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. 2022 Oct 28;77(11):3180-3186.
doi: 10.1093/jac/dkac300.

A post-mortem analysis of tenofovir, lamivudine, efavirenz and fluconazole penetration in female genital tissues

Fan Wang  1 , Olivie C Namuju  2 , Katelyn A Pastick  3   4 , Kizito Abdusalaamu  2 , Usha Mishra  1 , Lindsey Collins  1 , David R Boulware  3 , Robert Lukande  5 , David B Meya  3   5 , Melanie R Nicol  1
Affiliations

A post-mortem analysis of tenofovir, lamivudine, efavirenz and fluconazole penetration in female genital tissues

Fan Wang et al. J Antimicrob Chemother. .

Abstract

Background: Optimal penetration of anti-infectives in the female genital tract (FGT) is paramount in the treatment and prevention of infectious diseases. While exposure of anti-infectives in lower FGT tissues (e.g. cervix, vagina) has been described, little data exist on upper genital tissues (e.g. ovary, uterus).

Methods: Autopsies were performed and post-mortem tissues were collected within 24 h of death for female participants with advanced HIV in Uganda (n = 27). Tenofovir, lamivudine, efavirenz and fluconazole concentrations were measured using LC-MS/MS in plasma, ovarian, uterine, cervical and vaginal tissues. Tissue penetration was calculated as tissue-to-plasma concentration ratios (TPRs).

Results: TPRs of tenofovir, lamivudine and fluconazole were highest in vaginal tissue (medians 1.86, 1.83 and 0.94, respectively), while the TPR of efavirenz was highest in ovarian tissue (median 0.65). With cervix as a reference compartment, vaginal TPRs were significantly higher than cervical for all four drugs; TPRs of efavirenz in uterine and ovarian compartments were also significantly higher than cervical. Most of the post-mortem FGT samples had a TPR of greater than 1 for tenofovir and lamivudine, while less than 50% had a TPR of greater than 1 for both efavirenz and fluconazole.

Conclusions: Penetration of anti-infectives was not homogeneous among the FGT compartments. Approximately 70% of FGT tissues had a TPR of greater than 1 for tenofovir and lamivudine, favouring the prevention of local HIV replication and transmission in the FGT.

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Figures

Figure 1.
Figure 1.
Concentrations of tenofovir (a), lamivudine (b), efavirenz (c) and fluconazole (d) in ovarian, uterine, cervical and vaginal tissue. In each plot, points with the same colour represent the same individual. *P < 0.05; **P < 0.01; ***P < 0.005. TFV, tenofovir; 3TC, lamivudine; EFV, efavirenz; FLC, fluconazole. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.
See this image and copyright information in PMC

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