Genital microbiota of women using a 90 day tenofovir or tenofovir and levonorgestrel intravaginal ring in a placebo controlled randomized safety trial in Kenya
Authors: Dabee Smritee , Mugo Nelly , Mudhune Victor , McLellan-Lemal Eleanor , Peacock Sue , O’Connor Siobhan , Njoroge Betty , Nyagol Beatrice , Thurman Andrea R. , Ouma Eunice , Ridzon Renee , Wiener Jeffrey , Haugen Harald S. , Gasper Melanie , Feng Colin , Allen Shannon A. , Doncel Gustavo F. , Jaspan Heather B. , Heffron Renee ,   Kisumu Combined Ring Study Team, Mugo Nelly R. , Mudhune Victor , Heffron Renee , McLellan-Lemal Eleanor , O’Connor Siobhan , Doncel Gustavo F. , Thurman Andrea R. , Njoroge Betty , Nyagol Beatrice , Ouma Eunice , Ndivo Richard , Oguta Maxcine , Opon Haynet , Awili Dorine , Mithika Anne , Chavangi Epines , Oruko Jecinter , Okanda John , Ogendo Arthur , Ayuo Elizabeth , Odipo Evans , Sewe Vitalis , Kerubo Boaz , Mbeda Calvin , Awuonda Eucabeth , Odero Isdorah , Anyango Emily , Mimba Erica , Oloo Fredrick , Odipo Richard , Opollo Valarie , Kerubo Emily , Omondi Fredrick , Gende Angelica , Wandera Kelvin , Juma Carolyne , Were Alice , Ogutu Phoebe , Aremo Susan , Madiega Philister , Ogando Daniel , Arego Judith , Otieno Margaret , Akello Rosemary , Ondeng’e Ken , Omoro Teresa , Amondi Caren , McCarthy Kimberly , Ridzon Renee , Morrison Susan , Krows Meighan , Celum Connie , Ouattara Abenan L. , Yousefieh Nazita , Schwartz Jill , Matthews Allison , Allen Shannon , Russell Elizabeth , Near Karen , Wiener Jeffrey , Samandari Taraz , Deaton Stacie R. , Claypool Lee , Betts Josh E. , Haaland Richard E. , Martin Amy , Fountain Jeffrey , Jacot Terry A. , Erikson David , Blue Steven W. , Jaspan Heather , Dabee Smritee , Feng Colin , Gasper Melanie , Remington Barrett , Frank Bruce L. , Isoherranen Nina , Haugen Harald , Baeten Jared , Thomas Katherine , Kourtis Athena , Tepper Naomi , Ondrejcek Lisa , Williams Angela , Johnson Matt , Jiang Joe , Peacock Sue , Donnell Deborah 
Published: July 2022

In a phase-IIa trial, we investigated the influence of 90 days continuous-delivery tenofovir (TFV) intravaginal rings (IVRs) with/without levonorgestrel (LNG) on the genital microbiota of Kenyan women. Eligible women (n = 27; 18–34 years; negative for HIV, sexually transmitted infections, and Amsel-bacterial vaginosis) were randomized 2:2:1 to use of IVRs containing TFV, TFV/LNG, or placebo. Using vaginal wall and IVR swabs at IVR insertion and removal, the genital microbial composition was determined using 16S rRNA gene sequencing. The presence ofCandidaspp. was determined using qPCR. The vaginal total bacterial burden appeared to decrease with TFV and TFV/LNG IVR use (log100.57 and log100.27 decrease respectively; p > 0.05). The TFV/LNG IVR was more ‘stabilizing’: 50% of the participants’ microbiota community state types remained unchanged and 50% shifted towards higherLactobacillusabundance. Specifically, TFV/LNG IVR use was accompanied by increased abundances ofLactobacillus gasseri/hominis/johnsonii/taiwanensis(16.3-fold) andL. fermentum/reuteri/vaginalis(7.0-fold; all p < 0.01). A significant shift in the overall microbial α-diversity or β-diversity was not observed for either IVR, and IVR use did not influenceCandidaspp. prevalence. TFV/LNG and TFV IVRs did not adversely affect the genital microbiota and are safe to use. Our findings support further studies assessing their efficacy in preventing HIV/HSV-2 and unintended pregnancies.