Thirty years after the first HIV case in French Guiana, the drivers of the epidemic are not clearly known, but the epidemic is usually conceptualized as generalized. Cross-linking results from a study in the general population and a study in the HIV-infected population in Cayenne suggests that in the general population of HIV-positive men, 45% of HIV cases are attributable to having sex with someone they paid. Similarly, for HIV-positive women exchanging sex for presents or money, 10.7% of HIV cases are attributable to transactional sex. A surprising finding was that 16.8% of HIV patients had tried crack cocaine before. On the Maroni river, the female-biased sex ratio suggests the drivers in that remote area may be related to cultural polygyny. These observations have important consequences on communication and prevention strategies.