PrEP (Pre-Exposure Prophylaxis) is an established HIV prevention strategy for individuals at substantial risk of acquiring the virus. The regimen, typically a combination of two antiretroviral drugs, is highly effective at stopping the virus from establishing a permanent infection. When taken consistently, PrEP offers a high degree of protection for women. The perception that PrEP “does not work” is a misunderstanding rooted in unique biological and adherence challenges, specifically how the drug is processed to protect the female reproductive tract.
Drug Concentration in Female Reproductive Tissue
The perception of lower efficacy stems from the pharmacokinetics of the drug within the female genital tract (FGT) tissues. When oral PrEP is taken, the active drug components must travel through the bloodstream to reach the mucosal tissue—the vagina and cervix—where HIV exposure occurs. The active drug, tenofovir diphosphate, must saturate the target immune cells to create a protective barrier.
Achieving protective concentrations in the FGT requires a longer period of consistent daily dosing compared to rectal tissue. This is because the vaginal and cervical tissues form a larger, more complex mucosal reservoir. It takes approximately 20 days of daily PrEP use for a woman to reach the maximum protective drug concentration in these tissues.
The concentration of active drug needed for protection in the FGT is roughly double that required in the rectum. This biological reality means that any interruption in the daily dosing schedule is more consequential for women. Protective drug levels decay more quickly in the FGT, rapidly leaving the tissue vulnerable to infection if a dose is skipped.
The Essential Role of Consistent Adherence
The most significant factor driving differences in observed efficacy rates is adherence—the consistency with which the daily pill is taken. Because the FGT requires a sustained, high concentration of the drug, missing doses quickly drop the drug level below the therapeutic threshold. This contrasts with rectal tissue, where drug levels remain protective longer after a missed dose.
In studies with low adherence, the overall efficacy rate for the female cohort was also low. Taking four doses per week provides an estimated 84% reduction in HIV incidence, while seven doses per week provides an estimated 96% protection. This demonstrates that near-perfect daily adherence is necessary to maintain drug saturation in the FGT.
Real-world factors often interfere with maintaining the daily dosing schedule. Issues such as perceived stigma, privacy concerns, cost, or lack of self-perceived risk contribute to inconsistent pill-taking. Women may stop taking the pill when not actively having sex, failing to account for the 20-day loading period and the rapid decay of protection.
Interpreting PrEP Efficacy Data
Early clinical trials involving women often produced mixed or low overall efficacy results, fueling the misconception that PrEP was ineffective. Trials like FEM-PrEP and VOICE reported low effectiveness, but subsequent analysis showed the issue was adherence, not the drug’s mechanism. In the VOICE trial, drug level testing showed only about 29% of participants had detectable drug levels.
When data were re-analyzed based on objective measures of drug concentration, a clear pattern emerged. In trials where women had detectable drug levels, signifying good adherence, the efficacy rate consistently rose to over 90% risk reduction. The Partners PrEP study demonstrated a 94% risk reduction among women with detectable drug in their plasma.
These findings confirm that PrEP is highly effective for women. The low overall efficacy reported was a statistical artifact of pooling data from participants who were not taking the pill consistently. The failure was due to drug levels being too low to provide protection, which is a matter of adherence.
Non-Daily and Alternative Prevention Methods
Recognizing the challenges associated with daily adherence and FGT pharmacokinetics, alternative prevention methods have been developed. These methods aim to bypass the need for daily oral pill-taking or deliver the drug directly to the point of risk.
One female-controlled option is the Dapivirine vaginal ring (DVR), a flexible silicone ring inserted into the vagina that slowly releases dapivirine over one month. Delivering the drug locally, directly to the FGT tissue, largely eliminates the systemic challenge of achieving saturation through oral administration. Clinical trials found that the DVR reduced the risk of HIV acquisition by approximately 35% overall.
A different approach is long-acting injectable PrEP, which uses cabotegravir (CAB-LA) administered every two months. This method solves the daily adherence challenge by providing sustained, systemic protection. Injectable cabotegravir was shown to be superior to daily oral PrEP in preventing HIV among women, demonstrating high effectiveness.