Incidence of tuberculosis among HIV infected individuals on long term antiretroviral therapy in private healthcare sector in Pune, Western India.

BACKGROUND: Despite rapid scale up of antiretroviral therapy (ART), Tuberculosis (TB) remains the commonest opportunistic infection and cause of death among HIV infected individuals in resource limited settings like India. Incidence of TB in individuals on ART in private healthcare sector in India is infrequently studied. METHODS: This retrospective cohort study conducted between 1st March 2009 and 1st March 2017 aimed to evaluate rate of incident TB in individuals initiated on ART at 3 private sector ART clinics in Pune, India. Individuals more than 12 years of age with ART duration of atleast 6 months were included. Patients were classified as having prevalent TB if they had a TB episode within the year prior to ART initiation or if they developed TB within 6 months of starting ART. Individuals who were diagnosed with TB after 6 months of starting ART were classified as incident TB cases. A recurrent episode of TB after treatment completion or cure of prevalent TB was also regarded as incident TB. Patients were classified as definitive TB if Mycobacterium tuberculosis was grown in culture from a biological sample or a positive rapid molecular test. Patients were classified as probable TB if there was radiologic evidence of TB in absence of confirmatory culture or PCR. RESULTS: 1904 patients with a median duration of follow up on ART of 57 (IQR = 32.0, 84.0) months were included. Of these, 182 developed incident TB (22% definitive TB, 38% recurrent cases). TB incidence at 6-12 months, 13-24 months, 25-60 months and > 60 months of ART was 24.32, 5.46, 2.54 and 0.75 cases per 100 person years respectively. Current time updated CD4 count < 500 cells/mm3 (p < 0.0001), virologic failure on ART (adjusted Hazard Ratio (aHR): 3.05 (95% CI: 2.094, 4.454), p < 0.0001) and receipt of ART without IPT (aHR: 8.24 (95% CI, 3.358, 20.204), p < 0.0001) were associated with higher risk of incident TB. CONCLUSION: Starting ART early in treatment naïve individuals, prompt detection of virologic failure on ART and providing IPT along with ART will be useful in reducing incident TB. Efforts from private sector are crucial in achieving Sustainable Development Goals set by Government of India and attaining the vision of a TB free India.

Cellular Immune Responses Against γ-Inactivated Antigen in the Recovered Cases of Kyasanur Forest Disease.

Kyasanur Forest Disease Virus (KFDV) is a tick-borne flavivirus that causes life-threatening hemorrhagic fever in humans with case fatality rates of 3-5%. Relatively little is known about the mechanism of its pathogenesis or host immune responses to KFDV infection. Here, we investigated KFDV-specific cellular immune responses in the recovered cases of Kyasanur Forest Disease (KFD). Peripheral blood mononuclear cells of the recovered KFD cases and healthy controls were exposed to γ-inactivated KFDV antigen ex vivo. The proliferation index was determined using an enzyme-linked immunosorbent assay-based lymphoproliferative assay. The frequencies of CD4+ and CD8+ T cells expressing intracellular interferon (IFN)-γ in response to stimulation with γ-inactivated KFDV antigen were determined using flow cytometry. A significant increase in lymphoproliferation and a high frequency of CD4+ and CD8+ T cells secreting IFN-γ against γ-inactivated KFDV antigen were found in the recovered KFD group compared to the healthy control group. In conclusion, the study indicated the generation of cellular immune responses in individuals who recovered from KFD and can be used as indicators of cellular immunity in KFD vaccine studies.

Two treatment strategies for management of Neurosymptomatic cerebrospinal fluid HIV escape in Pune, India.

Symptomatic cerebrospinal fluid (CSF) viral escape (sCVE) is reported in people with HIV, who are on ritonavir-boosted protease inhibitor (PI/r) containing antiretroviral therapy (ART). Management of sCVE includes performing genotypic HIV-1 resistance testing (GRT) on CSF and plasma HIV and changing ART accordingly. Neither GRT nor newer drugs (Dolutegravir and Darunavir/ritonavir) are routinely available in India. As a result, management of sCVE includes 2 modalities: a) ART intensification by adding drugs that reach therapeutic concentrations in CSF, like Zidovudine, to existing ART or b) Changing to a regimen containing newer boosted PI/r and integrase strand transfer inhibitor (INSTI) as per GRT or expert opinion. In this retrospective study, we report the outcomes of above 2 modalities in treatment of sCVE in Pune, India.Fifty-seven episodes of sCVE in 54 people with HIV taking PI/r-containing ART were identified. Clinical, demographic, laboratory and ART data were recorded. Forty-seven cases had follow-up data available after ART change including measurement of plasma and CSF viral load (VL).Of the 47 cases, 23 received zidovudine intensification (Group A, median VL: plasma- 290, CSF- 5200 copies/mL) and 24 received PI/INSTI intensification (Group B, median VL: plasma- 265, CSF-4750 copies/mL). CSF GRT was performed in 16 participants: 8 had triple class resistance. After ART change, complete resolution of neurologic symptoms occurred in most participants (Group A: 18, Group B: 17). In Group A, follow-up plasma and CSF VL were available for 21 participants, most of whom achieved virologic suppression (VL < 20 copies/mL) in plasma (17) and CSF (15). Four participants were shifted to the PI/INSTI intensification group due to virologic failure (plasma or CSF VL > 200 copies/mL). In Group B, follow-up plasma and CSF VL were available for 23 participants, most of whom also achieved virologic suppression in plasma (21) and CSF (18). Four deaths were noted, 2 of which were in individuals who interrupted ART.This is a unique sCVE cohort that was managed with 1 of 2 approaches based on treatment history and the availability of GRT. At least 75% of participants responded to either approach with virologic suppression and improvement in symptoms.

Occult medullary carcinoma of thyroid with lymph node metastases: a case report.

BACKGROUND: Occult thyroid malignancies presenting with secondary neck masses as the first clinical manifestation is well known. Although rare, medullary carcinoma serves a potential source for lymph node metastases. The characteristic cytomorphology of medullary thyroid carcinoma (MTC) should clinch the diagnosis. Further, fine needle aspiration cytology (FNAC) of the ultrasonography-detected occult nodules in thyroid serves as a useful preoperative diagnostic tool. CASE: A 22-year-old man presented with left-sided neck masses of 1 year duration. FNAC smears of the neck masses revealed cytomorphology characteristic of MTC. Ultrasonography of the thyroid led to ruling out the presence of an occult nodule and detected an 8-mm nodule in the left thyroid lobe. Ultrasound-guided FNAC of the nodule showed features similar to those with FNAC of the neck masses. Surgical resection of thyroid and neck masses further confirmed the diagnosis of a primary occult MTC with lymph node metastases. CONCLUSION: FNAC smears of lymph node masses showing the distinct cytomorphology of MTC should prompt suspicion for occult primary in thyroid. Ultrasound-guided FNAC of these occult nodules, if detected, further serves a diagnostic tool for accurate preoperative diagnosis when metastasis presents as the first clinical manifestation of an occult primary.

Strongyloidosis Hyperinfection Syndrome in an HIV-Infected Patient: A Rare Manifestation of Immune Reconstitution Inflammatory Syndrome.

Parasitic infections such as Strongyloides stercoralis and HIV have been reported to coexist, particularly in resource-limited settings such as India. In an immunocompromised host, S. stercoralis can progress to strongyloidiasis hyperinfection syndrome (SHS). However, SHS is not common in patients with advanced HIV disease. Immune reconstitution inflammatory syndrome (IRIS) developing after initiation of antiretroviral therapy (ART) can target multiple pathogens including S. stercoralis. The authors present here a 46-year-old HIV-infected female who was recently diagnosed with HIV-1 infection, started ART, and developed SHS. Her upper GI endoscopy revealed severe gastroduodenitis, and X-ray chest showed extensive bilateral pneumonitis. We could identify S. stercoralis in induced sputum and duodenal biopsy. We could also identify gut inflammation to restrict invading parasites. After receiving antihelminthic therapy, she showed improvement, a course of events that fit the diagnosis of unmasking S. stercoralis IRIS.

Discordant CSF/plasma HIV-1 RNA in individuals on virologically suppressive antiretroviral therapy in Western India.

Aim of this study was to estimate the prevalence of cerebrospinal fluid (CSF)/Plasma HIV-1 RNA discordance in virologically suppressed individuals presenting with incident neurologic symptoms.In this retrospective cohort study conducted between March 1, 2009, and March 1, 2017, HIV-1 infected adults exposed to atleast 12 months of antiretroviral therapy (ART) and having plasma viral load (VL) <1000 copies/mL (virologically suppressed) were included. Among these, individuals presenting with neurologic symptoms during follow-up were assessed for CSF/Plasma HIV-1 RNA discordance by measuring HIV-1 RNA in collected plasma and CSF samples. CSF/plasma HIV-1 RNA discordance was defined as either detectable CSF HIV-1 RNA (VL > 20 copies/mL) with an undetectable plasma RNA (complete viral suppression, VL ≤20 copies/mL) or CSF HIV-1 RNA ≥ 0.5 log10 higher than plasma RNA when plasma VL was between 20 and 1000 copies/mL (low-level viremia, LLV).Out of 1584 virologically suppressed patients, 71 (4.4%) presented with incident neurologic symptoms. Twenty out of 71 (28.2%) patients were diagnosed with CSF/Plasma HIV-1 discordance. Median plasma and CSF VL in patients with discordance was 120 [interquartile range (IQR): <20 to 332.5] and 4250 (IQR: 2550.0- 9615.0) copies/mL, respectively. All 9 individuals in which CSF HIV-1 genotypic resistance testing was done showed mutations that would compromise efficacy of prescribed ART regimen. Prevalence of CSF/plasma HIV-1 RNA discordance was higher among neurologically symptomatic patients with plasma LLV as compared with those with complete viral suppression (70% vs 11.8%, P < .001). The risk of discordance was also greater in patients who received protease inhibitor (PI) containing ART (P < .001) and those on ART regimens with central nervous system (CNS) penetration effectiveness (CPE) value <6 (P = .006).CSF/plasma HIV-1 RNA discordance indicates replication of HIV-1 that has adapted to the CNS or has developed antiretroviral drug resistance. Larger studies should be performed to study incidence of discordance in India. This will help in managing patients presenting with neurologic symptoms on suppressive ART with appropriate neuroeffective therapy.