Combination of G2-S16 dendrimer/dapivirine antiretroviral as a new HIV-1 microbicide

Aim: To research the synergistic activity of G2-S16 dendrimer and dapivirine (DPV) antiretroviral as microbicide candidate to prevent HIV-1 infection. Materials & methods: We assess the toxicity of DPV on cell lines by MTT assay, the anti-HIV-1 activity of G2-S16 and DPV alone or combined at several fixed ratios. Finally, their ability to inhibit the bacterial growth in vitro was assayed. The analysis of combinatorial effects and the effective concentrations were performed with CalcuSyn software. Conclusion: Our results represent the first proof-of-concept study of G2-S16/DPV combination to develop a safe microbicide.

Imaginings of Empowerment and the Biomedical Production of Bodies

In this paper, I will explore the development of vaginal microbicides (female-initiated HIV prevention methods designed as gels, films, sponges and rings women can insert vaginally before having sex to protect themselves against HIV infection) as a women’s health intervention that entangles feminist ideals of empowerment with biomedical enterprise. The field of vaginal microbicide development pays heed to both the specific biological vulnerabilities of ‘the female body’ that are understood to make women more susceptible to HIV infection as well as the social gendered power relations that leave women at a higher risk of HIV within the power dynamics of their sexual relationships. I am particularly interested in the ambiguity that emerges between the effects of a biomedical search for facticity through clinical trial testing and advocacy promises of empowerment, which I will explore through analysing the clinical trials of Nonoxynol-9 microbicide candidates in the early 1990s – a microbicide candidate that was continuously linked to vaginal ulceration and consequently a potential increase in receptivity to HIV. Through an interrogation of clinical trial reports, advocacy documents and a social science study in which the women trial participants articulated Nonoxynol-9 as their “protector”, I argue that the story of Nonoxynol-9 shows an intrinsic ambiguity between the field’s feminist promise of empowerment and the effects of the biomedical search for an effective microbicide candidate. Drawing on the work of Karen Barad, I argue that agential realism is able to provide a robust analytical framework to interrogate the political and ethical effects of this ambiguity that the field’s own discourse of empowerment does not provide. Key words: HIV, vaginal microbicides, agential realism, global health, new materialism

Sensitivity of transmitted and founder human immunodeficiency virus type 1 envelopes to carbohydrate-binding agents griffithsin, cyanovirin-N and Galanthus nivalis agglutinin

Human immunodeficiency virus type 1 (HIV-1) transmission often results from infection by a single transmitted/founder (T/F) virus. Here, we investigated the sensitivity of T/F HIV-1 envelope glycoproteins (Envs) to microbicide candidate carbohydrate-binding agents (CBAs) griffithsin (GRFT), cyanovirin-N (CV-N) and Galanthus nivalis agglutinin (GNA), showing that T/F Envs demonstrated different sensitivity to CBAs, with IC50 values ranging from 0.006 ± 0.0003 to >10 nM for GRFT, from 0.6 ± 0.2 to 28.9 ± 2.9 nM for CV-N and from 1.3 ± 0.2 to >500 nM for GNA. We further revealed that deglycosylation at position 295 or 448 decreased the sensitivity of T/F Env to GRFT, and at 339 to both CV-N and GNA. Mutation of all the three glcyans rendered a CBA-sensitive T/F Env largely resistant to GRFT, indicating that the sensitivity of T/F Env to GRFT is mainly determined by glycans at 295, 339 and 448. Our study identified specific T/F Env residues associated with CBA sensitivity.