Research Article: The effect of oral preexposure prophylaxis on the progression of HIV-1 seroconversion

Date Published: September 10, 2017

Publisher: Lippincott Williams & Wilkins

Author(s): Deborah Donnell, Eric Ramos, Connie Celum, Jared Baeten, Joan Dragavon, Jordan Tappero, Jairam R. Lingappa, Allan Ronald, Kenneth Fife, Robert W. Coombs.


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Multiple randomized clinical trials have shown that with good adherence, preexposure prophylaxis (PrEP), substantially reduces risk of HIV-1 acquisition [1–6]. This prevention strategy requires frequent high-quality HIV-1 testing among PrEP users to detect acute/early HIV-1 infection and minimize risk of resistance. Nonadherence to PrEP provides little HIV-1 protection but at the same time little risk of resistance if the patient is infected [7], whereas high adherence to PrEP blocks most transmissions [8]. For those who acquire HIV-1 in spite of PrEP – whether from sporadic adherence, or potentially a breakthrough with high adherence – it is unknown if PrEP use modifies the progression of seroconversion or the natural evolution of HIV-1 biomarkers.

There were a total of 138 HIV-1 seroconverters: 67 were assigned to PrEP during the seroconversion period (40 TDF, 27 FTC/TDF), and 71 received placebo. Fifteen were HIV-1 infected (HIV-1 RNA detected) but seronegative at initial randomization, 111 became infected on study, nine infections occurred during an off-study drug period and three were infected at placebo rerandomization. About half were men (46%), the median age was 30 and median viral load of their HIV-1-infected partners was more than 20 000 copies per/ml (Table 1). Among the 67 randomized to PrEP, 64 were assessed for TDF in plasma during the seroconversion period, and 31 (48%) had detectable TDF during that period, of whom15 had TDF concentrations more than 40 ng/ml, consistent with daily dosing [19,20].

In this analysis of a randomized, placebo controlled trial of PrEP, we showed that PrEP delayed the time to detect seroconversion for those participants who continued to take PrEP during acute/early clade C HIV-1 infection. Nonetheless, the majority of HIV-1 infections were detected within 3 months, which corresponds to the currently recommended HIV-1 testing frequency for patients on PrEP. We also observed a consistent trend of increased time for Fiebig stage progression among the seroconverters with TDF-monitored evidence of continued PrEP exposure. A statistically significant delay occurred only for Fiebig stage 5, likely because it has the longest duration and thus was observed most frequently. Although our analysis suggests PrEP may elongate seroconversion, the delay in detection was not associated with developing resistant virus, thus the clinical consequences on seroconversion appear unlikely to be significant.

D.D., C.C. and J.B. contributed to the design and execution of the study had full access to the data. D.D. conducted the statistical analyses and wrote the first draft of the article. E.R., J.D. and R.B. conducted the laboratory testing and contributed to the design of the study. J.T., J.R.L., A.R. and K.F. contributed to the design and execution of the study. All authors contributed to critical review and approved the final article.




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