Hitender Gautam

Epidemiology of opportunistic infections and its correlation with CD4 T-lymphocyte counts and plasma viral load among HIV-positive patients at a tertiary care hospital in India.

The study was conducted to find the correlation of CD4 counts and plasma viral load (PVL) with opportunistic infections (OIs) in HIV-positive patients. A total of 43 drug-naive patients enrolled in the study. Absolute CD4 counts and PVL were measured. On the basis of symptoms, sputum, stool, and blood samples were obtained for laboratory tests. Oral swabs were obtained from all the patients. Pneumocystis jiroveci pneumonia was found in 45.2% patients (odds ratio [OR] = 12.8 for CD4 counts ≤100 cells/ mm3 and 8.5 for PVL >4.0 log10 copies/mL). Pulmonary tuberculosis (TB; OR = 8.0 for PVL >4.0 log10 copies/mL) and streptococcal pneumonia (detected only with CD4 counts <50 cells/mm 3 and PVL >4.0 log10 copies/mL) were seen in 41.9% and 12.9% patients, respectively. Among patients with diarrhea, Giardia lamblia was detected in 31% patients (OR = 3.0 for CD4 counts ≤100 cells/mm3 and 4.0 for PVL >4.0 log10 copies/mL) and Cryptosporidium in 17.2% patients (OR = 1.8 for CD4 counts ≤100 cells/mm3 and found only with PVL >4.0 log10 copies/mL). Shigellosis and Clostridium difficile toxin was present in 13.6% patients and 6.8% patients, respectively.

Resistance-Associated Mutations in HIV-1 among Patients Failing First-Line Antiretroviral Therapy:

Thirty-five HIV-1 infected patients showing clinical and/or immunological failure to first line antiretroviral therapy (ART) according to WHO criteria were recruited from the ART center of Lok Nayak Hospital, New Delhi to detect the presence of resistance-mutations in reverse transcriptase (RT) and protease (PR) region of pol gene of HIV-1. Plasma viral load (PVL) was estimated. HIV-1 pol gene region encoding complete protease and reverse transcriptase (codons; 1-232 to 1-242) was reverse transcribed, followed by nested PCR. The PCR product was sequenced and analyzed. Plasma samples from 94.3% of patients with PVL >log10 3.0 c/mL could be amplified and analyzed. Virologic failure was detected in 65.7% of patients according to WHO criteria (PVL >log10 4.0). All patients were found to be infected with subtype C. One or more resistance-mutations were observed among 90.9% of study sequences. Nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations were seen among all patients, with M184V and thymidine analogue mutations (TAM) being most frequently detected (75.6% and 72.7%, respectively). Nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-mutations were detected in 63.6% of sequences, of which Y181C/I (47.6%), K103N (33.3%) and G190S (28.6%) are the most common. None of the sequences showed major protease inhibitors (PIs) resistance mutation. High prevalence of NRTI and NNRTI drug resistance mutations among the study participants warrants the use of genotypic resistance testing to prevent accumulation of resistance mutations, which would limit future treatment options.

Role of C-reactive protein in HIV infection: a pilot study.

Limited data on acute phase C-reactive protein (CRP) levels in human immunodeficiency virus (HIV) infection exist. The relationship of CRP with HIV was assessed in 119 HIV-positive patients and correlated with CD4 counts and mortality at 1 y. CRP was negatively correlated with CD4 counts with levels of CRP being highest in the group with CD4 counts below 200 cells/microL. It was an indicator of mortality and hence may serve as a useful and inexpensive predictor of HIV disease progression.

Use of surrogate markers to predict the HIV disease stage and time to initiate antiretroviral therapy in developing countries.

CD4 counting is the standard method for determining eligibility for antiretroviral therapy (ART) and HIV disease progression, but it is not widely available in developing countries. The aim of this study was to correlate the levels of β-2 microglobulin and total lymphocyte count (TLC) with CD4 counts for monitoring disease progression and identify patients who require ART. The authors measured CD4 T-cell counts, TLC, and β-2 microglobulin levels in 119 HIV seropositive patients. There was a significant negative correlation between CD4 counts and β-2 microglobulin levels and significant positive correlation between TLC and CD4 counts. Taking a TLC cutoff of ≤ 1600 and β-2 microglobulin levels ≥ 3.5 mg/l, the authors could identify 90.4% of patients with CD4 count ≤ 200 cells/µl. These assays may allow reduction in the annual number of CD4 cell evaluation and the cost associated with monitoring the immune status of HIV-positive patients.

CORRELATION BETWEEN BASELINE CD4 + T-LYMPHOCYTE COUNT AND PLASMA VIRAL LOAD IN AIDS PATIENTS AND THEIR EARLY CLINICAL AND IMMUNOLOGICAL RESPONSE TO HAART: A PRELIMINARY STUDY

The aim of this study was to determine the clinical, immunological and virological status of newly diagnosed AIDS cases and to monitor their clinical and immunological response to HAART after a minimum period of three months. Forty three drug naive AIDS patients were enrolled. The most common presenting complaints were weight loss (74.4%), cough (72.1%) and diarrhoea (67.4%). Mean baseline CD4 cell count was 112 +/- 60 cells/microL and mean baseline plasma viral load of 31 patients studied was 192,686 copies/mL. Baseline plasma viral load was higher among patients with lower baseline CD4 cell count. During follow-up, 80.8% patients showed clinical improvement, while a CD4 cell count increased by > or =50 cells/microL in 84.6% cases. Mean CD4 cell count increased from 126 +/- 16.6 cells/microL at baseline to 278 +/- 196.7 cells/microL.

Oral Thrush to Candidemia: A Morbid Outcome

A 35-year-old female living with AIDS presented with oral thrush 3 months after the initiation of antiretroviral therapy (ART). On investigation, it was found to be due to Candida albicans. She was started on fluconazole. After 4 months on ART, she presented with fever. Blood culture was performed. After 4 days, she expired due to septic shock. Two days after her death, C albicans strain was isolated from the blood culture which was similar to the C albicans strain (by DNA fingerprinting) isolated from oral thrush. Both strains of C albicans were found to be resistant to fluconazole by broth microdilution method. A high index of suspicion in high-risk patients along with early and aggressive management of the patient with antigen detection would go a long way in the management of these patients. Guidelines for treatment of candidiasis need to be re-evaluated, keeping in mind the increasing emergence of resistance to azoles and its effect on morbidity outcome.

Utility of Serum Neopterin and Serum IL-2 Receptor Levels to Predict Absolute CD4 T Lymphocyte Count in HIV Infected Cases.

A prospective study was carried out to evaluate the efficacy of serum neopterin and soluble IL-2 receptor (sIL-2R) concentrations in comparison to CD4 count to study the progression of HIV disease and monitor response to ART in HIV cases. One hundred newly diagnosed HIV seropositive subjects were recruited. CD4 counts were determined by FACS system. Serum neopterin and sIL-2R levels were measured using enzyme immunoassay. In our study, levels of neopterin and sIL-2R were significantly higher in subjects with CD4 <200 cells/μL (with S. neopterin levels of >25.1 nmol/L and sIL-2R levels of >47.1 pM as cutoff values for CD4 <200 cells/μL) compared to those in subjects with CD4 >200 cells/μL at baseline which indicate that these markers can be utilized for initiation of ART in HIV cases. The levels of these markers decreased significantly after initiation of ART. In patients with CD4 >200 cells/μL, these markers are helpful in predicting disease progression.

Epidemiology and Seroprevalence of Human Immunodeficiency Virus Type 2.

HIV-2 infection is detected sporadically mostly from the southern states of India. We did a retrospective analysis to find the seroprevalence of HIV-2 in and around Delhi. The study included all attendees of an integrated counseling and testing center (ICTC) from January 2004 to January 2009. As per NACO guidelines, samples showing positive results in three rapid tests were declared HIV-positive. Samples that were reactive for HIV-2 were further confirmed by Western blot assay. 8.8% (n = 1,938) of the clients were reactive for HIV-1, 0.03% (n = 6) were reactive for HIV-2 and 0.005% (n = 1) had HIV-1 and HIV-2 coinfection. Spouses of only 2 cases were tested, both resulting as nonreactive. History of travel or past stay to endemic states was present in 57% cases. The commonest risk factor revealed in them was sexual contact with commercial sex workers (86%). As such, seroprevalence of HIV-2 is very low but continued surveillance is needed for HIV-2 to understand the epidemiology and natural history of this complex human pathogen.

Use of total lymphocyte count to predict absolute CD4 count in HIV-seropositive cases.

We conducted an observational study to assess the use of total lymphocyte counts (TLC) alone and along with hemoglobin (Hb) as a predictor of CD4 count. A total of 103 antiretroviral therapy (ART)-naive HIV-1-infected patients were enrolled and divided in 2 groups (with CD4 count <200 cells/mm3 and CD4 count ≥200 cells/mm3). The TLC and Hb were performed by automatic full digital cell counter. CD4 count was determined by flow cytometry. Among the World Health Organization (WHO) clinical stages 2 and 3, in the cases with CD4 count <200 cells/mm3, 70.4% cases had TLC ≤1200 cells/mm 3, whereas 63% cases had TLC ≤1200 cells/mm3 + Hb ≤12 g/dL. In the cases with CD4 count >200 cells/mm3, 2% cases had TLC ≤1200 cells/mm3, whereas adding Hb ≤12 g/dL with TLC ≤1200 cells/mm3, none of the cases would require initiation of ART. TLC + Hb can be used to treat all HIV-infected patients with WHO stages 2 and 3 who have a TLC <1200 cells/mm3 + Hb ≤12 g/dL and to limit CD4 counts to patients who are symptomatic but have TLC + Hb values other than TLC <1200 cells/mm3 + Hb ≤12 g/dL.

Concurrent Cryptococcal and Pneumocystis Pneumonia along with Pulmonary Tuberculosis in an HIV-Positive Patient: Lessons Learned for Early Management

Case: We are presenting a 50-year-old patient of pulmonary tuberculosis, on anti-tuberculosis therapy (ATT) for last 2 months who presented with fever, cough, breathlessness, anorexia, and weight loss. The case was found to be HIV reactive. His sputum sample showed Candida albicans and Pneumocystis jirovecii. Fluconazole and cotrimoxazole + sulphamethoxazole were added. The index case did not respond to the treatment and his clinical condition started to deteriorate and he developed headache, vomiting, and dysphagia. Repeat sputum sample and cerebrospinal fluid (CSF) showed Cryptococcus neoformans which was found to be sensitive to Amphotericin B. Amphotericin B was added to the treatment and patient clinically responded to treatment. In conclusion, emphasis should be given to correct etiological identification, allowing appropriate treatment and decreasing the morbidity and mortality in these patients as concomitant opportunistic infections may cause diagnostic problems.