Suniti Solomon

Multiple NF-κB sites in HIV-1 subtype C long terminal repeat confer superior magnitude of transcription and thereby the enhanced viral predominance.

Background: Viral evolution of HIV-1 is dynamic and moving towards a higher order of replicative fitness. Results: HIV-1 subtype C acquires an extra (4th) NF-κB site to achieve a higher degree of transcription and in turn enhances its replicative fitness and preponderance. Conclusion: Subtype C with an extra NF-κB site adopts a novel strategy of strengthening its promoter to gain fitness. Significance: Learning how the new strains could impact viral prevalence, pathogenesis, and disease management strategies is critical. We demonstrate that at least three different promoter variant strains of HIV-1 subtype C have been gradually expanding and replacing the standard subtype C viruses in India, and possibly in South Africa and other global regions, over the past decade. The new viral strains contain an additional NF-κB, NF-κB-like, or RBEIII site in the viral promoter. Although the acquisition of an additional RBEIII site is a property shared by all the HIV-1 subtypes, acquiring an additional NF-κB site remains an exclusive property of subtype C. The acquired κB site is genetically distinct, binds the p50-p65 heterodimer, and strengthens the viral promoter at the levels of transcription initiation and elongation. The 4-κB viruses dominate the 3-κB “isogenic” viral strains in pairwise competition assays in T-cell lines, primary cells, and the ecotropic human immunodeficiency virus mouse model. The dominance of the 4-κB viral strains is also evident in the natural context when the subjects are coinfected with κB-variant viral strains. The mean plasma viral loads, but not CD4 counts, are significantly different in 4-κB infection suggesting that these newly emerging strains are probably more infectious. It is possible that higher plasma viral loads underlie selective transmission of the 4-κB viral strains. Several publications previously reported duplication or deletion of diverse transcription factor-binding sites in the viral promoter. Unlike previous reports, our study provides experimental evidence that the new viral strains gained a potential selective advantage as a consequence of the acquired transcription factor-binding sites and importantly that these strains have been expanding at the population level.

A LONGITUDINAL QUALITY-OF-LIFE STUDY OF HIV-INFECTED PERSONS IN SOUTH INDIA : THE CASE FOR COMPREHENSIVE CLINICAL CARE AND SUPPORT SERVICES

This study longitudinally assesses the quality of life (QOL) of HIV-infected individuals in a resource-limited setting prior to the extensive generic roll-out of highly active antiretroviral therapy. Data was collected on 136 individuals receiving clinical care at Y.R. Gaitonde Centre for AIDS Research and Education YRG CARE, a large community-based HIV tertiary care referral center in Chennai, South India. The QOL questionnaire was administered to participants at baseline, 6-months follow-up, and 12-month follow-up, and analysis of variance was used to assess for significant differences in mean QOL scores for each of these visits. Study findings showed that QOL scores significantly improved in all five domains of the questionnaire between participants baseline visit, second interview, and third interviews (p < 0.01). We conclude that a multidisciplinary approach to managing HIV infection can enhance patients QOL, independent of antiretroviral therapy.

GB virus infection: a silent anti-HIV panacea within?

The GB virus (GBV)/hepatitis G virus is a member of the Flaviviridae family and belongs to the hepatitis group of viruses transmitted parenterally, common among intravenous drug users. The strong association between GBV and HIV infection suggests that the two viruses may share similar epidemiological and transmission features. GBV infection is widely believed to prolong HIV disease progression as well as decreasing the HIV viral load and increasing the CD4(+) T-cell level. GBV-driven anti-E2 antibodies have been shown to inhibit HIV replication in vitro. Preliminary studies also suggest that GBV infection of peripheral blood mononuclear cells leads to increased production of beta-chemokines, which may explain the in vitro inhibitory effects and warrants further studies. With sufficient knowledge of resistance patterns studied in tropical south India, researchers are now keen to study the competitive interactions between GBV-induced chemokines and HIV ligands to bind CCR5.

Evaluation and diagnostic usefulness of domestic and imported enzyme-linked immunosorbent assays for detection of human immunodeficiency virus type 1 antibody in India

ABSTRACT Diagnosis of human immunodeficiency virus (HIV) infection is important for patient management and prevention of new infections. The number of test kits available for the detection of HIV antibodies is unprecedented. In order to identify appropriate test kits, we evaluated a variety of commercial kits manufactured abroad as well as in India. The plasma and serum specimens (n = 264) were collected from individuals attending the Voluntary Counseling and Testing Centre at the YRG Centre for AIDS and Education. The specimens were used to evaluate six commercially available HIV test kits: Enzaids HIV 1+2, HIV-CheX, Murex HIV-1.2.0, Genscreen HIV 1/2 version 2, Vironostika HIV Uni-Form II Ag/Ab, and CombAids RS Advantage. High sensitivities and specificities (≥99%) were observed for the Enzaids, Murex, Vironostika, and CombAids assays. HIV-CheX showed the highest number of false-positive and false-negative results. The Genscreen test also gave many false positives. The study indicated that the Enzaids, Murex, and Vironostika enzyme-linked immunosorbent assay kits and the CombAids RS Advantage rapid assay could be used to achieve acceptable results for the detection of HIV antibodies. A combination of two tests is recommended to optimize the efficiency of HIV antibody testing algorithms, especially when evaluation with an HIV Western blot confirmatory test is not possible.

Performance of Two Commercial Enzyme-Linked Immunosorbent Assay Kits Using Recombinant Glycoprotein G2 Antigen for Detection of Herpes Simplex Virus Type 2 Specific Antibodies

ABSTRACT For 93 stored serum samples tested by HerpeSelect2 and the Euroimmun enzyme-linked immunosorbent assay for detection of herpes simplex virus type 2-specific immunoglobulin G antibodies, the concordance of positive and negative results was 100%. Moreover, all the results that were equivocal by HerpeSelect2 (negative by Euroimmun) were confirmed as being negative by a Western blot assay.

Structural interventions in societal contexts

Publisher Summary HIV interventions that fundamentally alter the social context within which risk-taking behaviors occur are necessary for long-term, sustainable HIV prevention. There is certainly a need for structural interventions that address the needs of historically marginalized populations, which are often at great risk for HIV infection. Many current social-cognitive and cognitive-behavioral models that address HIV-related stigma may not be feasible in resource-limited settings, or operate using a highly individualized framework, which may be alien in more collective societies, such as in many parts of Africa, Asia, and Latin America. Though targeted HIV prevention programs are underway across the developing world, most of these efforts have historically been targeted at behavior change communication and condom distribution. A potential shortcoming of these modalities is that they can fail to address environmental factors that can organically lead to community-based social changes. Due to the sensitivity of openly discussing sex in public and the social stigma associated with HIV in many traditional societies, understanding the extent to which sexuality and sexual health are discussed in community venues can inform the design of HIV prevention interventions. Community-based health promotion relies on the communication of messages that helps in informing and empowering individuals to take control of their own health. Community mobilization, advocacy, and social change can serve as a localized intervention strategy to transform the ways in which individuals and communities respond to HIV and AIDS.

Accumulation of HIV-1 Drug Resistance Mutations After First-Line Immunological Failure to Evaluate the Options of Recycling NRTI Drugs in Second-Line Treatment: A Study from South India.

Lack of HIV-1 viral load monitoring in resource-limited settings leads to the development of HIV drug resistance mutations, although WHO recommends viral load testing for monitoring as this helps in preserving future treatment options and also avoid unnecessary switching to more expensive drugs. A total of 101 patients attaining first-line treatment failure (FTF) were followed until second-line treatment failure (STF) to study the rate of accumulation of thymidine analogue mutations (TAMs), their future drug options, and genetic evolution. The result shows that predominant nucleos(t)ide reverse transcriptase inhibitor (NRTI) mutations were M184V/I (87.3% in FTF and 79% in STF) followed by TAMs (53.4% in FTF and 54.5% in STF). The rate of accumulation of TAMs was higher for a patient with TAMI [0.015 TAM per person-month (TPPM)], TAMII (0.042 TPPM), and 1 (0.005 TPPM) or 2 TAMs (0.008 TPPM) compared with a patient with both TAMs and 3 or >3 TAMs. Future ART options show that >50% of the patients can be considered for choices to recycle NRTIs in the second-line, and third-line therapy. We conclude that the patients who initiated thymidine analogue-based first-line before 2010 can be very well opted for AZT- and TDF-based second-line regimen in the future.

Hiv-1 Drug Resistance Among Newly Hiv-1 Infected Individuals Attending Tertiary Referral Center in Chennai, India

CONTEXTnIn the era of free HAART, accessibility and availability of ARV has been dramatically increased in India. However, rates of treatment literacy and adherence appear to be sub-optimal. Therefore, it is essential to monitor the extent of primary drug resistance in such settings.nnnMATERIALS AND METHODSnBetween July and October 2006, 18 anti-retroviral-naοve individuals were identified as recent infected by the BED-Capture enzyme immunoassay in a VCTC clinic in Chennai. Specimens from these individuals were subjected to genotypic drug resistance testing. Phylogenetic trees were generated using MEGA for Windows version 4.0 using neighbor-joining method. The significant differences in polymorphic mutation frequencies between the study specimens and established subtype C-specific polymorphisms were examined using the Chi-square test.nnnRESULTSnAmino acid substitution (K103N and V106MV) at drug resistance positions occurred in two (11%) isolates, conferring high-level resistance to the non-nucleoside reverse-transcriptase inhibitors nevirapine (NVP), efavirenz (EFV), delavirdine (DLV) and notably extensive genetic variations were observed. K122E (94.4%) and K49R/KR (11.1%) polymorphisms identified in this study have not been previously described in established subtype-C specific polymorphisms. The rate of polymorphisms showed marked difference at the locations V60, D121, V35, and D123 (P < 0.0001). All the sequences showed maximum homology with Indian HIV-1 subtype C reference strain C.IN.95IN21068.nnnCONCLUSIONSnThe finding of resistance to NNRTIs is of public health importance. There is an urgent need to establish surveillance for primary drug resistance in large scale. Further studies are required to determine the phenotype impact of newer polymorphic mutations in relation to drug resistance and viral fitness.

Incidence of atazanavir- associated adverse drug reactions in second -line drugs treated south Indian HIV-1 infected patients

Background: Ritonavir-boosted atazanavir (ATV/r) is the preferred second-line protease inhibitor (PI) option for HIV patients in resource-limited settings; its pattern of adverse drug reactions (ADRs) has not been much reported from India; hence, in this study, we have analyzed the incidence of ATV/r-associated ADRs in Southern Indian HIV-1-infected patients. Methods: In this prospective study, 111 HIV patients treated with ATV/r were included with at least 2 years follow-up visits for the emergence of hyperbilirubinemia, hypertransaminasemia, and serum creatinine elevation. The causality assessment was done based on the WHO scale for the causality assessment of suspected ADR. Results: The incidence of severe hyperbilirubinemia, hypertransaminasemia, and creatinine elevation was 28.6, 0.76, and 1.62 cases/100 person years, respectively. 3TC/FTC + TDF (odds ratio [OR]: 6.07, confidence interval [CI]: 1.31–27.98, P = 0.015) nucleos (t) ide reverse transcriptase inhibitor backbone and male sex (OR: 18.64, CI: 2.13–162.93, P = 0.0082) were found to be significantly associated with hypertransaminasemia and creatinine elevation, respectively. The causality assessment of ADR was “possible” for all the participants. Kaplan–Meier analysis showed hyperbilirubinemia to emerge earlier (mean duration: 32.18 months, CI: 24.9–39.4 months) followed by hypertransaminasemia and creatinine elevation. Hyperbilirubinemia is an expected side effect associated with ATV/r which is benign, transient, and does not predispose to hypertransaminasemia. Conclusion: Our study results show that patients starting ATV/r should be counseled for a good adherence in spite of the emergence of hyperbilirubinemia which generally reverts to normal range.

Common protozoans as an uncommon cause of respiratory ailments in HIV-associated immunodeficiency.

Opportunistic infections (OIs) are the leading cause of mortality and morbidity among HIV-positive subjects. The breadth of reports of the rare occurrence of OIs in HIV/AIDS has been increasing over the years and more recent studies have outlined the changing trends in the emergence of newer pathogens. Recent reports of the association of certain protozoans that normally do not infect sites other than their normal sites of localization have generated huge interest among scientists. The complete depression of the immune system, followed by the onset of OIs, especially due to protozoans, i.e. toxoplasmosis, isosporiasis, leishmaniasis, cyclosporosis, microsporidiosis and cryptosporidiosis, is not uncommon in AIDS. The immunologic and pathologic basis behind the susceptibility of immunodepressed individuals to these non-site-specific parasites is likely to have a huge impact on HIV disease progression. Certain possible shortcomings in the immunologic armory of immunodeficient subjects, their failure to contain the establishment of these uncommon agents in the human host and their significance in HIV disease progression are discussed.