Circumcision in men and the prevention of HIV infection: a 'meta-analysis' revisited

There is debate on the role of male circumcision in HIV transmission. Most case-control and cohort studies from Africa have shown an association between a lack of circumcision and an increased risk of HIV infection in men. The evidence is conflicting, however, with cross-sectional surveys from Tanzania and Rwanda either showing no relationship or an association in the opposite direction. A recent review and meta-analysis of the literature concluded that the risk of HIV infection was lower in uncircumcised men (combined odds ratio 0.94, 95% confidence interval 0.89 to 0.99). However, the analysis was performed by simply pooling the data from 33 diverse studies, which is an inappropriate method for combining studies. We re-analysed the data, stratifying by study, and found that an intact foreskin was associated with an increased risk of HIV infection: combined odds ratio 1.43 (1.32 to 1.54) with a fixed effect model and 1.67 (1.25 to 2.24) with a random effect model. There was significant between-study heterogeneity (P < 0.0001) which was partly explained by stronger associations in studies in high-risk groups. The results from this re-analysis thus support the contention that male circumcision may offer protection against HIV infection, particularly in high-risk groups where genital ulcers and other STDs 'drive' the HIV epidemic. A systematic review is required to clarify this issue. Such a review should be based on an extensive search for relevant studies, published and unpublished, and should include a careful assessment of the design and methodological quality of studies. Much emphasis should be given to the exploration of possible sources of heterogeneity. In view of the continued high prevalence and incidence of HIV in many countries in sub-Saharan Africa, the question of whether circumcision could contribute to prevent infections is of great importance, and a sound systematic review of the available evidence should be performed without delay.

[1]  G. Smith,et al.  1 Rationale, potentials, and promise of systematic reviews , 2001 .

[2]  N. Nagelkerke,et al.  Analysis of the scientific literature on male circumcision and risk for HIV infection. , 1999, International journal of STD & AIDS.

[3]  B. Chohan,et al.  Effect of circumcision on incidence of human immunodeficiency virus type 1 and other sexually transmitted diseases: a prospective cohort study of trucking company employees in Kenya. , 1999, The Journal of infectious diseases.

[4]  N. Sewankambo,et al.  Age of male circumcision and risk of prevalent HIV infection in rural Uganda. , 1999, AIDS.

[5]  R. S. Howe,et al.  Circumcision and HIV Infection: Review of the Literature and Meta-Analysis , 1999 .

[6]  F. Hodges,et al.  Immunological functions of the human prepuce. , 1998, Sexually transmitted infections.

[7]  N. Black,et al.  The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. , 1998, Journal of epidemiology and community health.

[8]  G. Smith,et al.  Meta-analysis Spurious precision? Meta-analysis of observational studies , 1998, BMJ.

[9]  Christopher H Schmid,et al.  Summing up evidence: one answer is not always enough , 1998, The Lancet.

[10]  George Davey Smith,et al.  Meta-analysis: Principles and procedures , 1997, BMJ.

[11]  G. Smith,et al.  Meta-analysis: Potentials and promise , 1997, BMJ.

[12]  M. Tramèr,et al.  Impact of covert duplicate publication on meta-analysis: a case study , 1997, BMJ.

[13]  C. Lengeler,et al.  Language bias in randomised controlled trials published in English and German , 1997, The Lancet.

[14]  J. Newell,et al.  Sexual behaviour patterns and other risk factors for HIV infection in rural Tanzania: a case–control study , 1997, AIDS.

[15]  J. T. Boerma,et al.  Male circumcision and susceptibility to HIV infection among men in Tanzania , 1997, AIDS.

[16]  J. Last,et al.  Making the Dictionary of Epidemiology. , 1996, International journal of epidemiology.

[17]  S. Duffy,et al.  Development of a scoring system to judge the scientific quality of information from case-control and cohort studies of nutrition and disease. , 1995, Nutrition and cancer.

[18]  E. Karita,et al.  Male circumcision, sexually transmitted disease, and risk of HIV. , 1995, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[19]  S G Thompson,et al.  Systematic Review: Why sources of heterogeneity in meta-analysis should be investigated , 1994, BMJ.

[20]  S Shapiro,et al.  Meta-analysis/Shmeta-analysis. , 1994, American journal of epidemiology.

[21]  S. Moses,et al.  The Association Between Lack of Male Circumcision and Risk for HIV Infection: A Review of the Epidemiological Data , 1994, Sexually transmitted diseases.

[22]  A. Saah,et al.  Risk Factors Associated with Prevalent HIV-1 Infection among Pregnant Women in Rwanda , 1994 .

[23]  A. Nunn,et al.  Risk factors for HIV‐1 infection in adults in a rural Ugandan community: a case‐control study , 1994, AIDS.

[24]  T. Mertens,et al.  Male circumcision: a role in HIV prevention? , 1994, AIDS.

[25]  A. Hoosen,et al.  Genital ulcer disease: accuracy of clinical diagnosis and strategies to improve control in Durban, South Africa. , 1994, Genitourinary medicine.

[26]  I. Chalmers The Cochrane Collaboration: Preparing, Maintaining, and Disseminating Systematic Reviews of the Effects of Health Care , 1993, Annals of the New York Academy of Sciences.

[27]  N. O’Farrell,et al.  Soap and water prophylaxis for limiting genital ulcer disease and HIV-1 infection in men in sub-Saharan Africa. , 1993, Genitourinary medicine.

[28]  R. Hayes,et al.  The epidemiology of HIV‐1 infection in urban areas, roadside settlements and rural villages in Mwanza Region, Tanzania , 1992, AIDS.

[29]  T C Chalmers,et al.  Getting to grips with Archie Cochrane's agenda. , 1992, BMJ.

[30]  A. Phillips,et al.  Confounding in epidemiological studies: why "independent" effects may not be all they seem. , 1992, BMJ.

[31]  F. Plummer,et al.  Long distance truck-drivers: 1. Prevalence of sexually transmitted diseases (STDs). , 1991, East African medical journal.

[32]  A. Phillips,et al.  How independent are "independent" effects? Relative risk estimation when correlated exposures are measured imprecisely. , 1991, Journal of clinical epidemiology.

[33]  N. Nagelkerke,et al.  Geographical patterns of male circumcision practices in Africa: association with HIV seroprevalence. , 1990, International journal of epidemiology.

[34]  R. Brunham,et al.  FEMALE TO MALE TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1: RISK FACTORS FOR SEROCONVERSION IN MEN , 1989, The Lancet.

[35]  J. Bongaarts,et al.  The relationship between male circumcision and HIV infection in African populations. , 1989, AIDS.

[36]  T C Chalmers,et al.  A comparison of statistical methods for combining event rates from clinical trials. , 1989, Statistics in medicine.

[37]  C. Begg,et al.  Publication bias and dissemination of clinical research. , 1989, Journal of the National Cancer Institute.

[38]  P. Piot,et al.  Human immunodeficiency virus infection among men with sexually transmitted diseases. Experience from a center in Africa. , 1988, The New England journal of medicine.

[39]  C. Mulrow The medical review article: state of the science. , 1987, Annals of internal medicine.

[40]  R. Simes,et al.  Confronting publication bias: a cohort design for meta-analysis. , 1987, Statistics in medicine.

[41]  Finkel Aj A possible explanation for heterosexual male infection with AIDS. , 1986 .

[42]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[43]  R. Peto,et al.  Beta blockade during and after myocardial infarction: an overview of the randomized trials. , 1985, Progress in cardiovascular diseases.