HIV-2 and natural protection against HIV-1 infection.

Karmn Travers et al. report that infection with HIV-2, an apparently less virulent strain of the human immunodeficiency virus (HIV), provided natural protection, estimated at approximately 70%, against infection with HIV1 in a cohort of female sex workers in Senegal (1. This finding rests on the significantly lower HIV1 incidence rate over a 9-year period among HIV2-infected women [1.06 per 100 personyears of observation (PYO) in tables 1 and 2 of the report (1)] than among HIV-seronegative women [shown as 2.53 per 100 PYO in table 1 but 2.45 per 100 PYO in table 2 of the report (1)]. However, in a 1994 paper (2) the same research group reported an HIV1 incidence rate of 1.11 per 100 PYO in the same general population of HIV-seronegative female sex workers followed over roughly the same period. Had the HIV1 incidence rate among seronegative women in the 1995 report (1) been similar to that reported the year before, no reduced HIV-1 incidence would have been found among HIV-2-infected women relative to uninfected women, and therefore there would have been no suggestion of natural protection. A comparison of the data from these two papers (1, 2) (Table 1) shows that, while the numbers of women seroconverting annually in the two studies were identical through 1989 and similar in 1990 and 1991 (differences in 1992 and 1993 were presumably due to the longer follow-up period in the later paper), the 1995 report (1) includes only about half as many seronegative women (618 women contributing 2410 PYO) as reported in the earlier paper (2) (1277 women contributing 4141 PYO). The 1994 paper (2) appears to report on all initially HIV-seronegative female sex workers enrolled in the Dakar study clinic. The time observed before their latest serologic test served as the denominator, while the number of seroconversions in the group was the numerator for computing the HIV1 incidence rate. The 1995 report (1) followed only a subset of the earlier study population, limited to those women with HIV-1 or HIV-2 infection (apparently including both initially prevalent cases and cases incident during follow-up) along with two randomly selected seronegative women for each infected woman, matched on the basis of age, nationality, and number of years of registered prostitution. This procedure seems to have reduced the number of seronegative women followed up (and the corresponding PYG) by a factor of about two, yet included virtually all the seronegative women who became HIV-1 positive. It seems highly unlikely to us that truly random sampling would have brought all the seroconverters into the smaller group, and a selection bias favoring seroincident HIV1 cases may have occurred. Such a bias would artifactually elevate the HIV1 incidence rate in the seronegative group, giving by comparison the appearance of a lower HIV-1 incidence in the HIV-2 group. Because of this uncertainty, the evidence is currently insufficient to suggest that HIV-2 infection protects against HIV1.We hope Travers et al. will clarify how virtually all the seroconverters from the larger study population were selected into their seronegative comparison group. To minimize the effect of potential selection biases, we would encourage the authors to recalculate the HIV1 incidence rates in their unique and valuable study population