 164 of 235 surgical procedures. Parallel data on virus loads were only available for 51 procedures, because we did not begin measuring this parameter until 1995. As a general rule, after stratification of patients on the basis of the surgical procedures performed, we found lower CD4 cell counts and decreased CD4/CD8 ratios among patients who had complications. However, most of these differences failed to reach statistical significance. A statistically significant correlation between the complication rate and the CD4 cell count was seen only for patients who underwent abdominal surgery. Patients who had general complications after abdominal surgery had lower CD4 cell percentages in total lymphocyte counts than
Figure 1. Postoperative complications (major and minor) among HIV-positive women (HIV-pos.) versus HIV-negative women (HIV-neg.), by type of procedure performed.
did patients who underwent other types of surgery (mean, 24.1% vs. 30.4%; P p .01) (table 2). A similar trend was found with regard to the patient virus load at the time of surgery. The mean virus load was 10,200 copies/mL at the time of surgery for the 16 patients with complications, whereas it was 4700 copies/mL for the 35 patients without postoperative problems. For the patients who underwent abdominal procedures, the virus load at the time of surgery was 10,200 copies/mL for the 16 patients who had complications versus 5000 copies/mL for the 29 patients who did not. Again, this difference between the means was not statistically significant. Complication rates and current ART. We also analyzed the postoperative outcome for patients who were receiving ART, compared with those who were not receiving ART. We were surprised that the 84 patients who were receiving ART tended to have more complications than those who were not. The overall rate of complications for the treated patients was 26.2%, compared with 14.6% for the untreated patients (OR, 2.08; 95% CI, 1.07–4.04; P p .036). For major complications, the rate was 21.4% versus 9.9%, respectively (OR, 2.47; 95% CI, 1.17–5.21; P p .019). Both differences were statistically significant. The rates of minor complications in the 2 patient groups were nearly equal (4.8% for treated patients vs. 4.6% for untreated patients). The majority of the 84 treated patients were
given zidovudine monotherapy, which was the standard treatment at that time. The remainder received a fairly wide range of drug combinations, including highly active ART (HAART) regimens. The small numbers of patients studied precluded a meaningful statistical analysis of specific drug combinations. Multivariate analysis for identification of independent risk factors for postoperative complications. For the subset of operations associated with the most complications (abdominal surgery and minor procedures with an intrauterine component [n p 144]), multivariate analysis was performed to assess the effect of possible confounders that could have influenced patient outcome. We used a logistic regression model that included data on either CDC stage or CD4 cell count (variables were not independent), antibiotic prophylaxis, and ART. Virus load data was not included in the model, because such data were available for only 46 of the patients in this subset. Other possible confounding variables that did not show a correlation in univariate analyses were not included in the regression model. CD4 cell counts of !200/mL (OR 4.29; 95% CI, 1.21–15.21) and advanced stages of HIV infection (OR for CDC stage 2, 2.87; 95%, CI 1.13–7.29) were identified as independent risk factors for postoperative complications. Perioperative antibiotic prophylaxis was identified by univariate analysis as a significant risk factor for postoperative complications, but this finding was HIV/AIDS • CID 2002:34 (15 March) • 825
Table 1. Rates of postoperative complications among HIV-positive patients and HIV-negative control patients who underwent obstetric and gynecologic surgical procedures. No. (%) of postoperative complications among Surgical procedure, type of complication All (n p 235) a
Major
Fever for 148 h requiring antibiotic treatment
HIV-negative women
HIV-positive women
16 (6.8)
44 (18.7)
15.0
3.2 (1.7–5.8)
!.0001
8 (3.4)
33 (14.0)
16.7
4.6 (2.1–10.3)
!.0001
4 (1.7)
29 (12.3)
20.4
8.1 (2.8–23.5)
!.0001
x2 value
OR (95% CI)
P value
Further surgery necessary
5 (2.1)
8 (3.4)
0.7
1.6 (0.5–5.0)
.576
Blood transfusion
1 (0.4)
5 (2.1)
2.7
5.2 (0.6–45.4)
.208
Disseminated intravascular coagulation
0 (0.0)
1 (0.4)
0.98
8 (3.4)
11 (4.7)
0.494
Minorb
16.9
NC
.641
4.4 (2.1–9.4)
!.0001
Transient fever
9 (3.8)
35 (14.9)
Impaired wound healing
6 (2.6)
14 (6.0)
3.342
2.4 (0.9–6.4)
Lochiostasis
2 (0.8)
3 (1.3)
0.18
1.5 (0.2–9.1)
Endometritis
0 (0.0)
6 (2.6)
5.8
Anemia not requiring blood transfusion
1 (0.4)
1 (0.4)
0.00
Urinary tract infection
1 (0.4)
0 (0.0)
1.002
1.0
1.4 (0.6–3.5)
NC 1.0 (0.062–16.08) NC
.108 1.0 .028 1.0 1.0
Abdominal onlyb (n p 72) a
Major
6 (8.3)
25 (34.7)
14.8
5.9 (2.2–15.4)
!.0001
Major, with fever for 148 h requiring antibiotic treatment
3 (4.2)
21 (29.2)
16.2
9.5 (2.7–33.5)
!.0001
b
Minor
7 (9.7)
7 (9.7)
1.0 (0.33–3.01)
1.0
Minor, with transient fever
8 (11.1)
27 (37.5)
13.6
4.8 (2.0–11.5)
!.0001
13 (18.1)
32 (44.4)
11.7
3.6 (1.7–7.8)
1 (1.4)
7 (9.7)
4.8
Total b
Minor, with an intrauterine component (n p 72) NOTE. a b
0.000
7.65 (0.92–63.84)
.001 .063
NC, not computable.
Patients with 11 complication are counted only once; therefore, the total value of data provided for individual complications may not be the actual value. Data for patients who had both major and minor complications are included only in the entries for major complications.
not confirmed by the multivariate model. ART was not associated with the rate of postoperative complications in this subset of patients (table 3).
DISCUSSION Our clinical observations indicate that HIV-positive women experience more postoperative problems than do HIV-negative women. The number of operations performed on HIV-positive women—in particular, elective cesarean section and cervical surgery—has been increasing noticeably during the past 5 years. Therefore, these complications should be kept in mind by obstetricians and gynecologists who treat HIV-infected women. To systematically investigate the incidence of complications among HIV-infected women following obstetric and gynecologic surgery, we retrospectively evaluated patient outcomes associated with a total of 235 major and minor surgical procedures. The postoperative phase was often characterized by complications that had a fairly undramatic onset, a creeping clinical course, and slow clinical development. Protracted treatment was often necessary, and, overall, treatment of the com826 • CID 2002:34 (15 March) • HIV/AIDS
plications was successful. They were considered life-threatening in only 1 patient. Matching of HIV-negative control patients to HIV-positive patients was done on the basis of the surgical procedure performed and patient age. Additional matching by the surgeon who performed the procedure would have been desirable but was not feasible. During analysis, we did not note any obvious accumulations of complications attributable to particular surgeons either in our data set or in the general statistics regarding complications at our hospital. Therefore, even though we cannot rule out surgeon-dependent selection bias in the present study, we believe that it was not significant. When we analyzed the total number of postoperative complications for all types of procedures, we found a 13-fold greater risk for HIV-infected women, compared with HIV-negative control patients. For major complications, the risk was increased 14-fold for HIV-infected patients. When we analyzed the data in more detail, we found an 8-fold greater risk for fever requiring antibiotic treatment and a 14-fold greater risk for minor, transient fever. Procedures that required opening the abdominal cavity appeared to have the highest risk for HIV-
Table 2.
CD4 and CD8 cell values for patients with or without postoperative complications, by surgical procedure performed. Class of surgical procedure, postoperative complication status a
Patient CD4 and CD4 values, by complication severity Any, n c
CD4 cell percentage, mean CD4/CD8 cell ratio, mean Major, n c
CD4 cell percentage, mean CD4/CD8 cell ratio, mean Minor, n c
CD4 cell percentage, mean CD4/CD8 cell ratio, mean
c d
Minor (n p 43)
Cervical (n p 37)
Vulvar (n p 16)
Breast (n p 2)
Present Absent
Present Absent
Present Absent
Present Absent
Present Absent
Present Absent
Present Absent
26
37
1
2
4
39
0
37
1
15
1
1
437.9
502.6
439.0
508.4
711.0
489.5
376.8
575.0
—
358.2
707.0
678.7
112.0
187.0
24.8
28.6
24.1
30.4
43.0
17.0
22.3
28.5
—
26.5
40.0
32.0
19.0
15.0
0.6
0.8
0.6
0.8
1.3
1.4
0.6
0.8
—
0.7
1.0
1.3
0.4
0.2
131
136
d
d
22
41
1
2
4
39
0
37
0
16
1
1
456.3
496.4
474.9
482.4
711.0
489.5
376.8
575.0
—
358.2
—
680.4
112.0
187.0
24.9
28.4
24.8
29.4
43.0
17.0
22.3
28.5
—
26.5
—
32.4
19.0
15.0
0.6
0.8
0.6
0.8
1.3
1.4
0.6
0.8
—
0.7
—
1.3
0.4
0.2
5
Absolute CD4 cell count, mean
b
Endoscopic (n p 3)
28
Absolute CD4 cell count, mean
a
Abdominal (n p 63)
33
Absolute CD4 cell count, mean
b
All (n p 164)
159
4
59
0
3
0
43
0
37
1
15
0
2
334.8
494.4
241.8
495.9
—
563.3
—
556.5
—
358.2
707.0
678.7
—
149.5
24.2
27.9
20.3
28.3
—
25.7
—
28.0
—
26.5
40.0
32.0
—
17.0
0.7
0.8
0.6
0.7
—
1.4
—
0.8
—
0.7
1.0
1.3
—
0.3
Includes data for all procedures for which patient CD4 and CD8 cell counts were available. With intrauterine component. In total lymphocyte count. Statistically significant at P p .01.
Table 3.
Findings of logistic regression analysis of risk factors for postoperative complications. Percentage of procedures No. of procedures
With postoperative complications
Without postoperative complications
OR (95% CI), by univariate analysis
Adjusted OR (95% CI), by multivariate analysis
1
103
78.6
21.4
1a
1
2
27
51.9
48.1
3.42 (1.40–8.32)
2.87 (1.13–7.29)
3
6
33.3
66.6
1.84 (0.32–10.72)
1.86 (0.39–8.75)
57
84.2
15.8
1
1
Patient risk factor CDC HIV disease stage
CD4 cell count, cells/mL 1500
a
200–500
57
75.4
24.6
1.74 (0.68–4.41)
1.55 (0.59–4.10)
!200
16
50
50
5.33 (1.58–17.91)
4.29 (1.21–15.21)
No
83
81.9
18.1
1a
1
Yes
61
60.7
39.3
2.94 (1.38–6.28)
3.03 (0.88–10.43)
No
84
78.6
21.4
1
1
AZT monotherapy
35
65.7
34.3
1.91 (0.80–4.57)
1.36 (0.36–5.12)
HAART
25
64
36
2.06 (0.78–5.43)
1.48 (0.38–5.82)
Antibiotic prophylaxis
Antiretroviral therapy a
NOTE. AZT, azidothymidine; CDC, Centers for Disease Control and Prevention; HAART, highly active antiretroviral therapy. Included in this analysis is a subset of 144 operations performed on HIV-infected women, in which most postoperative complications occurred (abdominal surgery and minor procedures with an intrauterine component). a
Reference category.
infected women. Such procedures were associated with an almost 6-fold greater risk for major complications and a 19-fold greater risk for severe postoperative fever. Although postoperative morbidity did not reach statistical significance, it occurred more frequently in HIV-positive women than in HIVnegative women after curettage and comparable operations. All other procedures, apparently, were not associated with an elevated risk of postoperative complications. This observation is of particular importance with regard to HIV-infected women who undergo surgical procedures during childbirth. It recently has been shown that scheduled cesarean sections independently reduce the risk of vertical transmission of HIV [6, 7]. Official recommendations now suggest that HIV-infected mothers deliver their infants by means of this procedure [16, 17]. However, as reported elsewhere, HIV-positive women who undergo cesarean section have a 3–4-fold increased risk of severe postoperative complications [11, 13, 14]. In countries in which hygiene practices are poor and access to antibiotic therapy is difficult, this risk could be much higher—and eventually fatal—for such mothers [12]. On the other hand, HIV-positive women did not have a worse outcome than HIV-negative women following minor obstetric procedures, such as suturing of perineal tears or episiotomies. If, in the future, the rate of vertical transmission of HIV could be substantially reduced even further by use of combination ART 828 • CID 2002:34 (15 March) • HIV/AIDS
during pregnancy, delivery, or both, such recommendations should be reconsidered. The high rate of infectious complications among HIV-positive patients, despite the widespread use of standard antibiotic prophylaxis, was striking. Although the present study was not powered to prove the efficacy of perioperative antibiotic prophylaxis, this previously unreported observation was unexpected. In the data for the subset of operations for which we performed multivariate analysis, the unadjusted OR for complications among patients receiving perioperative antibiotic prophylaxis was 2.9 (95% CI, 1.38–6.28). One possible explanation for this finding could be that the proportion of patients with advanced-stage HIV infection (CDC stages 2 and 3) was significantly higher among patients who received perioperative antibiotics (OR 2.3; 95% CI, 1.06–4.98), thereby indicating a higher baseline risk for postoperative complications. Even though perioperative antibiotic prophylaxis was not confirmed to be an independent risk factor in our logistic regression model, this lack of confirmation should be carefully evaluated. It could indicate that standard antibiotic prophylaxis regimens used widely in general surgical and gynecologic procedures might not be sufficient to prevent infectious complications in HIV-infected women who have advanced stages of HIV infection. Further studies should investigate this question in more depth to define appropriate prophylactic antibiotic
regimens for HIV-infected women who undergo surgical procedures. Overall, our data on patient immunologic status at the time of the operation, as measured by CD4 and CD8 cell counts and virus load, showed some association, although not a statistically significant correlation, with the incidence and severity of postoperative problems. Patients with CD4 cell counts of !200/mL or with CD4 cells comprising !25% of the total lymphocyte count seemed to be at a high risk for complications, particularly after undergoing abdominal surgery. Patients with high virus loads also seemed to be predisposed to postoperative morbidity. The results of multivariate analysis of the subset of surgical procedures associated with the most postoperative complications (abdominal surgery and minor procedures with an intrauterine component) provided a clearer picture. CD4 cell counts of !200/mL and advanced-stage HIV infection (CDC stage 2), respectively, were confirmed to be independent risk factors in this model. Patients who belonged to these categories had 14-fold and nearly 3-fold increased risks of postoperative complications, respectively. It would have been desirable to include data on virus load in the logistic regression model as well. However, virus load data were available for only one-third of the patients in this subset analysis. Another objective of our study was to evaluate the impact of current ART on postoperative complications. At first it was surprising that the 84 patients who received ART tended to have more complications than the patients who were not receiving antiretroviral drugs. However, when we compared the mean CD4 cell count or CD4/CD8 ratio of the ART-treated patients with those of the 93 untreated patients, it became evident that the group receiving ART included patients with a lower baseline immunologic status. The mean CD4 cell count in the ART group was 420 cells/mL (CD4/CD8 ratio, 0.6), compared with 540 cells/mL (CD4/CD8 ratio, 0.9) in the nontreated group. These differences are statistically significant (P p .006, for the CD4 cell count, and P ! .001, for the CD4/CD8 ratio, respectively). This finding indicates that the ART regimens assessed in the study were not highly effective—at least, not in all cases. Multivariate analysis of a subset of our data, as previously discussed, showed that CD4 cell counts of !200 cells/ mL are an independent risk factor for postoperative complications. Therefore, we believe that modern HAART regimens that have proven efficacy as a result of their ability to restore CD4 cell counts should be able to lower the risk of postoperative morbidity. In particular, for elective operations, it seems desirable to optimize the immune function (in terms of CD4 cell counts) to the highest possible degree before surgical intervention commences. We performed this study to obtain a better estimate of the risk of postoperative morbidity among HIV-infected women
who undergo obstetric and gynecologic surgical procedures. The procedures associated with the highest risk of postoperative morbidity include both abdominal surgery and such relatively minor interventions as intrauterine curettage. We were able to demonstrate a correlation between the immune status of the patient, as measured by standard surrogate markers, and the occurrence of postoperative complications. Other independent risk factors could not be identified from a set of possible confounders for postoperative morbidity. We conclude that, for HIV-infected women, every indication for such surgical procedures—in particular, for those that are elective—should be thoroughly balanced against the considerably elevated risk for postoperative morbidity. Because the significance of this study is limited by its retrospective design, a prospective and multicentric study could better evaluate the incidence and the severity of postoperative complications among HIV-infected women. The need to perform obstetric and gynecologic procedures on HIV-positive women is likely to increase in the future, and the aforementioned type of study should be inaugurated to develop risk-reduction strategies for these patients.
Acknowledgments
We thank Melinda Morgan and Paul Castle, for critical reading of the manuscript, and Irene Krienke, for expert technical assistance.
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