The Effectiveness of Condoms in Reducing Heterosexual Transmission of HIV.(Statistical Data Included)

Heterosexual intercourse is the primary mode of HIV infection worldwide.[1] In the United States, male homosexual contact and intravenous drug use account for the majority of HIV infections, but transmission via heterosexual contact continues to increase. Heterosexual contact with an infected partner is the greatest risk factor for women and, consequently, for their newborn children. In 1988, 2% of male AIDS cases and 30% of female cases reported in the United States were attributed to heterosexual contact.[2] By 1998, this percentage had risen to 7% for men and 38% for women.[3]

Although new treatments appear promising for retarding the progression of HIV-related disease, prevention remains the most effective weapon against the epidemic. Recommendations for the prevention of sexually transmitted HIV infection include abstinence, long-term monogamy with a seronegative partner, a limited number of lifetime sexual partners and condom use for each and every act of intercourse.[4] The use of condoms is recommended for individuals who have multiple partners, who have a primary partner who is infected, or who have a partner whose serostatus is unknown,[5] although the absolute amount of protection they provide has not been accurately established.

The effectiveness of the condom as a contraceptive provides insight into its usefulness as a barrier device capable of preventing HIV transmission. Defined as the proportionate reduction in pregnancies caused by use of a contraceptive method, effectiveness is estimated as one minus the ratio of two failure rates. The failure rate ratio is calculated by dividing the pregnancy rate associated with use of a contraceptive method by the rate related to no method use for a given time period.[6] The likelihood of becoming pregnant during the first year of condom use ranges from 2.6% to 15.8%.[7] The likelihood of pregnancy in a population not practicing contraception is estimated from groups such as the Hutterites, and is often assumed to be 85%.[8] These probabilities can be transformed into rates,(*) providing an estimate of condom effectiveness for preventing pregnancy of 90.7% to 98.6%.

The effectiveness of condoms in reducing HIV may be estimated in the same way as for contraception. For HIV, the failure rate ratio is calculated by dividing the seroconversion rate among couples always using condoms by the rate among couples never using condoms. A comparison group of condom nonusers is essential to determine the reduction in HIV incidence that is due to condom use. The best measure of condom efficacy is obtained by comparing monogamous, serodiscordant couples (i.e., those who differ in their HIV infection status) who always use condoms during penetrative vaginal intercourse with those who never do. Since HIV serodiscordant couples cannot ethically be assigned at random to "always" and "never" use condoms, estimates must be obtained from observational studies. Unfortunately, observational studies may be biased by an unequal distribution of HIV risk factors across study categories.

For both contraception and HIV prevention, condom failure has two sources: user failure and method failure. User failure includes nonuse and incorrect use, and is attributed to the person using the condom. Method failure is the absolute, theoretical failure inherent in the device, and is independent of the user. User failure varies per person and per contact, while method failure is assumed to be constant. It is impossible to measure absolute method failure, since it is confounded with user failure.

Condom failure due to nonuse, incorrect use, breakage and slippage may occur for both HIV prevention and birth control.[9] In several recent in vivo trials measuring failure due to breakage and slippage, rates have varied from 0.5% to 6.7% for breakage and 0.1% to 16.6% for slippage,[10] Quality control standards set by the Food and Drug Administration allow four out of 1,000 condoms in any given batch to leak water.[11] In vitro trials have reported HIV leakage in 0-100% of the condoms tested,[12] with all but one brand[13] between 0.0% and 54%.

Various estimates of the condom's effectiveness at reducing heterosexual transmission of HIV are available from studies of serodiscordant couples. In order to obtain a single overall estimate of effectiveness, we present a meta-analysis of those results. An initial attempt[14] to do so was flawed because it aggregated studies with varying definitions of condom use, directions of transmission, study designs and types of index cases. A subsequent report[15] controlled for the direction of transmission, but did not remove the sometimes or occasional users of condoms from among the never-users, and also did not control for study design.

An additional source of bias occurs in recent estimates of HIV incidence among condom nonusers. Because condom use is no longer independent of HIV risk factors, as it was prior to the AIDS era, the association between condom use and seroconversion is biased by the self-selection of individuals into the groups always or never using condoms. Notably, there is a potential difficulty with using groups of condom nonusers in recent studies of serodiscordant couples as a control or comparison group: They may not be "equivalent" to the consistent condom users in all aspects except condom use. Thus, in this article, we examine transmission rates by study design, study date, direction of transmission, source of infection in the index case and condom usage group. Condom effectiveness is calculated from two separately estimated transmission rates: the transmission rate among those who always used condoms and the transmission rate among different populations of never-users.

Methods

We reexamine in vivo evidence of condom efficacy in reducing heterosexually transmitted HIV. Peer-reviewed articles and letters to the editor published prior to July 1999 were located using MEDLINE, AIDSLINE and reference lists. Studies had to meet throe criteria for inclusion: They had to have focused on sexual transmission of HIV among serodiscordant heterosexual couples having penetrative sexual intercourse; they had to have determined HIV status by serology; and they had to have inquired about condom usage. Studies focusing on commercial sex workers were not considered because of the uncertainty of exposure.

A meta-analysis is a quantitative summary of results across studies that address the same research question, so it is important that equivalent information is available for analysis. To ensure that comparisons were made across equivalent variables, we classified and combined previous research by study design (cross-sectional or longitudinal), date of subject enrollment and direction of transmission (male-to-female, female-to-male or unknown).

Condom usage was defined as always, sometimes and never. The always-use category indicated that a condom was used for 100% of penetrative acts of vaginal intercourse. The never-use category indicated that condoms were not used during any acts of vaginal intercourse (0%). The sometimes-use category included intermediate estimates of usage (1-99%) and combinations of never-use and sometimes-use (0-99%) or always-use and sometimes-use (1-100%). We based our classification of condom use into these three categories upon published descriptions. Consensus between the authors of this report as to the coding of each study's data was necessary, and we requested clarifications directly from the authors.

Because aggregations are most reliable when made across homogeneous sample estimates, we used a chi-square test to determine homogeneity among the proportions of HIV seroconversions across different subgroups of studies, and to check for trends across time. Incidence was estimated from the number of seroconversions and the person-years of observation. We obtained an overall estimate of incidence using a weighted-average of results from a series of studies (the total number of seroconversions divided by the total person-years of exposure).

Confidence intervals for proportions were constructed with the binomial distribution,[16] and confidence intervals for incidence (with time as the unit of analysis) were determined using the Poisson distribution.[17] Effectiveness was calculated by taking one minus the ratio of HIV incidence among those who always used condoms to that of those who never used condoms. We calculated best-case and worst-case scenarios for effectiveness using upper and lower bounds of the confidence intervals for the two seroconversion rates.

Results

The Studies

Thirty-seven studies met the inclusion criteria. Eight studies were excluded because the inquiry on condom usage was not sufficiently detailed, so that neither an always-nor a never-use category could be ascertained.[18] Of the remaining studies, four reports on the same cohort were eliminated from the analysis.[19] In the case of duplicate reports on the same cohort, the report with the most detailed condom usage definition and the largest sample size was selected.

After these exclusions, 25 studies remained for analysis. Thirteen cross-sectional studies[20] contained 12 samples describing male-to-female transmission and four samples of female-to-male transmission (Table 1, page 273). Twelve longitudinal studies[21] contained eight samples describing male-to-female transmission, four samples of female-to-male transmission and four samples that did not state the direction of transmission (Table…