Clinical profile of human immunodeficiency virus patients with opportunistic infections: A descriptive case series study.

BACKGROUND: Human immunodeficiency virus (HIV) virus, causative agent in acquired immunodeficiency syndrome, is fast becoming a major threat in the Indian subcontinent, with an estimated 3.7 million persons being infected with HIV. HIV infection is complicated by various opportunistic infections (OIs) such as tuberculosis (TB), candidiasis, herpes zoster, Pneumocystis jirvoceii, cytomegalovirus (CMV) etc., This study carried out to know the clinical profile of HIV patients with OIs.
METHODS: A case series study was carried out at a tertiary care hospital in Bellary, Karnataka, India. A hospital based case series study was conducted among 164 HIV patients with OIs admitted to various wards as well as attending outpatient department at Vijayanagara Institute of Medical Sciences Hospital, Bellary during Jan 2013 to Nov 2013. Both primary and secondary data was collected to gather information on clinical profile. The statistical tests used were descriptive statistics and independent t test.
RESULTS: Among 164 patients, 29.3% were females and 68.3% males. High proportions of patients were observed in 28-37 years of age group and heterosexual route was the most common mode of transmission. TB (50%) is the most frequent OI followed by candidiasis (49%), pneumocystis (16%) and others. The mean CD4 cell count in TB was 237.02/mL and in candidiasis 189.07/mL. Low values were observed in promyelocytic leukemia (18.10/mL), CMV (18.5/mL) and in toxoplasmosis (73.1/mL).
CONCLUSIONS: Respiratory system was the most common system involved by OIs and most of patients with OIs had CD4 T cell count below 200/mL, whereas there were no patients in the study with counts above 500/mL.

INTRODUCTION

People with advanced human immunodeficiency virus (HIV) are vulnerable to infections called “opportunistic infections” (OIs) because organisms take advantage of the opportunity offered by a weakened immune system. Since the beginning of the HIV epidemic, OIs have been recognized as common complications of HIV infection.[123] OIs cause substantial morbidity and hospitalization, necessitate toxic and expensive therapies, and shorten the survival of people with HIV infection.[45] A decrease in CD4+ count is at least partially responsible for the profound immunodeficiency that leads to various OIs in HIV-infected persons.[6]

The introduction of antiretroviral therapy (ART) has dramatically reduced the incidence of OI among HIV-positive people who have received ART; however, around the world, millions of people living with HIV in resource-poor communities have no access to ART.[1] At present, the initiation of primary prophylactic therapies for OIs is based chiefly on the absolute CD4+ count, which has been shown to be an excellent predictor of the short term overall risk of developing acquired immunodeficiency syndrome (AIDS) among HIV-infected patients.[7] The relative frequencies of specific opportunistic diseases may vary in different countries and even in different areas within the same country.[8] The identification of such pathogen is very important for HIV and AIDS case management.

Human immunodeficiency virus causes progressive impairment of the body's cellular immune system leading to increased susceptibility to tumours and infections, and the fatal condition is known as AIDS.[9] The unique feature in the pathogenesis of HIV/AIDS is that the primary target cell for HIV is immune cells bearing the CD4 marker at their surface. With HIV infection, there will be a gradual decrease of human immune cells bearing CD4 antigen receptor, the most important being T helper cells (CD4 T cells), B lymphocytes, macrophage and natural killer cells leading to development of wide varieties of OIs that is, severe infections induced by agents that rarely cause serious diseases in immune competent individuals. In this way AIDS related mortality and morbidity, which is significantly higher in number as compared to other diseases, is actually due to OIs rather than HIV itself.[10] In the era of effective ART, diagnosis and treatment of OIs is an integral part of this treatment strategy because some OIs regimens (for e.g., antituberculosis drugs) and ART regimen should not be administrated at the same time to prevent drug induced toxicity and mortality and morbidity due to immune reconstitution inflammatory syndrome.[11] CD4 cell count is the best validated predictor of the likelihood of developing OIs. Besides, it has great utility in clinical consideration of HIV disease classification and AIDS definition, assessment of prognosis and designing of clinical trials, for e.g., decision about initiation of ART/prophylaxis.[12] There are wide range of OIs affecting different system, for example, respiratory tract infection, gastrointestinal tract infection, urinary tract infections, sexually transmitted infection and disseminated infection.[13]

Once the standard value of CD4 count and the OIs incidence rate at that stage is obtained, this can be used as a model for other resource limited settings (where CD4 count facilities are not available) to take decision about the initiation of ART in relation to CD4 status were done in a local setting with limited sample size but specific studies aimed at making standard profile of different OIs according to CD4 were lacking.[14]

Hence, this study is conducted with a general objective to explore the relationship between CD4 level and different types of OIs which may be helpful for the development of guidelines regarding the initiation and monitoring of ART/prophylaxis. Furthermore, the result of the findings will be helpful in the prognosis of different OIs in HIV/AIDs patients.

METHODS

Descriptive study was carried out during January 2013 to November 2013 at medicine Out Patient Department, medicine wards and ART centre of a tertiary care hospital. Human immunodeficiency virus positive patients older than 18 years with OIs were the study subjects. The exclusion criteria were - Patients harbouring OIs who are immune-suppressed because of causes other than HIV; non-consenting patients; seriously ill patients from whom data collection was impossible. Total of 164 HIV positive patients with OIs were considered for the study and the sampling technique adopted was non probability purposive sampling.

Primary data was collected from patients by interview technique and secondary data from case records after obtaining written informed consent. Primary data: Includes basic socio demographic and other information. Secondary data: Includes data related to clinical findings and investigation reports. Data was analyzed by computing proportions, mean and t-test; by using microsoft excel and SPSS 20.0 trial version downloaded from www14.software.ibm.com.

Data was collected after getting informed consent from the patient. Confidentiality of the patients’ detail was maintained.

RESULTS

The current study revealed that the maximum number of patients who had OIs were in the age group of 28–37 years (45.7%), followed by the age group 18–27 years (27.4%) and 38–47 years (21.3%). No patients were found in the age group above 60 years. There was higher proportion of males (68.3%) as compared to females (29.3%). The male to female ratio was 2.3:1. The HIV patients with OIs were less educated that is, 27.4% were illiterate and 39% had primary education. Only 11.6% subjects had education of college. Most of the patients, who harboured OIs, were unskilled labourers (39%), followed by semiskilled (14.6%), skilled (10.9%) business, professional and others constituted 35%.

Of all the cases maximum number of HIV positivity with OIs were seen in the married group (54.3%), followed by people who were unmarried (20.7%), who were separated (17.7%) and least among widows (7.3%). Heterosexual mode of transmission was the commonest mode of transmission, accounting for 84.7% [Table 1].

Table 1

Sociodemographic characteristics of study subjects

In the current study as depicted in Table 2, the most common symptoms at presentation were fever (78%), loss of appetite (76%), weight loss (74%), cough (58%), where as diarrhoea was seen in only 18%of the cases [Table 2].

Table 2

Distribution of study subjects based on symptoms

Among patients who presented with history of fever, 88.5% of them had fever of more than 1-month duration. Among patients who presented with history of weight loss, 62.2% of them had loss of body weight of more than 10%. Among patients who presented with history of diarrhoea, 83.3% of them had diarrhoea of more than 1-month duration. Among patients who presented with history of cough, 91.4% of them had cough of more than 1-month duration.

On general examination, the most common signs found were emaciated built (73%), fever (60%), tachycardia (94%), tachyopnea (62%) and pallor (76%). Genital lesions and skin lesions constituted 18% [Table 3]. Among patients with OIs, respiratory system was more commonly affected (56%) followed by nervous system (26%), skin (15%), genitals (10%). Only 5–6% of patients had abnormality in chorionic villus sampling and abdomen [Table 4]. It is evident from the present study that TB is the most of frequent OIs accounting for 50% of all OIs, followed by candidiasis in 49% of cases [Table 5].

Table 3

Distribution of study subjects based on clinical signs on general examination

Table 4

Distribution of study subjects based on systemic examination

Table 5

Distribution of study subjects based on type of opportunistic infections

In this study, 65% of the patients with OIs had CD4+ T-Cell counts below 200/μL, where as there were none with counts above 500/μL [Table 6]. The mean CD4+ cell count in TB was 237.72/μL and in candidiasis 189.07/μL. Low values were observed in promyelocytic leukemia (18.10/μL), cytomegalovirus (18.5/μL). Statistically significant association was found between CD4 count and TB, candidiasis, cryptosporidiosis, isosporiosis, and strongyloidiasis [Table 7].

Table 6

Distribution based on CD4 T cell

Table 7

Comparison of CD4 cells among opportunistic infections

DISCUSSION

In the present study, majority of patients were in the age group of 28-37 years. This is consistent with other studies reported from India and abroad.[1516] It was observed that the frequency of OI was highest in the sexually active age group of society. This indicates a trend of young and productive generation being affected; a reflection of the devastating effects India will face as the this work force is affected.

The incidence of OI was significantly high in patients who were less educated and this directly indicates the impact of level of education on the transmission of the disease, as education is directly related to the level of awareness.[17]

The commonest mode of transmission was heterosexual (84.7%) followed by others, as heterosexual transmission remains the commonest mode since other sexual practices being very uncommon in this part of the world.[18] This study also found that a small proportion of transmission attributed to blood transfusion/needle prick as observed in other studies.[1920]

In this study, it was found that fever was the most frequently occurring symptom present in 78% of the cases followed by loss of appetite, weight loss and cough. These findings are consistent with studies reported in literature.[2122] Numerous OIs occur in HIV infected patients due to down regulation of the immune system. In the present study, it was found that TB was the most frequent OI accounting for 50% of all infections followed by candidiasis in 49% of cases. Similarly in a study of Sharma[23] and Vajpayee,[24] TB was most common OI followed by candidiasis, whereas contradictory to this in a study of Patel,[25] Giri,[26] and Singh,[27] candidiasis was the most common followed by TB.

Human immunodeficiency virus-TB co infection is a serious problem worldwide but especially of concern in India where background rates of TB is highest in the world.[28] In India, the most common OI among people with HIV infection is pulmonary TB.[2729] Hence respiratory system is most commonly involved as observed in our study.

The mean CD4 count was low for TB in our study compared to western data. Candidiasis in our study occurred at a wide range of CD4 levels; but mean CD4 count was189.07. Compared to our study, studies by Moore et al. and Crow et al. showed that the mean CD4 count was much lower for candidiasis. The mean CD4 count for cryptosporidiosis, isosporidiosis, and strongyloidosis in our study was very similar to the mean CD4 count of Moore et al.[4]

CONCLUSION

In our set up most frequent OIs are accounted by TB and candidiasis and there is a direct correlation between the values of CD4 count and the severity of the OIs, hence indicating the level of immunity and the severity of the disease.