Metronidazole treatment failure and persistent bacterial vaginosis: Implications for HIV susceptibility | Image Credit: © fizkes - © fizkes - stock.adobe.com.
Metronidazole (MDZ) treatment failure is associated with increased activated T- and dendritic-cell subsets expression, potentially causing a rise in HIV susceptibility, according to a recent study published in Microorganisms.
- The study highlights that metronidazole (MDZ) treatment failure in bacterial vaginosis (BV) is linked to increased expression of activated T- and dendritic-cell subsets. This failure may contribute to heightened susceptibility to HIV, suggesting the need for alternative treatment strategies.
- Although MDZ treatment reduces bacterial abundance associated with BV, the re-colonization with Lactobacillus species is often slow. BV recurrence rates remain high at up to 60%, emphasizing the challenges in achieving a stable and healthy vaginal microbiome after treatment.
- BV is associated with increased genital inflammation, which can lead to adverse sexual and reproductive outcomes, including a higher risk of sexually transmitted infections (STIs) such as HIV. The study underscores the importance of understanding and addressing the mucosal immune environment in the context of BV resolution.
- The investigation employed an ex vivo study design using endocervical cytobrushes from women enrolled in the CAPRISA 083. This design aimed to explore the relationship between BV resolution and mucosal immune response.
- Given the observed frequent treatment failure and persistent BV, the study suggests exploring alternative strategies to improve Lactobacillus representation. These include pre- and pro-biotics, vaginal microbiome transplantation, and the use of phage endolysins.
Bacterial vaginosis (BV), a polymicrobial condition in the female genital tract (FGT), is often treated using topical or oral MDZ. Treatment is associated with decreased bacterial abundance of BV-associated bacteria. However, re-colonization with Lactobacillus species is often slow, with BV recurrence rates up to 60%.
BV increases genital inflammation levels, which leads to adverse sexual and reproductive outcomes including sexually transmitted infections (STIs) such as HIV. While study authors state, “studies have demonstrated that vaginal microbiota modulates cytokine and cellular immune response signatures of HIV risk,” there is little data on whether MDZ treatment leads to mucosal immune environment changes.
To determine the relationship between BV resolution and the mucosal immune response, investigators conducted an ex vivo study using endocervical cytobrushes from 32 women diagnosed with STI or BV-intermediate or -positive. Participants were enrolled in the CAPRISA 083, which focused on enhancing management packages for STI care.
Exclusion criteria included pregnancy, living with HIV, and receiving antibiotic treatment within the previous 7 days. Women were consulted for follow-up if they were diagnosed with Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalisor, candidiasis, or had a Nugent score of 4 or higher.
Vaginal swabs with a Nugent score below 4 were normal, those with a score of 4 to 6 intermediate, and those with a score of 7 or greater Nugent-BV. BV was defined as a Nugent score of 4 or higher, but women with a score of 4 or higher at baseline and 6 weeks posttreatment but not 12 weeks posttreatment were identified as BV cleared.
Women with a Nugent score of 4 or higher at baseline and all following visits were identified as BV persistence. Those with a Nugent score below 4 at 6 weeks posttreatment but above 5 at 12 weeks posttreatment were identified as BV recurrence.
Across 32 participants, there were 16S rRNA gene sequences, cytokine, and cellular data. Patients were aged a median 24 years, with over 2/3 using condoms during the study. However, only 6% of these women consistently used condoms, and only 47% of all participants used any contraception.
Evidence of genital inflammation was reported in 28% of participants at baseline. At 6 weeks, inflammation was reported in 22%, and at 12 weeks in 19%. Nugent scores of 4 or more were observed in all women at baseline, and any STI or vaginal candidiasis in 78%.
Targeted antibiotic or antifungal treatment was given to women with Nugent scores of 4 or higher at baseline, but only 25% were BV negative at 6 weeks, and this rate did not change at 12 weeks.
These results indicated frequent treatment failure and persistent BV, associated with an increase in cell-associated inflammatory response, following MDZ treatment. Investigators recommended alternative strategies such as pre- and pro-biotics, vaginal microbiome transplantation, and phage endolysins be used to improve Lactobacillus representation.
Qulu WP, Mzobe G, Mtshali A, et al.Metronidazole treatment failure and persistent BV lead to increased frequencies of activated T- and dendritic-cell subsets. Microorganisms. 2023;11(11):2643. doi:10.3390/microorganisms11112643