Analyses of HIV-1 integrase sequences prior to South African national HIV-treatment program and available of integrase inhibitors in Cape Town, South Africa

HIV-Integrase (IN) has proven to be a viable target for highly specific HIV-1 therapy. We aimed to characterize the HIV-1 IN gene in a South African context and identify resistance-associated mutations (RAMs) against available first and second generation Integrase strand-transfer inhibitors (InSTIs). We performed genetic analyses on 91 treatment-naïve HIV-1 infected patients, as well as 314 treatmentnaive South African HIV-1 IN-sequences, downloaded from Los Alamos HIV Sequence Database. Genotypic analyses revealed the absence of major RAMs in the cohort collected before the broad availability of combination antiretroviral therapy (cART) and INSTI in South Africa, however, occurred at a rate of 2.85% (9/314) in database derived sequences. RAMs were present at IN-positions 66, 92, 143, 147 and 148, all of which may confer resistance to Raltegravir (RAL) and Elvitegravir (EVG), but are unlikely to affect second-generation Dolutegravir (DTG), except mutations in the Q148 pathway. Furthermore, protein modeling showed, naturally occurring polymorphisms impact the stability of the intasome-complex and therefore may contribute to an overall potency against InSTIs. Our data suggest the prevalence of InSTI RAMs, against InSTIs, is low in South Africa, but natural polymorphisms and subtype-specific differences may influence the effect of individual treatment regimens

Degradation of haloaromatic compounds

An ever increasing number of halogenated organic compounds has been produced by industry in the last few decades. These compounds are employed as biocides, for synthetic polymers, as solvents, and as synthetic intermediates. Production figures are often incomplete, and total production has frequently to be extrapolated from estimates for individual countries. Compounds of this type as a rule are highly persistent against biodegradation and belong, as "recalcitrant" chemicals, to the class of so-called xenobiotics. This term is used to characterise chemical substances which have no or limited structural analogy to natural compounds for which degradation pathways have evolved over billions of years. Xenobiotics frequently have some common features. e.g. high octanol/water partitioning coefficients and low water solubility which makes for a high accumulation ratio in the biosphere (bioaccumulation potential). Recalcitrant compounds therefore are found accumulated in mammals, especially in fat tissue, animal milk supplies and also in human milk. Highly sophisticated analytical techniques have been developed for the detection of organochlorines at the trace and ultratrace level