Genital Inflammation Raises HIV Risk in South African WomenGenital inflammation markers linked to higher risk of HIV infection
Journal of acquired immune deficiency syndromes (1999)Published October 5, 2026Study authors: Osman Farzana, Yende-Zuma Nonhlanhla, Zewotir Temesgen, Naicker Nivashnee, Liebenberg Lenine J P, Ts…PubMed ↗DOI ↗Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease
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Key Takeaway
Cervicitis and abnormal discharge strongly predict HIV acquisition in women.
A randomized controlled trial followed 774 HIV-uninfected women in South Africa for 34 months to assess whether clinical and immunological measures of genital inflammation predict HIV acquisition. The study focused on cytokine profiles and clinical genital abnormalities as potential early indicators of risk.
Abnormal genital discharge was significantly associated with increased HIV acquisition, with an adjusted hazard ratio of 2.67 (95% CI: 1.14 to 6.23; P = 0.024). Cervicitis showed an even stronger association, with an adjusted hazard ratio of 10.34 (95% CI: 2.46 to 43.65; P = 0.001).
When both clinical and immunological inflammation were present, women had the highest risk of HIV acquisition. The adjusted hazard ratio was 2.08 for clinical inflammation (95% CI: 1.10 to 3.91; P = 0.022) and 2.46 for immunological inflammation (95% CI: 1.21 to 5.03; P = 0.013).
These findings suggest that clinical signs may serve as practical early indicators of HIV risk, while cytokine profiles offer more sensitive measures of underlying inflammation. However, clinical signs and cytokine profiles are not the only predictors or measures of inflammation, and causality cannot be inferred from these associations.
No safety data, limitations, or funding information were reported. The results highlight the potential utility of genital inflammation markers in HIV prevention strategies.
How this fits prior evidence
How this fits prior evidence: This study addresses a gap in identifying specific clinical markers of risk for HIV acquisition. While previous coverage discussed the efficacy and safety of various regimens like Efavirenz, F/TAF, and Tenofovir Disoproxil Fumarate in maternal ART, this study focuses on the role of local inflammation as a predictor of acquisition in HIV-uninfected women.
For many women, the risk of contracting HIV is tied to the health of the vaginal environment. A study in South Africa followed 774 women to see how physical signs of inflammation affected their risk of infection. The researchers looked at both visible symptoms and internal immune markers.
They found that certain physical signs were strong indicators of risk. For example, women with abnormal genital discharge had a much higher risk of HIV infection. Even more significant was the finding on cervicitis, which is inflammation of the cervix. Women with this condition showed a very high risk of infection.
While clinical signs like discharge are easy for doctors to see, the study also looked at cytokine profiles. These are measures of the immune system's response. Both the visible signs and the internal immune markers showed that inflammation makes it easier for HIV to take hold. These findings suggest that physical symptoms can serve as practical early warnings for doctors and patients.
What this means for you:
Visible signs of genital inflammation, like discharge or cervicitis, are linked to a higher risk of HIV infection.
Common questions
What physical signs were linked to a higher risk of HIV?
The study found that abnormal genital discharge and cervicitis (inflammation of the cervix) were both linked to a higher risk of HIV infection. Specifically, cervicitis was associated with a much higher risk, while discharge also showed a significant link to increased infection rates.
What is the difference between clinical and immunological inflammation?
Clinical inflammation refers to visible signs like discharge or cervicitis. Immunological inflammation refers to cytokine profiles, which are internal measures of the immune system's response. Both types of inflammation were found to be linked to a higher risk of HIV infection.
How can these findings help in medical practice?
Clinical signs like discharge can provide practical, early indicators of risk for doctors. While internal immune measures are very sensitive, the visible signs of inflammation can help identify women who may be at higher risk for HIV infection.
BACKGROUND: Inflammation in the female genital tract is a key risk factor for HIV acquisition, but it remains unclear whether clinical or immunological measures best predict risk. We aimed to compare HIV acquisition among women with clinically and/or immunologically defined inflammation.
SETTING: HIV-uninfected women enrolled in the CAPRISA 004 tenofovir gel randomized controlled trial in South Africa were followed for up to 34 months.
METHODS: We analyzed data from 889 women, with cytokine measurements available for 774 participants. Clinical genital abnormalities were assessed at scheduled visits, and 9 cytokines were measured in cervicovaginal lavage samples. HIV incidence was compared across categories of clinical and immunological inflammation using time varying Cox proportional hazards models, adjusting for relevant covariates.
RESULTS: Immunological inflammation, defined as ≥9 elevated cytokines, was present in 18% (140/774) of women. Among specific clinical signs, abnormal genital discharge (adjusted hazard ratio: 2.67, 95% confidence interval [CI]: 1.14 to 6.23, P = 0.024) and cervicitis (adjusted hazard ratio: 10.34, 95% CI: 2.46 to 43.65, P = 0.001) were significantly associated with increased HIV acquisition. Women with both clinical and immunological inflammation had the highest risk of HIV acquisition, with adjusted hazard ratios of 2.08 (95% CI: 1.10 to 3.91, P = 0.022) and 2.46 (95% CI: 1.21 to 5.03, P = 0.013), respectively.
CONCLUSIONS: Clinical and immunological definitions of inflammation were each independently associated with increased HIV acquisition risk and combined, they reflected greater susceptibility. These findings highlight the important role of genital inflammation in women's HIV susceptibility, suggesting that clinical signs may provide practical early indicators of risk even as cytokine profiles provide more sensitive measures of underlying inflammation.
