Gentamicin/azithromycin and gemifloxacin/azithromycin were highly effective for treatment of urogenital gonorrhea. Gastrointestinal adverse events may limit routine use. These non-cephalosporin-based regimens may be useful alternative options for patients who cannot be treated with cephalosporin antimicrobials. Additional treatment options for gonorrhea are needed. Clinical Trials Registration. NCT00926796.

Infidelity of DNA synthesis by human immunodeficiency virus, type 1 reverse transcriptase (HIV-1 RT) is a presumptive determinant of HIV-1 hypervariability and is incompletely understood at the mechanistic and structural levels. Amino acid substitution at only three residues, including Asp-76 (Kim, B., Hathaway, T. R., and Loeb, L. A. (1996) Biochemistry 37, 5831-5839), is known to increase fidelity. We report here that substitution at Arg-78 can also increase accuracy. Mutant R78A RT showed reduced primer extension in misincorporation assays lacking a complementary dNTP and exhibited a 9-fold decrease in mutation frequency in the M13mp2 lacZ forward mutation assay. Previous structural studies indicate that Arg-78 and Asp-76 lie in a region that interacts with template nucleotides. Interestingly, R78A RT exhibited 6-to 8-fold decreases in binding affinity (K d ) for RNA and DNA templates relative to wild type RT. In contrast, D76V RT, which also increases fidelity (Kim et al., 1996), showed a 6-to 7-fold increased affinity. The processivity of R78A RT on both RNA and DNA templates was substantially reduced relative to wild type RT, whereas the processivity of D76V RT was increased. We discuss relationships of fidelity, template binding, and processivity in these and other HIV RT mutants.Genomic hypervariability is a defense device that allows human immunodeficiency virus, type 1 (HIV-1) 1 to escape from selection pressure such as that imposed by the host immune system or drug therapies. Hypervariation of HIV-1 genomes can be achieved by at least three unique viral replication processes. First, mutations can be synthesized by the virally encoded DNA polymerase, HIV-1 reverse transcriptase (RT) (1, 2). HIV-1 RT is the most error prone of all known DNA polymerases (3-7). Second, mutations produced by HIV-1 RT can be amplified by recombination, which has been observed in virions containing heterogeneous diploid genomes (8). It has been suggested that the occurrence of homologous recombination during viral replication is related to the processivity and strand transfer activity of HIV-1 RT (9, 10). Finally, constant, massive replication amplifies the complexity of the viral population (11).The structural basis of HIV-1 RT infidelity remains to be fully elucidated. Lack of a 3Ј-5Ј proofreading exonuclease activity is a presumptive factor (4), but it cannot be the only determinant, because other retroviral RTs that lack a proofreading exonuclease, such as murine leukemia virus RT and AMV RT, have 10-to 18-fold higher fidelity (3). Our knowledge of the structure-function relationships governing the accuracy of other DNA polymerases rests heavily on the analysis of mutants (12, 13); the classic mutants of Escherichia coli DNA polymerase I are important examples (14). Currently available mutants of HIV-1 RT are mostly drug-resistant variants isolated from patients and cell culture systems. Interestingly, it has been reported that drug resistance mutations at Met-184 (M184V, M184I) and Glu-89 (E89G) confer increased fidelit...

Increasing access to human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) is a high priority for the Ending the HIV Epidemic Initiative. Expanding access to PrEP and PEP through a variety of health care settings, including community pharmacies, may increase access in communities most in need. California is the first state to allow community pharmacists to furnish PrEP and PEP directly to consumers. Our objective was to assess attitudes among key stakeholders about a California policy to allow community pharmacists to furnish HIV PrEP and PEP. Methods: We conducted a qualitative case study with key pharmacy stakeholders. Semistructured phone interviews were audio-recorded and transcribed verbatim. We generated analytical memos for each interview and working with these analytical memos, we conducted a constant comparison across cases to identify commonalities and differences. Results: We launched the study in October 2018 and interviewed pharmacists (n ¼ 7) working in a variety of settings, including retail-, clinic-, and community-based pharmacies. We also interviewed medical providers (n ¼ 2) working in high-volume PrEP clinics and sought input from representatives of large retail chain pharmacies (n ¼ 2). Overall, pharmacists and medical provider informants shared similar opinions about the central benefits as well as the key challenges related to pharmacist-delivered PrEP and PEP services. Benefits included: community pharmacists are widely accessible, PrEP and PEP protocols are similar to other preventative medications, policy may lead to efficiencies in the health care workforce, and community pharmacists are authorities on medication adherence. Challenges included: implementation issues may limit pharmacist involvement, and missed opportunities to diagnose and treat other health conditions. Conclusion: This study characterizes the types of benefits and challenges that can be expected when PrEP and PEP prescribing privileges are extended to community pharmacists. This information may be useful to policymakers and other stakeholders considering legislation to permit direct prescription of PrEP and PEP by pharmacists.

BackgroundResearch on gay and other men who have sex with men's (G/MSM) preferences for sexual healthcare services focuses largely on HIV testing and to some extent on sexually transmitted infections (STI). This research illustrates the frequency and location of where G/MSM interface with the healthcare system, but it does not speak to why men seek care in those locations. As HIV and STI prevention strategies evolve, evidence about G/MSM's motivations and decision-making can inform future plans to optimize models of HIV/STI prevention and primary care.MethodsWe conducted a phenomenological study of gay men's sexual health seeking experiences, which included 32 in-depth interviews with gay and bisexual men. Interviews were transcribed verbatim and entered into Atlas.ti. We conducted a Framework Analysis.FindingsWe identified a continuum of sexual healthcare seeking practices and their associated drivers. Men differed in their preferences for separating sexual healthcare from other forms of healthcare (“fragmentation”) versus combining all care into one location (“consolidation”). Fragmentation drivers included: fear of being monitored by insurance companies, a desire to seek non-judgmental providers with expertise in sexual health, a desire for rapid HIV testing, perceiving sexual health services as more convenient than primary care services, and a lack of healthcare coverage. Consolidation drivers included: a comfortable and trusting relationship with a provider, a desire for one provider to oversee overall health and those with access to public or private health insurance.ConclusionsMen in this study were likely to separate sexual healthcare from primary care. Based on this finding, we recommend placing new combination HIV/STI prevention interventions within sexual health clinics. Furthermore, given the evolution of the financing and delivery of healthcare services and in HIV prevention, policymakers and clinicians should consider including more primary care services within sexual healthcare settings.