Association of Hematological Profile of Human Immunodeficiency Virus-Positive Patients with Clinicoimmunologic Stages of the Disease

INTRODUCTION

Human immunodeficiency virus (HIV) infection is a state of profound immunodeficiency, encompassing a spectrum of disease ranging from acute syndrome seen with primary infection, prolonged asymptomatic state, to an advanced disease or full-blown acquired immunodeficiency disease syndrome (AIDS). Disorders of hematopoietic system are common but often overlooked complications of HIV infection which manifest at any stage of the disease and include anemia, leukopenia, thrombocytopenia, hemophagocytic syndrome, AIDS-related lymphoma, and rarely thromboembolism.

Due to the lack of laboratory technologies in resource-limited countries, WHO guidelines suggest the use of simple tests such as hemoglobin (Hb) <12 g/dl and total lymphocyte counts (TLC) <1,200/cumm as indicators for initiation of antiretroviral therapy (ART).^[1] Thus the objective of this study was to study the hematologic profile of HIV-positive patients and its association with the clinicoimmunologic stage of the disease.

MATERIALS AND METHODS

The study population included 187 consecutive HIV-positive patients attending the ART clinic at Dr. Ram Manohar Lohia Hospital, New Delhi. The inclusion criteria included HIV-positive patients, symptomatic as well as asymptomatic, diagnosed by enzyme-linked immunosorbent assay (ELISA) method according to the National AIDS Control Organization (NACO) guidelines. Exclusion criteria included any primary hematologic disorder (such as thalassemia, leukemia, etc.), chronic renal/liver disease, receiving cytotoxic/immune modulating chemotherapy, pregnant and lactating women.

The study population was divided into three categories based on the clinicoimmunologic status of the patients:

HIV infection: No symptoms/signs of clinical AIDS, CD4 count > 200/μl.

Immunological AIDS: With CD4 < 200/μl, no symptoms/signs of clinical AIDS but CD4 count < 200/μl.

Clinical AIDS: Patients with any AIDS defining illness.

The patients in the study group were divided into two groups:

Group A (ART-Y): Patients receiving ART.

Group B (ART-N): Treatment naåve patients not on ART.

Cut-off values were defined to calculate the prevalence of different hematologic values. Anemia (Hb < 10 g%), thrombocytopenia (platelets < 1.5 lakh/mm³), leucopenia (white blood cells (WBC) <4,000/mm³). The hematologic profile was then statistically analyzed for prevalence of abnormalities and their association with the clinicoimmunologic stage of the disease, as well as between treated and nontreated groups (group A and group B). The group or categorical data were tested for statistical significance using the Chi-square test and Z-test. The difference was reported as significant if P < 0.05.

OBSERVATIONS AND RESULTS

A total of 187 patients were included in the study population. There were 134 male and 53 female patients at a male-female ratio of 2.53:1. Age of the patients ranged from 18 to 66 years. The study population was divided into two groups. The distribution of patients in group A and group B in different categories is shown in Table 1.

DISCUSSION

Disorders of the hematologic system are common in HIV-infected patients. The hematologic manifestations of HIV are varied and prevalent throughout the course of the disease. Anemia is a frequent complication of HIV infection. In a study by Patwardhan et al., ^[2] who investigated the hematologic profile of 500 HIV patients, anemia was found in 30.8% of individuals. Our analysis showed a 40.1% prevalence of anemia, with a higher prevalence in patients not receiving ART compared to that in those receiving highly active antiretroviral therapy (HAART). Thus, the use of HAART results in decrease in the prevalence of anemia. In our study, the proportion of patients having a normal Hb (>12 g%) was significantly different in treatment and nontreatment groups. Only 20.93% patients who were not receiving any ART (group B) had Hb > 12 g%. However, this percentage was significantly higher, i.e. 42.57%, in group A, who were receiving HAART. This observation was also found in a previous study which included patients recruited to the EuroSIDA cohort.^[3]

However, in this study, the prevalence of anemia was still high (35.64%) in the treated group. This could be because of various drugs used for treatment of HIV and prophylaxis/treatment of opportunistic infections causing bone marrow suppression and anemia. This study also revealed an increase in the prevalence of anemia with progression of clinicoimmunologic stage of the disease, which is in accordance with previous studies.^[4,5]

Various studies have shown that anemia is an important factor in understanding the clinical course of HIV-infected patients.^[6] Sullivan et al., in their study reported that the incidence of anemia was strongly and consistently associated with progression of HIV disease as measured by diagnosis of AIDS defining opportunistic illness and measurement of CD4 count < 200 cells/μl. This association is most likely explained by the increasing viral burden as HIV disease progresses, which leads to cytokine-mediated myelosuppression and anemia.^[4] The results of a study by Mocroft et al., ^[3] showed that hemoglobin levels provided prognostic information independent of that provided by CD4 count.

In this study, normocytic normochromic anemia was the most common morphologic type of anemia, followed by microcytic hypochromic and the macrocytic, the rarest of all. A dimorphic picture was found in 13.88% of anemic patients in group A probably due to AZT-induced macrocytosis. These results are similar to those reported by other workers.^[2,5]

In our study, anemic patients on AZT therapy had mostly a macrocytic type of anemia. However, macrocytosis was also seen in patients who did not have anemia and who were on AZT therapy. Thus AZT-induced macrocytosis is not necessarily associated with anemia. More recent studies of combination ART have confirmed the relatively low incidence of severe anemia at low doses of AZT.^[7] In our study, most of the patients had normal platelet counts. Thrombocytopenia was seen in 3.74%, i.e. 2.95% in group A and 4.65% in group B. This was similar to the finding of Tripathi et al., and Patwardhan et al., ^[2,5] Thrombocytopenia occurred in all stages of the disease, with preponderance in early stages as well as in late stages of full-blown AIDS.

In this study, normal leukocyte count was most commonly seen in both the groups. Leukocytosis was seen in 6.93% of patients in group A and 12.79% in group B. This is similar to that observed in Patwardhan's study.^[2] The higher prevalence in group B, i.e., untreated patients, probably reflects an increase in leukocyte count secondary to various opportunistic infections that are more common in patients not receiving any antiretroviral or chemoprophylactic therapy. Patwardhan reported leukopenia in 15.47% of cases.^[2] Leukopenia was seen in a total of 5.88% of patients in this study with no significant difference with respect to clinical stage of the disease. It was, however, more common in group B, ART-N (8.14%) compared with those in the group A, ART-Y (3.96%). In total, 75% and 100% of leukopenic patients in group A and group B, respectively, had associated anemia. This observation is in accordance with that reported by Zon et al., ^[8] who described a considerable overlap in hematologic abnormalities, wherein 88% of granulocytopenic patients were found to be anemic.

Our study reported pancytopenia in 1.6% of patients. Eosinophilia is probably due to reaction to various parasitic infestations that are common in patients with HIV infection. Venous thrombosis was found in 0.53% of patients, i.e., one out of 187 patients. A center for disease control (CDC) study found the incidence of thrombosis to be 2.6 per 1,000 person years, which is significantly higher than expected in the general population.^[9] The hemophagocytic syndrome, a rare complication of HIV, was found in one patient in our study, thus giving a prevalence of 0.53%. This complication was associated with a CD4 of less than 200/μl.

CONCLUSION

This study of the hematologic profile of HIV patients reiterated the fact that affection of the hematopoietic system by HIV is common. The hematologic abnormalities are prevalent through all stages of the disease, and some of these may serve as indicators of clinical progression.