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Foreskin surface area and HIV acquisition in Rakai, Uganda (size matters)
Global Health Sciences Literature Digest
Published June 03, 2010
Journal Article

Kigozi G, Wawer M, Ssettuba A. Foreskin surface area and HIV acquisition in Rakai, Uganda (size matters). AIDS. 2009 Oct 23;23(16):2209-13.

In Context

Numerous studies have shown that male circumcision reduces a man's risk of becoming HIV infected by 50%-60%.(1, 2) Removing the foreskin may reduce the rate of genital ulcer disease and decrease exposure of mucosa and target cells to HIV-infected fluids.(3)

Objectives

To determine whether foreskin surface area was associated with HIV acquisition among men before circumcision

Setting

A rural area in southwest Uganda

Design

Retrospective analysis of a longitudinal cohort study, with baseline data from subsequent randomized trials

Population/Sample

Men initially uninfected with HIV and aged 15-49 years were followed for up to four years and then enrolled into circumcision trials; only men who were not lost to follow-up were included in this analysis.

Methods

Data were analyzed from HIV-negative men enrolled in the Rakai Community Cohort Study (RCCS) and followed for up to four years. Men were then randomized to receive immediate circumcision (sleeve method) or have circumcision delayed by two years.(4) The foreskin surface area was measured immediately after surgery. HIV incidence was calculated until time of seroconversion or circumcision.

Results

Of 965 men included in this analysis, 48 seroconverted prior to circumcision (1.27 cases per 100 person years [p100py]). The mean foreskin surface area was significantly larger among men who seroconverted compared to those who did not (43.3 cm2 vs. 36.8 cm2; P=0.001), as well as among older men aged 25-49 years compared with men 15-24 years old. HIV incidence increased as foreskin size increased, from 0.80 p100py) among men with the smallest foreskin area (≤26.3 cm2) to 2.48 p100py among those with the largest foreskin area (>44.6 cm2), with an adjusted incident risk ratio (aIRR) of 2.37 (95% confidence interval [CI]: 1.05-5.31) for men with the largest foreskin size relative to those with the smallest. Other factors independently associated with HIV incidence included having at least a secondary education, and having two or more sex partners in the last year.

Conclusion

This study strongly suggests that larger foreskin size is a risk factor for HIV infection among men who are not circumcised.

Quality Rating

This was a good study, and the significant trend of increasing HIV incidence with an increasing quartile of foreskin area further supports the conclusions. However, repeated measurements were not performed to assess measurement variability, which could be important because foreskin tissue is not uniform in shape.

Programmatic Implications

This study supports the biological hypothesis that the foreskin is a tissue vulnerable to HIV acquisition, possibly due to large numbers of target cells, or to micro-tears during sexual intercourse.(3) Results also suggest that residual foreskin tissue be avoided during surgery. This is more likely to occur with the forceps-guided procedure compared to either the dorsal slit or sleeve procedures, although the size of residual tissue is usually extremely small.(5) This is the only study evaluating these associations, and further data are needed to substantiate these findings.

References

  1. Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med 2005;2:e298.
  2. Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomized controlled trial. Lancet 2007;369:643-56.
  3. Szabo R, Short RV. How does male circumcision protect against HIV infection? BMJ 2000; 320:1592-4.
  4. Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomized trial. Lancet 2007;369:657-66.
  5. WHO, UNAIDS, JHPIEGO. Manual for male circumcision under local anaesthesia, version 2.5c. World Health Organization. 2008;5-16. Abstract not available.