Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection

Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis.     

New bioanalytical microemulsion Electrokinetic chromatography method for the simultaneous determination of Trifluridine with its metabolites and Tipiracil in rat plasma: Application to pharmacokinetic studies

A Microemulsion Electrokinetic Chromatography method coupled with diode array detector (MEEKC-DAD) was developed for the first time and found to be efficient, sensitive, and selective for the simultaneous analysis of Trifluridine (FTD), and its metabolites 5-(trifluoromethyl) uracil (FTY) and 5-carboxy-2′-deoxyuridine (5CDU), and Tipiracil (TIP) in rat plasma. Sample pre-treatment involved a simple protein precipitation from plasma using acetonitrile. The separation was achieved using a fused silica capillary (65 cm total length, 55 cm effective length and 50 µm i.d.) and a microemulsion solution consisted of 1.66% sodium dodecyl sulfate (SDS), 0.91% heptane, 6.61% 1-butanol, and 90.72% borate buffer (20 mM, pH 9.5). Electrophoretic separation was carried out at 20 °C and 20 kV. The samples were injected for 40 s at 20 mbar and detected simultaneously at 205 nm. The electrophoretic parameters indicated that the developed MEEKC-DAD method permitted complete resolution of the analytes within 13 min. The developed method was fully validated according to the FDA guidelines for bioanalytical method validation. The method was linear in the range 200–4000 ng/ml for FTD, FTY, 5CDU, and 100–1000 ng/ml for TIP. The intra/inter-day accuracy and precisions were ≤4% for all drugs. Extraction recovery and stability were also assessed and were within acceptable range. After being validated, the method was applied for the determination of the studied drugs in plasma samples collected from rats injected intraperitoneally with a combination of FTD and TIP. The results obtained were used to study the pharmacokinetics of FTD with its metabolite and TIP in rat plasma.     

Attitudes toward medication-assisted treatment among fishermen in Kuantan,Malaysia, who inject drugs

Fishermen who inject drugs represent an understudied group at high risk for HIV in Malaysia. This study describes fishing, drug use, and attitudes toward medication-assisted treatment (MAT) for opioid use disorders. Thirty-four male ethnic Malay fishermen completed semistructured interviews analyzed by content analysis. Analysis revealed four themes surrounding opioids, which they called ubat (“medicine”): (a) the fishing lifestyle facilitating substance use, (b) previous unsuccessful attempts to quit, (c) categorizing substances as haram or halal, and (d) attitudes toward MAT. Fishermen's environment permits substance use, including injecting drugs on boats. Fishermen expressed more positive attitudes toward methadone and negative attitudes toward buprenorphine.     

Case Series of Buprenorphine Injectors in Kuala Lumpur,Malaysia

Diversion of buprenorphine has been described in settings where it is legally prescribed and has become an increasing concern in Malaysia; it resulted in banning of buprenorphine in Singapore where unsubstantiated case reports suggested that buprenorphine injection was associated with particularly poor outcomes. We therefore conducted a case series of qualitative interviews with buprenorphine injectors in Kuala Lumpur, Malaysia to examine further the issues surrounding buprenorphine injection as well as the abuse of midazolam in combination with buprenorphine. Interviews with 19 men do not suggest significant adverse health consequences from buprenorphine injection alone and injectors have adapted diverted buprenorphine as a treatment modality. A subset of these injectors, however, combined buprenorphine and midazolam for euphoric effects with resultant symptoms of a possible pharmacological interaction. Prospective cohort studies, rather than hospital-derived samples, are needed to better understand the safety of buprenorphine injection.     

Continuous crossover(s) events of HIV-1 CRF01_AE and B subtype strains in Malaysia: evidence of rapid and extensive HIV-1 evolution in the region

The Asian HIV epidemic appears to be complex, characterized by the prevalence of multiple subtypes and circulating recombinant forms with gradual replacement of pure HIV-1 subtypes in several geographical regions. The main objectives of the present study are to identify and analyse the full-length viral genomes of three unique recombinant forms (URFs); the HIV-1 isolates 07MYKLD47, 07MYKLD48 and 07MYKLD49 from Malaysia. Long-range polymerase chain reaction (PCR) amplification of seven overlapping reading frames was used to derive near full-length HIV-1 genomes. Detailed phylogenetic and bootscanning analyses were performed to determine phylogenetic associations and subtypic assignments. We further confirmed the mosaic composition of these CRF01_AE/B inter-subtype recombinant forms, which are composed of B-subtype fragment(s) in the backbone of CRF01_AE. Both 07MYKLD47 and 07MYKLD48 have an insertion of B subtype (880 bp and 532 bp) in the gag-pol and gp41-env gene regions, respectively. Whereas the isolate 07MYKLD49 has three B-subtype fragments inserted in different gene region along the genome; one each in the gag-pol (1862 bp) and pol-vif (1935 bp) regions, and a short B-subtype insertion (541 bp) in the 5' LTR-gag region. This highlights the public health relevance of newly emerging second generation HIV-1 recombinant forms and their dispersal, along with their rapid and continuous evolution in the region.