Limited Neutralizing Antibody Specificities Drive Neutralization Escape in Early HIV-1 Subtype C Infection

We previously showed that HIV-1 subtype C viruses elicit potent but highly type-specific neutralizing antibodies (nAb) within the first year of infection. In order to determine the specificity and evolution of these autologous nAbs, we examined neutralization escape in four individuals whose responses against the earliest envelope differed in magnitude and potency. Neutralization escape occurred in all participants, with later viruses showing decreased sensitivity to contemporaneous sera, although they retained sensitivity to new nAb responses. Early nAb responses were very restricted, occurring sequentially and targeting only two regions of the envelope. In V1V2, limited amino acid changes often involving indels or glycans, mediated partial or complete escape, with nAbs targeting the V1V2 region directly in 2 cases. The alpha-2 helix of C3 was also a nAb target, with neutralization escape associated with changes to positively charged residues. In one individual, relatively high titers of anti-C3 nAbs were required to drive genetic escape, taking up to 7 weeks for the resistant variant to predominate. Thereafter titers waned but were still measurable. Development of this single anti-C3 nAb specificity was associated with a 7-fold drop in HIV-1 viral load and a 4-fold rebound as the escape mutation emerged. Overall, our data suggest the development of a very limited number of neutralizing antibody specificities during the early stages of HIV-1 subtype C infection, with temporal fluctuations in specificities as escape occurs. While the mechanism of neutralization escape appears to vary between individuals, the involvement of limited regions suggests there might be common vulnerabilities in the HIV-1 subtype C transmitted envelope

Prevalence of methicillin resistance and macrolide–lincosamide–streptogramin B resistance in Staphylococcus haemolyticus among clinical strains at a tertiary-care hospital in Thailand

Staphylococcus spp. is a major cause of nosocomial infection and sepsis. However, increasing drug resistance is becoming a challenge to microbiologists. The purpose of this study was to identify and determine antimicrobial resistance phenotypes and drug resistance genes of clinical coagulase-negative staphylococci (CoNS) isolates at Mae Sot Hospital in Tak province, Thailand. A total of 229 CoNS isolates were collected from clinical specimens during two periods in 2014 and in 2015. Staphylococcus haemolyticus was the most prevalent species (37.55%), followed by S. epidermidis (21.83%), S. saprophyticus (11.79%) and S. hominis (11.35%) respectively. The remaining 17.48% of the organisms comprised S. capitis, S. arlettae, S. cohnii, S. equorum, S. xylosus, S. warneri, S. sciuri, S. pettenkoferi, S. kloosii and S. lugdunensis. Methicillin-resistant CoNS (MRCoNS), containing the mecA gene, were detected in 145 of 229 isolates, mostly found in S. haemolyticus and S. epidermidis. In addition, the differentiation of their macrolide–lincosamide–streptogramin B (MLSB) resistance phenotypes was determined by the D-test and corresponding resistance genes. Among 125 erythromycin-resistant CoNS, the prevalence of constitutive type of MLSB, inducible clindamycin resistance and macrolide–streptogramin B resistance phenotypes were 72, 13.60 and 14.40% respectively. These phenotypes were expressed in 80% of MRCoNS strains. In addition, the ermC gene (79.20%) was found to be more prevalent than the ermA gene (22.40%), especially among MRCoNS. These results indicate that CoNS may play an important role in spreading of drug resistance genes. More attention to these organisms in surveillance and monitoring programs is needed