Chlamydia trachomatis is the most common bacterial agent of sexually transmitted infections worldwide and a common co-infection in AIDS patients. Chlamydial genital tract infections are often asymptomatic; therefore many infections go untreated and result in complications like chronic inflammation, ectopic pregnancy, and pelvic inflammatory disease. Chlamydia share a unique developmental cycle and under stress, can enter a state known as persistence, in which the bacteria are noninfectious but still viable. Removal of the stressor allows the chlamydiae to re-enter and complete the developmental cycle. Exposure to low-dose quinolones can cause the chlamydiae to enter persistence and halt the developmental cycle. Notably, 1 in 20 people living with HIV/AIDS also suffers from chlamydial infections. Since the anti-HIV drug Elvitegravir (EVG) is a quinolone derivative, we hypothesized that EVG exposure would inhibit chlamydial development. To ascertain whether EVG affects chlamydial development, HeLa cells were infected with C. trachomatis or C. muridarum and then either mock treated or treated with EVG. The percent infectivity and production of infectious progeny were determined by immunofluorescence assay and chlamydial titer assay, respectively. Transmission electron microscopy (TEM) was used to examine chlamydial morphology and determine whether EVG caused Chlamydia to become persistent. Though percent infectivity and chlamydial morphology were similar between treated and untreated Chlamydia-infected cells, the production of infectious progeny was significantly decreased in EVG-exposed Chlamydia-infected cells. These data indicate that EVG is not a persistence-inducer, but does inhibit chlamydial development in vitro. In other studies, we tested chlamydial polymorphic membrane protein (PMP) expression in chlamydia/HSV co-infected cells by immunofluorescence staining. Since penicillin-induced persistence decreases the expression of some chlamydial PMPs, we hypothesized that expression of PMP-A and PMP-B would be decreased by HSV-induced persistence. The results indicated that there was no significant difference in expression of PMP-A or PMP-B in co-infected versus C. trachomatis singly-infected cells. These data suggest that PMP expression is not a good indicator of chlamydial persistence when induced by HSV.

As HIV is now primarily a chronic condition, treatment is given life-long with changes as necessitated by alterations in tolerability and efficacy. Thus, personalized medicine may be useful in the prevention of unnecessary drug exposure and avoidable side effects. Three of the four currently available HIV integrase strand transfer inhibitors (INSTIs), raltegravir, elvitegravir, and dolutegravir, are widely utilized antiretrovirals in the USA and exhibit variations in outcomes among subjects. To interrogate differences among subjects receiving these drugs, we investigated the association of several single nucleotide polymorphisms (SNPs) with drug exposure, clinical outcomes, and subject-reported adverse events. HIV+ adults (≥18 years old) receiving an INSTI regimen were recruited (n=88). Subject genotypes were evaluated using an iPLEX PGx Panel. Genetic variations within our population, underwent multiple regression with covariates [age, sex, BMI, regimen duration, and baseline variables (as required) along with specific regimen in the comprehensive group] to detect significant (p=0.028) between abnormal dream occurrence and specific INSTI regimen with the raltegravir grouping presenting a higher frequency. This exploratory study also discovered several SNP-outcome associations when using INSTIs. Although these SNPs were found to have a role in predicting segments of adverse effect profiles, the clinical significance of these findings remains to be determined. Larger studies will be needed to confirm these exploratory findings with functional studies to understand pathogeneses. In conclusion, the associations found in this study strengthen the need for further assessment, within the HIV+ population, of factors contributing to unfavorable subject outcomes.

BACKGROUND: Numerous methods have been devised to combat human immunodeficiency virus (HIV) replication and disease progression. Composed of an integrase strand transfer inhibitor, a pharmacoenhancer, and two reverse transcriptase inhibitors, Stribild is a relatively new combination HIV drug formulated for once-a-day dosing. METHODS: Relevant information, original research articles and reviews, were gathered primarily through the use of the PubMed database. The search was conducted without date restrictions in order to collect both historical and recent information concerning HIV, individual drugs, and combinations for a thorough overview. RESULTS: Stribild, when taken with food, provides therapeutic drug concentrations as seen through comparison with the respective individual or boosted individual drugs. Stribild non-inferiority has been shown when compared to other HIV drug combinations, ritonavir-boosted atazanavir or efavirenz each with a tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) backbone. The co-formulation also retained high viral suppression in patients switching from other regimens, such as efavirenz/TDF/FTC, raltegravir/TDF/FTC, or various ritonavir-boosted protease inhibitors with TDF/FTC. The elvitegravir and cobicistat combination was unaffected by moderate hepatic impairment; however, hepatic and renal function along with changes in bone mineral density should be monitored closely. Stribild presented with relatively few side effect occurrences, but drug interactions may pose a larger problem for continuous therapy. CONCLUSIONS: Stribild provides viral suppression, comparable to other combination HIV drugs through review of non-inferiority and regimen simplification studies, with minimal adverse effects. Although the breadth of Stribild effectiveness has begun to unfold, studies are lacking in older patients as well as adolescents.