Possibilities of surgical treatment of patients coinfected with HIV/tuberculosis

• Elena A. Borodulina
• Rogozhkin P.V.
• Viacheslav V. Piskun

Abstract

Aim - to determine the effectiveness of surgical treatment in patients with HIV/tuberculosis comorbid pathology.

Material and methods. The percentage of operations in patients with HIV-infection was 4.4% (25 operations) out of 572 radical lung resections performed for pulmonary tuberculosis. To assess the effectiveness of the surgical methods, 2 comparison groups were formed: the 1^st - a group of 23 operated patients, the 2^nd - a group of 25 patients without surgical treatment.

Results. When determining the type and volume of surgical intervention in patients with HIV-infection, low-traumatic operations were preferable. Surgical treatment was prescribed as planned, with the participation of an infectious disease doctor in treatment, after a course of antiretroviral therapy had been carried out in the preoperative period and a CD4⁺-T-lymphocyte count of >200 cells/pl had been achieved. The operations performed were 100% effective, there were no postoperative complications and mortality. MBT was found in all situations in the resected area of the lung. Half of the identified mycobacteria was multidrug and broadly resistant. There was no postoperative mortality. In the 1^st group, 2 years after surgery, almost 70% were removed from the register. In the group without surgery, 2 years after therapy, only 4% were removed from the register (p=0.00001).

Conclusion. A comparative analysis revealed that surgical treatment reduces duration of treatment and increases effectiveness.

Keywords:tuberculosis, HIV, surgical treatment

HIV-infection is a factor that has a negative impact on the epidemiology of tuberculosis. According to the World Health Organization (WHO) and other sources since 2006 and at present, the number of cases of tuberculosis with concurrent HIV-infection has increased by 2.9 times [1, 2]. This is due to the fact that the possibility of tuberculosis contraction in HIV-positive individuals is 100 times higher than in HIV-negative people [3, 4]. Increasing number of comorbid TB diseases/HIV is associated with high mortality [5-11]. The disease affects mainly people of young and working-age [5, 10, 11]. The search for optimal methods of treatment is an actual problem [12, 13]. Surgical treatment is one of the methods in complex treatment that allows increasing the effectiveness of treatment [14-17]. The surgical methods of treatment effectiveness for patients with tuberculosis combined with HIV-infection is still to be studied [18, 19].

Material and methods

in 2016-2017, 572 radical lung resections were performed for pulmonary tuberculosis, while the proportion of operations in patients with HIV-infection was 4.4% (25 cases). There was held an analysis of surgeries in patients with pulmonary tuberculosis combined with HIV-infection. To assess the effectiveness of the inclusion of surgical methods in treatment, two comparison groups of patients were formed: 1 - group of 23 patients who were operated, 2 - group of 25 patients without surgical treatment. Efficacy was evaluated by the criterion of deregistration after recovery.

Results

the gender and age characteristics of patients, social aspects and the method of detecting pulmonary tuberculosis in the comparison groups were studied. In the 1^st group, there were 11 men (47.8%), 12 women (52.2%). In the 2^nd group, there were 12 (52.2%) men and 11 (42%) women, respectively (χ²=0.08; p=0.7817). The average age of the 1^st group was 32.6±1.52 [95%; confidence interval (CI) 25.48-35.79] and the 2^nd group was 33.16±1.36 [95%; CI 30.34; 35.98] (U=280.5; p=0.893). In terms of social characteristics and the methods of detecting pulmonary tuberculosis, the comparison groups did not have significant differences. In both groups, most patients were unemployed, 15 (65.2%) patients in 1^st group, and 15 (60.0%) patients in 2^nd group. A history of drug abuse was observed in 8 (34.8%) patients in the 1^st group and in 10 (40.0%) patients in the 2^nd group. 5 (21.7%) patients in 1^st group and 5 (20.0%) patients in 2^nd group stayed in a correctional labor institution. The groups are comparable for comparative analysis.

In the 1^st group, tuberculosis was detected using annual large picture frame photoroentgenography 9 (39.1%), during examination at the AIDS center 6 (26.1%), during complaints in the general medical network 5 (21.7%), during examination at a tuberculosis dispensary as contact 3 (13.0%).

In the 2^nd group, tuberculosis was detected using annual large picture frame photoroentgenography 8 (32.0%), during examination at the AIDS center 7 (28.0%), during complaints in the general medical network 6 (24.0%), during examination at a tuberculosis dispensary as contact 4 (16.0%).

The main method for detecting tuberculosis in both groups was annual large picture frame photoroentgenography.

In most cases, 11 (47.2%) patients in 1^st group and 14 (56.0%) patients in 2^nd group, HIV-infection was diagnosed before pulmonary tuberculosis. The index did not have significant differences between groups, but in the first group there were more patients and amounted to 56% χ²=0.32 (р=0.57).

HIV-infection was detected during examination for tuberculosis in 8 (34.8%) patients from the 1^st group and 7 (28.0%) patients in the 2^nd group, all these patients were tested for HIV for the first time χ2=0.26 (p=0.6125). Much less often patients were already registered with a phthisiatrician with a diagnosis of pulmonary tuberculosis, in the 1^st group there were 4 (17.4%) people and in the 2^nd group - 4 (16.0%) people χ2=0,02 (р=0.8972).

CD4-lymphocyte count was determined in all patients at the time of admission. In the 1^st group 459.09+46.41 [95% CI 362.84; 555.33], in the 2^nd -429.64±47.07 [95% CI 332.49; 526.79] (p=0.476).

14 (60.9%) patients received antiretroviral therapy before surgery. Before the operation, the level of CD4⁺-T-lymphocytes averaged 459.09±46.41 cells/ml.

The characteristics of the clinical forms of tuberculosis in the groups had no significant differences.

According to the forms of the tuberculous process, the patients were diagnosed with: tuberculoma in the 1^st group - 19 (82.6%), in the 2^nd group - 19 (76.0%), fibrous-cavernous pulmonary tuberculosis 3 (13%) and 4 (16.0), χ2=0.08 (р=0.7719), cavernous tuberculosis 1 (4.4%) and 2 (8.0%) χ2=0.27 (р=0.6015) (see Table 1).

Table 1. Clinical forms of tuberculosis in patients of the studied groups

Note. ABS - absolute; DST - drug susceptibility testing.

* - including DST analyzes obtained from surgical material.

Pulmonary tuberculoma was detected to be the main form χ2=q.32 (p=0.5733). According to the characteristics of the prevalence of the tuberculous process, decay cavities in the operated lung among all patients were χ2=0.17 (p=0.6828) equally in the majority of those observed in the groups. Fibrous-cavernous pulmonary tuberculosis was limited in volume of the lesion within one lobe of the lung. This allowed them to apply surgical treatment, there were a minimum number of such patients.

After the operation, a macroscopic examination of the surgical material was carried out; the presence of a cavity of destruction in tuberculoma (or tuberculomas) was observed in 12 of 19 cases (63.1%). At the time of registration, mycobacterium tuberculosis (MBT+) was detected in 11 (47.8%) patients in the 1^st group and 12 (48.0%) in the 2^nd group, χ2=0.0001 (p=0.9904). At the same time, in all these cases, mycobacteria in sputum were detected by bacterioscopy, molecular-genetic methods (GeneXpert MTB/RIF), on liquid nutrient media with automatic registration BACTEC MGIT and inoculation on a standard Lowenstein-Jensen medium. Among patients with a positive MBT test, a drug susceptibility test (DST) of mycobacterium tuberculosis (MBT) was performed. Multidrug resistance or extensive drug resistance was detected in 11 (47.8%) patients of the 1^st group and 9 (36.0%) of the 2^nd group χ²=0.69 (p=0.4064).

There were no significant differences in the groups in terms of clinical forms of pulmonary tuberculosis, bacterial excretion and results of drug sensitivity.

All patients before the operation received specific anti-tuberculosis therapy according to standard antibacterial chemotherapy regimens. The decision to prescribe surgical treatment was made after the completion of the intensive phase of chemotherapy; patients with multidrug resistance and extensive drug resistance took specific antibacterial drugs for at least 6 months before surgery.

When analyzing opportunistic pathology (see Table 2), one of the most frequently diagnosed diseases was chronic viral hepatitis type C (n=15; 65.2% in the 1^st group and n=15; 60.0% in the 2^nd group) χ²=0.14 (p=0.7091). Chronic viral hepatitis type B was not detected in patients of the 1^st group, in the 2^nd group it was detected in 1 (4.0%) patient χ²=0.94 (p=0.3324). Chronic bronchitis was in 2 (8.7%) patients in the 1^st group and in 3 (12.0%) patients in the 2^nd group χ²=q.14 (p=0.7081). Alcoholism in the 1^st group was observed in 6 (26.1%) patients, in the 2^nd group it was also observed in 6 (24.0%) patients χ²=0.03 (p=0.8675). There were 5 (21.7%) active drug addicts in the 1^st group, in the 2^nd - 7 (28.0%). χ²=0.25 (p=0.6168). There were no differences in concomitant and opportunistic diseases in the groups, all diseases are associated with social factors, which in most cases determine the presence of HIV-infection.

Table 2. Concomitant diseases and addictions in patients in comparison groups

The structure of the performed radical operations in the first group of patients is shown in Table 3.

Table 3. Types of surgical interventions in operated patients (n=23)

Note. ABS - absolute.

Patients underwent the following operations: lung resection (within 1-2 segments) - 15 (65.2%) people; polysegmental lung resection - 5 (21.7%) people; lobectomy - 1 (4.3%) person; bilateral resection (within 1-2 segments on each side) - 2 (8.7%) patients. A total of 23 operations were performed. In patients with a diagnosis of fibrocavernous tuberculosis (3 people), the following operations were performed: 1 lobectomy, 1 polysegmental resection, 1 lung resection within 1-2 segments. A patient with cavernous pulmonary tuberculosis (1 person) underwent polysegmental resection. Major surgeries (combined resection of the lung, bilobektomiya, pneumonectomy) in this group of patients were not performed. Intraoperative and postoperative complications were absent, all patients were discharged in satisfactory condition. Postoperative wounds healed by primary intention, there was no slow expansion of the lung and residual cavities. The operations were effective in all patients. The average hospital stay for HIV-infected patients was 52±1.1 bed days and did not have statistically significant differences from the indicator among all operated patients. 5 (21.7%) patients who underwent a long stage of preoperative chemotherapy stayed in hospital for more than 70 days. Postoperative complications among all operated patients in 2016-2017 were <1%. Postoperative mortality in 2016-2017 was absent.

After 2 years (≈24 months) of observation, an analysis of the effectiveness of treatment of patients in the comparison groups was performed (see Table 4).

Table 4. Treatment results after 2 years («24 months)

In the 1^st group, 16 (69.6%) patients were removed from the dispensary registration with recovery, χ²=22.51 (p=0.00001), which is significantly more often compared with non-operated patients. 4 (17.4%) patients were transferred to the 3^rd group of dispensary registration and continue to be registered, reactivation of the tuberculous process in the postoperative period was observed in 1 (4.3%) patient, death as a result of progression of HIV-infection was also observed in 1 (4.3%) patient.

The results of treatment of patients in the 2^nd group differed significantly: 1 (4.0%) patient was removed from the dispensary registration with recovery, 9 (36.0%) patients were transferred to the 3^rd group of dispensary registration and continue to be registered, progression of the tuberculous process was observed in 3 (12.0%) patients, death due to progression of HIV-infection was observed in 3 (12.0%) patients. 7 (28.0%) patients continue to be in the former dispensary registration group, in the 1^st group there were no such patients χ²=7.54 (p=0.0060).

Conclusion

Surgical treatment was prescribed as planned, with the participation of an infectious disease doctor in treatment, after a course of antiretroviral therapy was carried out in the preoperative period and a CD4+-T- lymphocyte count of >200 cells/pL was achieved. When determining the type and volume of surgical intervention in patients with HIV-infection, preference was given to low-traumatic operations. The operations performed were 100% effective, there were no postoperative complications and mortality.

MBT was found in all situations in the resected area of the lung. Half of the identified mycobacteria had multidrug and extensive drug resistance. There was no postoperative mortality. CD4-lymphocyte counts in all operated patients were >400 cells/μL. All patients received antiretroviral therapy before surgery and completed the main course of chemotherapy.

During treatment of patients with comorbidity of HIV-infection and tuberculosis, the use of surgical methods of treatment has shown its effectiveness.

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