Investigation of apoptotic markers among human immunodeficiency virus (HIV-1) infected individuals.

BACKGROUND & OBJECTIVES: Apoptosis causes a decline in the counts of uninfected bystander CD4+ T cells in HIV infection. The rate of disease progression of HIV infection is considered to be faster in the developing countries. The present study was carried out to investigate certain markers for apoptosis in immunopathogensis of disease in HIV infected south Indian population. METHODS: Soluble Fas (sFas) antigen and Fas ligand levels in plasma samples from 39 antiretroviral treatment naïve patients was estimated and compared with T cell subsets and HIV-1 viral load. RESULTS: The mean sFas antigen levels among controls and the CDC A, B and C clinical stages were 2.77, 3.08, 3.26 and 3.28 ng /ml respectively, higher though not significantly among HIV-1 infected individuals compared to controls. The mean sFas ligand levels in CDC A, B and C stages were 0.138, 0.125 and 0.117 ng/ml respectively were higher (P<0.001) than controls (0.073 ng/ml) and positively correlated with total lymphocyte % (r=0.43, P =0.007). sFas antigen levels were negatively correlated with total WBC count (r=-0.34, P=0.04), CD4% (r=-0.4, P=0.01) and CD4:CD8 ratio (r=-0.37, P=0.02). There was an increase in plasma levels of sFas antigen and Fas ligand over time in asymptomatics. INTERPRETATION & CONCLUSION: The high levels of sFas antigen and Fas ligand seen in HIV infected individuals suggest increased activation and apoptosis of T cells, due to constant stimulation of the immune system by inter-current infections of HIV infected individuals in south India.

Chemokine profile among human immunodeficiency virus-1 (HIV-1) infected individuals from southern India.

BACKGROUND & OBJECTIVE: Individuals infected with HIV-1 have higher levels of chemokine producing cells compared to uninfected individuals. It is important to know the changes in chemokine levels associated with rate of progression of disease. There is a paucity of information on the plasma chemokines in HIV-1 infected individuals from India. We therefore carried out this study to estimate the levels of three chemokines namely macrophage inflammatory protein alpha (MIP1alpha), MIP1beta and RANTES, in relation to disease status in HIV-1 infected individuals and compared with uninfected individuals. METHODS: RANTES and MIP1alpha were estimated using ELISA in 114 HIV-1 infected and 30 controls, whereas MIP1beta was estimated in 101 HIV infected individuals only and 30 controls. The values were compared to the T cell subsets, HIV-1 viral loads and plasma cytokines (interferon gamma and interleukin-10). RESULTS: Compared to controls the mean MIP1alpha and RANTES level among the HIV-1 infected individuals was higher while MIP1beta level was lower in HIV infected individuals except CDC C groups. There was a significant positive correlation for MIP1á with HIV-1 viral load and IFNgamma, for MIP1alpha with viral load and IL10. There was a significant negative correlation between MIP1alpha with CD4 count and CD4: CD8 ratio and MIP1beta with CD4 count and CD8 count. There was a negativecorrelation between RANTES values and CD8 per cent. INTERPRETATION & CONCLUSION: In conclusion, our study showed a significantly higher level of beta chemokines in south Indian HIV-1 infected individuals compared to controls. These beta chemokines may have the inhibitory effect on HIV-1 only during the initial period and with the progression of disease this inhibitory effect wanes as shown by the positive correlation of beta chemokines with HIV-1 viral load.

Disseminated histoplasmosis.

OBJECTIVE: To study the clinical features and natural history of disseminated histoplasmosis(DH) in India. METHODS: We retrospectively analyzed the data obtained from the in-patient medical records of adults (age > 13 years) diagnosed to have DH during the period from January 1989 to December 1999. DH was diagnosed when histologically compatible intracellular organisms were present or Histoplasma capsulatum was obtained in culture from the extrapulmonary sites. RESULTS: Nineteen patients (18 male and 1 female) were diagnosed to have DH. Diabetes mellitus and HIV infection were the most common co-morbid conditions. Weight loss, fever and oropharyngeal ulcers were the commonest symptoms. Physical signs included hepatosplenomegaly, oropharyngeal ulcers and lymphadenopathy. The diagnosis was confirmed by histopathology and/or culture from the following sites: bone marrow, adrenal gland, lymph node, oropharyngeal ulcers, rectal mucosa and skin. Two patients were treated with Amphotericin B, 6 with various azoles and 3 had Amphotericin B followed by various azoles. Among the eleven treated, 7 were cured, 2 improved, 1 had a relapse and 1 patient died. CONCLUSION: DH is not uncommon in India and should be considered in the diagnosis of patients with prolonged fever, weight loss, oropharyngeal ulcers, hepatosplenomegaly, lymphadenopathy and adrenal enlargement. Correct diagnosis and treatment leads to a favourable outcome.

Aetiology of prolonged fever in antiretroviral-naïve human immunodeficiency virus-infected adults.

BACKGROUND: Prolonged fever is a common symptom among human immunodeficiency virus (HIV) infected individuals, and is usually due to a cause that is easily treatable. Limited data are available regarding the causes of fever in HIV-infected Indian patients. In this paper, we have profiled the causes of prolonged fever in a cohort of HIV-infected Indian patients and have developed suitable algorithms to assist in an early diagnosis. METHODS: From February 1997 to October 1998 (20 months), 100 HIV-infected patients (age > 12 years) were evaluated for 100 episodes of prolonged fever (fever > 100 degrees F for more than 2 weeks in outpatients and > 3 days in inpatients). Patients with terminal acquired immunodeficiency syndrome (AIDS) were excluded. Patients were evaluated on the basis of the symptoms associated with prolonged fever and investigated according to pre-existing algorithms. RESULTS: Among such episodes of fever, infection was the major cause and included tuberculosis, especially the extra-pulmonary and disseminated forms (69%), cryptococcosis (10%) and Pneumocystis carinii pneumonia (7%). Other causes included bacterial pneumonia, amoebic liver abscess, disseminated histoplasmosis and cerebral toxoplasmosis. Patients were naïve for antiretroviral therapy and did not receive prophylaxis for opportunistic infections. The diagnostic yield of ultrasound of the abdomen (85%), fine-needle aspiration cytology of enlarged lymph nodes (75.6%) and bone marrow trephine biopsy (41.6%) were found to be high in our study. CONCLUSIONS: Tuberculosis is the commonest cause of prolonged fever in HIV-infected adults in India. Non-infectious causes were not seen in this series. We have suggested an algorithmic approach for establishing the cause of fever in these patients. In situations where laboratory evaluation does not reveal a cause for prolonged fever, a therapeutic trial with antituberculous therapy in selected patients is justified.

Increased number of CCR5+ CD4 T cells among south Indian adults probably associated with the low frequency of X4 phenotype of HIV-1 in India.

BACKGROUND & OBJECTIVE: The shift of the human immunodeficiency virus (HIV) from nonsyncytium inducing strains (NSI/R5) to syncytium inducing strains (SI/X4) seen in subtype B infections during progression to acquired immunodeficiency syndrome (AIDS) is less frequently reported in subtype C. NSI and SI strains differ in the co-receptor they utilize to infect a T-cell. We postulated that a larger pool of CD4 T cells expressing CCR5 would be present among individuals in the Indian population. To validate this hypothesis, we estimated the percentage of CD4 cells expressing CCR5 or CXCR4 molecules among healthy south Indian adults and HIV infected individuals. METHODS: HIV-1 infected and uninfected adult volunteers, belonging to the four southern states of India with Tamil/Malayalam/Kannada or Telugu as their spoken language were prospectively recruited. A two colour flowcytometry examination of the blood sample was done using the following monoclonals; anti-CD45 (FITC)/CD14 (PE), anti IgG1 (FITC)/IgG2a (PE), anti-CD3 (FITC)/CD4 (PE), anti-CD3 (FITC)/CD8 (PE), anti-CD4 (FITC) and anti CCR5 (PE) or anti CXCR4 (PE). RESULTS: In the healthy population (n = 30) studied, 24.6 per cent of CD4 T cells expressed CCR5 and the percentage of CD4 T cells expressing CXCR4 was 80.4. Among the HIV infected individuals (n = 51) the percentage of CD4 T cells expressing CCR5 and CXCR4 was 26.8 and 78.7 per cent respectively. INTERPRETATION & CONCLUSION: The percentage of CD4 cells expressing CCR5 and CXCR4 in both the HIV uninfected and infected adults was significantly higher in the south Indian population than in the West. The larger pool of CCR5 positive CD4 cells probably allows for the R5 HIV strain to have a replication advantage over X4 HIV strains. This may explain the lack of shift in the viral phenotype during disease progression and also the perceived rapid progression of the disease in India compared to the West.