Sexual Transmission During the Incubation Period of Primary HIV Infection

To the Editor: The concept that peak viremia during primary human immunodeficiency virus (HIV) infection (PHI) could be associated with concurrent high-level genital shedding^{1 - 2} has led to the hypothesis that individuals with PHI are highly infectious. This hypothesis would in part explain rapid epidemic spread in populations³ and would suggest that PHI is an important target for public health intervention. We sought to establish that such transmission occurs and to examine the window of infectiousness during PHI.

We investigated 5 cases drawn from 4 university hospital clinics, in whom sexual transmission was suspected to have occurred between an individual with documented PHI and a sexual partner who later developed documented PHI. We defined PHI as p24 antigen positivity, RNA and/or DNA positivity, enzyme-linked immunosorbent assay negativity, or 2 or fewer bands on Western blot within 30 days. Other risk factors for transmission were excluded. Each transmission pair was confirmed by phylogenetic analysis of HIV reverse transcriptase sequences with bootstrap values greater than 99/100 using Fitch-Margoliash and least squares methods (data not shown).

Transmission was woman-to-man in couple 1; man-to-woman in couples 2, 3, and 4; and man-to-man in couple 5. Couples 1 and 2 reported frequent, regular intercourse during periods of possible sexual exposure, but couples 3, 4, and 5 recalled only single sexual contacts with one another during the time of possible transmission. Except in the case of couple 2, all transmitters explained their own infection by identifying specific high-risk sexual exposures with other partners. In couples 1 through 4, transmitters infected a steady sexual partner via penile-vaginal intercourse; in couple 5, transmission was via insertive anal and oral sex. Seminal plasma HIV RNA concentrations, examined in couple 5 only, were higher than commonly seen in chronic infection¹ for both transmitter and infected partner (5.7 and 5.9 log copies/mL, respectively). Other sexually transmitted infections were identified in couple 1 (genital herpes simplex virus [HSV] and chlamydia) and in couple 5 (genital HSV and early syphilis); in couple 4, the transmitter had a sterile inguinal abcess.

The timing of events for each couple is shown in Figure 1. The single reported exposure occurred before the transmitter's onset of symptoms for couples 4 (day −2) and 5 (day −7). There were multiple sexual exposures for couple 1, but all occurred prior to day +2 after the transmitter's onset of symptoms. A single exposure occurred on day +7 after symptom onset in couple 3. Observed incubation periods for transmitter 1, infected partner 3, and infected partner 4 were 20, 12, and 17 days, respectively, consistent with previous published observations.⁴

Our findings indicate that HIV is readily transmitted by sexual intercourse during early PHI, and that the window of sexual infectiousness in PHI can begin as early as 7 days before the onset of the acute retroviral syndrome. Each case of PHI may thus present a unique public health opportunity to abort rapid epidemic spread in sexual networks.⁵ Both source patients and secondary cases of PHI can be identified by urgently tracing recent sexual contacts, and secondary transmission risk can be reduced for all infected patients by counseling along with antiretroviral therapy¹ and/or treatment for STDs.⁶