Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens.

Human immunodeficiency virus type 2 (HIV-2) is intrinsically resistant to non-nucleoside reverse transcriptase inhibitors and exhibits reduced susceptibility to several of the protease inhibitors used for antiretroviral therapy of HIV-1. Thus, there is a pressing need to identify new classes of antiretroviral agents that are active against HIV-2. Although recent data suggest that the integrase strand transfer inhibitors raltegravir and elvitegravir may be beneficial, mutations that are known to confer resistance to these drugs in HIV-1 have been reported in HIV-2 sequences from patients receiving raltegravir-containing regimens. To examine the phenotypic effects of mutations that emerge during raltegravir treatment, we constructed a panel of HIV-2 integrase variants using site-directed mutagenesis and measured the susceptibilities of the mutant strains to raltegravir and elvitegravir in culture. The effects of single and multiple amino acid changes on HIV-2 replication capacity were also evaluated. Our results demonstrate that secondary replacements in the integrase protein play key roles in the development of integrase inhibitor resistance in HIV-2. Collectively, our data define three major mutational pathways to high-level raltegravir and elvitegravir resistance: i) E92Q+Y143C or T97A+Y143C, ii) G140S+Q148R, and iii) E92Q+N155H. These findings preclude the sequential use of raltegravir and elvitegravir (or vice versa) for HIV-2 treatment and provide important information for clinical monitoring of integrase inhibitor resistance in HIV-2-infected individuals.

Aquatic-Aerobic Exercise as a Means of Stress Reduction during Pregnancy.

The goals of this research were to explore the current literature regarding associations between psychological stress and adverse fetal outcome, associations between aerobic exercise and psychological stress reduction, and associations between aerobic exercise and fetal outcome. The published studies that were located provide evidence of the following: 1) Stress reactivity increases physiologically during pregnancy, 2) pregnant women may experience additional stressors that are usually not experienced in a nonpregnant state, 3) psychological stress in pregnancy is associated with adverse fetal outcome, 4) exercise can be a method of stress reduction, 5) exercise in pregnancy is not associated with adverse fetal outcome, and 6) exercise in pregnancy may provide benefit to the fetus. Data were analyzed from an original study and associations were reported between psychological stress-management activities and participation in aquatic aerobic exercise classes. No reports were available investigating an exercise-induced reduction in psychological stress with fetal outcome.