Ravinder Kaur Sachdeva

Profile of hematological abnormalities of Indian HIV infected individuals

BackgroundHematological abnormalities are a common complication of HIV infection. These abnormalities increase as the disease advances. Bone marrow abnormalities occur in all stages of HIV infection.MethodsTwo hundred HIV infected individual were screened for hematological abnormalities from March 2007–March 2008. Absolute CD4 cell count analysis was carried out by flowcytometry. Depending on the results of the primary screening further investigations were performed, like iron studies, hemolytic work up, PNH work up and bone marrow evaluation. Other investigations included coagulation profile, urine analysis, blood culture (bacterial, fungal, mycobacterial), serology for Epstein Barr virus (EBV), Cytomegalovirus (CMV), Hepatitis B and C, and Parvo B19 infection.ResultsThe most common hematological abnormality was anemia, seen in 65.5% (131/200) patients. Iron deficiency anemia was seen in 49.2% (/200) cases while anemia of chronic disease occurred in 50.7% (/200) cases. Bone marrow evaluation was carried out in 14 patients out of which staging marrow was performed in 2 cases of non-Hodgkins lymphoma (NHL) and did not show any bone marrow infiltration. In remaining12 cases bone marrow was done for evaluation of pancytopenia. Among patients with pancytopenia 50% (6/12) showed granulomas (4 were positive for AFB, 2 were positive for fungal cryptococci), 25% (3/12) showed hemophagocytosis. There was a strong negative correlation between anemia and CD4 counts in this study. Thrombocytopenia was seen in 7% (14/200) cases and had no significant correlation with CD4 counts. No patient had absolute neutrophil count (ANC) < 800 cells/μL. No case of coagulation abnormalities was found.ConclusionAnemia in HIV patients can be a good clinical indicator to predict and access the underlying immune status. Patients should be investigated for hematological manifestations and appropriate steps should be taken to identify and treat the reversible factors.

Gene Polymorphisms in CCR5, CCR2, CX3CR1, SDF-1 and RANTES in Exposed but Uninfected Partners of HIV-1 Infected Individuals in North India

Repeated exposure to human immunodeficiency virus (HIV) does not always result in infection. Understanding the mechanisms that give protection against progressive infection with HIV may help in the development of a vaccine. In order to determine the influence of host genetic factors on HIV resistance, we studied 35 exposed but uninfected (EU) partners of HIV-1 infected individuals for polymorphisms in multiple chemokine and chemokine receptor genes and compared the results with those for 75 HIV-1 seronegative normal healthy controls (HC) and 50 HIV infected controls. There was no association between CCR5-Δ32, CCR2-64I, CX3CR1-280 M, CX3CR1-249I, SDF-3′A, RANTES-28G and RANTES-403A polymorphisms and susceptibility against HIV in our cohort of EU individuals. An increased frequency of SDF-1 3′A and RANTES-403A genotypes was present in EU individuals but the difference was not statistically significant when compared to healthy and HIV infected controls. These observations suggest that mechanisms other than genetic mutations of these genes might be responsible for resistance to HIV infection in these individuals.

Short Communication: Oxidative Stress in HIV-Infected Individuals: A Cross-Sectional Study

HIV infection increases the oxidative stress process, and antiretroviral combination therapy increases protein oxidation and preexistent oxidative stress. The latter induces production of reactive oxygen species. Lipid peroxidation (LPO) is a means of determining oxidative stress. There is also a deficiency of glutathione in HIV infection. Persistent oxidative load leads to an accelerated rate of consumption of glutathione (GSH). This study measured LPO and GSH levels in plasma of HIV-infected individuals with or without therapy and compared these with healthy controls. One hundred HIV-infected individuals and 30 healthy controls were included in the study. LPO and GSH levels were measured in plasma according to previously described methods. The mean level of LPO in HIV-infected individuals was 0.7 +/- 0.1 micromol/ml (range, 0.5-0.9 micromol/ml), whereas the mean LPO level in controls was 0.3 +/- 0.1 micromol/ml (range, 0.2-0.4 micromol/ml). The mean LPO levels were significantly higher in HIV-infected individuals as compared to healthy controls (p value <0.0001). The mean GSH level in HIV-infected individuals was 0.06 +/- 0.01 micromol/ml (range, 0.03-0.08). The mean GSH level in healthy controls was 0.09 +/- 0.01 micromol/ml (range, 0.05-0.1). The mean glutathione level in HIV-infected individuals was significantly lower in compared to healthy controls (p value < 0.0001). There was a significant positive correlation between absolute CD4 cells and GSH levels (rho = 0.182, p = 0.045). There is increased oxidative stress in HIV-infected patients. Whether supplementation with antioxidants will reduce this oxidative stress is still unknown.

Adverse drug reactions to nonnucleoside reverse transcriptase inhibitor-based antiretroviral regimen: a 24-week prospective study.

Background: Few studies have addressed the issue of adverse drug reactions with non-protease inhibitor (PI)-based antiretroviral therapy (ART) in resource-constrained settings. We studied prospectively the incidence of adverse drug reactions with generic ART among our patients. Methodology: A total of 100 HIV-infected individuals were recruited. Patients received nevirapine (NVP) or efavirenz (EFV) with lamivudine (3TC) and zidovudine (ZDV)/stavudine (d4T). They were followed for 6 months for evidence of adverse drug reactions. Results: The mean CD4 count was 114.09 ± 60.07 cells/mm3 (range, 12-232 cells/mm 3). Transient gastrointestinal symptoms were most frequent. Fourteen individuals (12 receiving ZDV/d4T, 3TC, NVP and 2 receiving ZDV/d4T, 3TC, EFV) developed skin rash. Among patients receiving NVP, 25.7% developed grade 1 hepatotoxicity. Three patients had numbness in both lower limbs. Among those individuals who received EFV, 32.3% individuals had central nervous system (CNS) symptoms in the form of insomnia, vivid dreams, dizziness, and drowsiness. Conclusion: As the developing world increasingly uses generic ART, the clinician must be constantly vigilant for treatment-related adverse events.

Human Immunodeficiency Virus (HIV) gag Antigen-Specific T-Helper and Granule-Dependent CD8 T-Cell Activities in Exposed but Uninfected Heterosexual Partners of HIV Type 1-Infected Individuals in North India

Repeated exposure to human immunodeficiency virus (HIV) does not always result in HIV infection, and several cohorts of HIV-exposed but uninfected (EU) individuals have been described. We studied T-helper and granule-dependent cytotoxic T-lymphocyte (CTL) activities in a group of 30 EU partners of HIV type 1 (HIV-1)-infected individuals. HIV-1-specific helper-T-cell activity was studied by measuring the levels of interleukin 2 (IL-2) produced by peripheral blood mononuclear cells (PBMCs) and the granule-dependent CTL activity by measuring the intracellular levels of perforin and granzyme B expression in CD8+ T cells after stimulation with gag p24 antigen. Elevated IL-2 production by PBMCs after p24 stimulation occurred in EU individuals. The levels of perforin and granzyme B expression in CD8+ T cells were also higher among EU individuals than among healthy controls. HIV-specific helper-T-cell and granule-dependent CTL activities inversely correlated with the time since the last unprotected sexual exposure in these individuals. In our cohort, activation of T-helper and granule-dependent CTL activities against HIV might be due to unprotected sexual contact. These results indicate that HIV-1-specific T-cell responses could play a role in protection against acquiring infection in this cohort of EU individuals.

Effect of non-nucleoside reverse transcriptase inhibitors on cytokine chemokine and immunoglobulin profiles in serum and genital secretions of HIV-infected women.

Non-protease inhibitor-based antiretroviral therapy (ART) is widely accepted as first-line ART in developing countries. Although reverse transcriptase inhibitor-based regimens have been studied in the peripheral blood, no studies have analyzed alterations in cytokine and chemokine levels, together in peripheral blood and genital secretions. Forty HIV-infected women with CD4 cell counts <200 cells/mm(3), asymptomatic, with no genital tract infection, willing to participate in the study, and adhere to ART were enrolled. Cervicovaginal lavage (CVL) was collected in the mid-cycle phase of menstrual cycle. Patients were initiated with reverse transcriptase-based antiretrovirals. Repeat sampling was performed at 24 weeks. Cytokines and chemokines were measured using ultrasensitive ELISA kits. Viral load declined to undetectable levels in 29 patients in the blood and in 33 cases in the CVL. Proinflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha, interleukin-6 [IL-6], IL-1beta) in the serum and CVL showed a significant decrease in mean levels after therapy. IL-2 levels increased significantly whereas IL-12 and (IFN-gamma decreased in both compartments. Mean levels of IL-4 and IL-10 decreased significantly in the serum. There was direct correlation between serum and CVL levels of IL-2 and IL-10. IL-10 had a negative correlation with CD4% at baseline and 6 months of therapy. Mean levels of all alpha- and beta-chemokines decreased in serum after therapy. In CVL, mean levels of MIP-1alpha, RANTES, and IL-8 reduced and SDF-1alpha increased significantly (P value <0.001). Serum levels of all the cytokines, except IL-2, and all chemokines prior to therapy, were significantly higher than healthy controls. In CVL, mean levels of TNF-alpha, IL-6, IL-1beta, IL-12, IFN-gamma, IL-10, RANTES, and IL-8 were significantly higher, whereas IL-2, MIP-1alpha, and MIP-1beta were significantly lower than healthy controls. The mean levels of proinflammatory cytokines and chemokines significantly decreased in serum and CVL after therapy, possibly due to reduced viral load.

Tuberculosis is the leading cause of lymphadenopathy in HIV-infected persons in India: Results of a fine-needle aspiration analysis

Abstract HIV infection is associated with a number of opportunistic infections and malignancies frequently involving the lymph nodes. Lymphadenopathy may occur at any stage of HIV infection. We aimed to determine the utility of fine-needle aspiration cytology in evaluating the causes of lymphadenopathy in HIV-infected individuals. Three hundred HIV-infected individuals with lymphadenopathy were included in the study. Fine-needle aspiration (FNA) was performed on peripheral or deep-seated lymph nodes. The material was used for cytological examination using May–Grunwald–Giemsa and haematoxylin and eosin staining. Special stains such as modified Ziehl–Neelsen staining for acid-fast bacilli and periodic acid-Schiff staining for fungi were also performed. The mean age of the study group was 35.0 ± 8.0 y (range 13–74 y). The median CD4 count was 152 cells/μl. Out of the 300 FNA reports, acid-fast bacteria were reported in 130 and cytological findings indicating mycobacterial infection in a further 43 patients. Cryptococcosis was reported in 4 individuals, histoplasmosis in 2 and aspergillosis in 1. Reactive hyperplasia was seen in 89 individuals. Lymphoma was noted in 7 individuals and suppurative inflammation in 5. In conclusion, tuberculosis is the predominant cause of lymphadenitis in HIV-infected individuals in India, especially in those with low CD4 cell counts.

Lamivudine-Induced Skin Rash Remains an Underdiagnosed Entity in HIV A Case Series from a Single Center

Background: Hypersensitivity reaction to antiretroviral treatment (ART) poses potential threats in maintenance of treatment. Lamivudine (3TC), is rare to cause rash. We are reporting 23 cases of 3TC-induced rash. Methods: An observational study conducted in the antiretroviral treatment center of a tertiary care hospital of North India from Feb 2009–Dec 2013 to record 3TC-induced rash. These were then recommended to start ART without 3TC and were followed up at 1-, 2-, and at 4-week intervals to monitor the toxicity, if any, with alternate therapy. Results: We observed 3TC-induced skin rash in 23 HIV-infected individuals (0.7%), out of 3213 HIV-infected individuals initiated on first line ART (zidovudine [ZDV]/tenofovir [TDF] + 3TC +nevirapine [NVP]/efavirenz [EFV] during the study period of 5 years [Feb 2009–Dec 2013]). The mean age of these 23 individuals was 37.5 ± 12.8 (17-60) years. Lamivudine rash was more common in women than men (F = 19, M = 4), with an overall mean age of 37.5 ± 12.8 (17-60) years. It was generalized, erythematous, maculopapular eruptions associated with intense itching with no associated mucosal involvement. Lamivudine was substituted with TDF in 19, didanosine (ddl) in 3 and abacavir (ABC) in 1 individual. Mean duration of follow-up is 11.1 ± 12.8 (3-42) months. CD4 count was repeated at 3 months and showed significant improvement (P = 0.002). Conclusion: Lamivudine-induced rash was found at a frequency of 0.7%. The correct and early recognition that the rash is due to 3TC, would save unnecessary substitution to a different class of drugs.

Effects of Lifetime History of Use of Problematic Alcohol on HIV Medication Adherence

Background: The effects of previous alcohol abuse on antiretroviral therapy (ART) adherence have been less studied. Materials and Methodology: Participants were randomized to a 3-month group intervention or an individual-enhanced standard-of-care condition and assessed over 6 months. Individual assessment at baseline, 3, and 6 months was done; interviews included lifetime history of problematic alcohol use. Results: A total of 80 HIV-positive individuals on ART were recruited. In all, 35% of participants reported a history of problematic alcohol use, 37% had a detectable viral load, 55% were nonadherent, and 24% reporting skipping medication in the previous 3 months. There was no association between a history of problematic use and an adherence at any time point, that is, at baseline (t = −.7, P = .47), midpoint (t = −.39, P = .69), and 6-month follow-up (t = −1.2, P = .23). Conclusion: Results suggest that a history of problematic alcohol use may not impact ART adherence.

Effect of antiretroviral therapy on hemoglobin A2 values can have implications in antenatal beta-thalassemia screening programs

Abstract Background: Raised hemoglobin-A2 (HbA2) is the diagnostic hallmark of beta-thalassemia trait (βTT). Diagnostic difficulties may arise in HIV-positive patients on antiretroviral therapy (ART). We compared the effect of various antiretroviral drugs on HbA2 levels. We attempted to determine which drugs elevate HbA2 levels causing a false-positive diagnosis of βTT and correlate the findings with red cell indices. Methods: A retrospective analysis of the records of an antenatal thalassemia screening program was carried out for 78 HIV-positive adults (70 antenatal women and 8 husbands) to study the effect of antiretroviral drugs on HbA2 levels. Three had βTT; 20 treatment-naïve subjects constituted controls. The effects of zidovudine (36 cases), stavudine (7 cases), and tenofovir (12 cases) were evaluated. High-performance liquid chromatography was done for HbA2 levels. Values of 3.5–3.9% were borderline and ≥ 4% with hypochromic microcytosis was considered to be βTT. Results: Twenty individuals not on ART had normal HbA2%. Three patients had βTT and showed hypochromic microcytosis despite being on zidovudine. Fourteen of 55 patients on treatment (25.5%) had borderline HbA2 values (mean 3.7%): 11 were on a zidovudine-based regimen and 3 on a stavudine-based regimen. One patient on zidovudine had 4.1% HbA2 with normal Hb and severe macrocytosis (MCV 128.5 fl), leading to a false suspicion of βTT. All patients on tenofovir had normal HbA2. Hematological parameters, including mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and HbA2 levels were increased due to antiretroviral drugs zidovudine and stavudine. Conclusion: Treatment-naïve subjects and those on tenofovir showed no effect on HbA2 levels compared with zidovudine and stavudine. A proportion of patients on zidovudine or stavudine had borderline elevated HbA2 levels, which could lead to a false impression of βTT.