Jayaseelan Boobalan

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.

Performance of point-of-care Xpert HIV-1 plasma viral load assay at a tertiary HIV care centre in Southern India

Background. Sustainable suppression of HIV replication forms the basis of anti‐retroviral therapy (ART) medication. Thus, reliable quantification of HIV viral load has become an essential factor to monitor the effectiveness of the ART. Longer turnaround‐time (TAT), batch testing and technical skills are major drawbacks of standard real‐time PCR assays. Methods. The performance of the point‐of‐care Xpert HIV‐1 viral load assay was evaluated against the Abbott RealTime PCR m2000rt system. A total of 96 plasma specimens ranging from 2.5 log10 copies ml‐1 to 4.99 log10 copies ml‐1 and proficiency testing panel specimens were used. Precision and accuracy were checked using the Pearson correlation co‐efficient test and Bland‐Altman analysis. Results. Compared to the Abbott RealTime PCR, the Xpert HIV‐1 viral load assay showed a good correlation (Pearson r=0.81; P<0.0001) with a mean difference of 0.27 log10 copies ml‐1 (95 % CI, −0.41 to 0.96 log10 copies ml‐1; sd, 0.35 log10 copies ml‐1). Conclusion. Reliable and ease of testing individual specimens could make the Xpert HIV‐1 viral load assay an efficient alternative method for ART monitoring in clinical management of HIV disease in resource‐limited settings. The rapid test results (less than 2 h) could help in making an immediate clinical decision, which further strengthens patient care.

Anti-HIV microRNA expression in a novel Indian cohort

HIV-1 replication inside host cells is known to be regulated by various host factors. Host miRNAs, by virtue of its normal functioning, also regulate HIV-1 RNA expression by either directly targeting virus mRNAs or indirectly by regulating host proteins that HIV-1 uses for own replication. Therefore, it is highly possible that with differential miRNA expression, rate of disease progression will vary in HIV-1 infected individuals. In this study we have compared expression of a panel of 13 reported anti-HIV miRNAs in human PBMCs from long term non progressors (LTNPs), regular progressors and rapid progressors. We found that LTNPs have substantial lower expression of miR-382-5p that positively correlates with viral loads. Combinatorial regulation is highly probable in dictating differential disease progression as average expression of miR-382-5p and miR-155-5p can substantially distinguish LTNP individuals from regular progressors.

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.

Occult HBV infection in HIV-infected adults and evaluation of pooled NAT for HBV

The study aimed to determine the prevalence of occult hepatitis B virus infection among HIV‐infected persons and to evaluate the use of a pooling strategy to detect occult HBV infection in the setting of HIV infection. Five hundred and two HIV‐positive individuals were tested for HBV, occult HBV and hepatitis C and D with serologic and nucleic acid testing (NAT). We also evaluated a pooled NAT strategy for screening occult HBV infection among the HIV‐positive individuals. The prevalence of HBV infection among HIV‐positive individuals was 32 (6.4%), and occult HBV prevalence was 10%. The pooling HBV NAT had a sensitivity of 66.7% and specificity of 100%, compared to HBV DNA NAT of individual samples. In conclusion, this study found a high prevalence of occult HBV infection among our HIV‐infected population. We also demonstrated that pooled HBV NAT is highly specific, moderately sensitive and cost‐effective. As conventional HBV viral load assays are expensive in resource‐limited settings such as India, pooled HBV DNA NAT might be a good way for detecting occult HBV infection and will reduce HBV‐associated complications.

Cost-effective HIV-1 virological monitoring in resource-limited settings using a modified commercially available qPCR RNA assay

Virological monitoring through plasma viral load (PVL) quantification is essential for clinical management of HIV patients undergoing antiretroviral treatment (ART), and for detecting treatment failure. Quantitative PCR (qPCR)-based tests are the gold standard for measuring PVL. Largely because of their high cost, however, implementation of these tests in low- and middle-income countries fails to cover the testing demand. In this study, we aimed at reducing the running cost of the commercially available Abbott RealTime™ HIV-1 assay by minimizing the reagent consumption. To this end, a modified version of the assay was obtained by reducing the assays reagents volume to about a half, and validated using a panel of 104 plasma samples. Compared to the standard version, the modified Abbott assay allowed for a 50% reduction in running costs. At the same time, it showed a 100% concordance in identifying samples with detectable viral load, strong correlation (Pearsons r=0.983, P<0.0001), and a high agreement between PVL values (mean percent difference between PVL values±standard deviation=0.76±3.18%). In detecting viral failure (PVL>1000copiesmL-1), the modified assay showed a sensitivity of 94.6%, a specificity of 93.8%, and a negative and positive predictive values of 93.8% and 94.6%, respectively. The modified assay therefore reliably quantifies PVL, predicts viral failure, and allows for a ca. 50% reduction in the assays running costs. It may thus be implemented as an ART monitoring tool in resource-limited settings and for research purposes.

HIV, HBV and HCV prevalence among high risk populations in South India

Author(s): Dinesha, Thongadi Ramesh; Boobalan, Jayaseelan; Sivamalar, Sathasivam; Solomon, Sunil S; Poongulali, Selvamuthu; Pradeep, Ambrose; Murugavel, Kailapuri G; Balakrishnan, Pachamuthu; Smith, Davey M; Saravanan, Shanmugam