RESISTANCE OF HIV-1 TO ANTIRETROVIRAL AGENTS IN BLOOD AND SEMINAL PLASMA - IMPLICATIONS FOR TRANSMISSION

Objectives: To evaluate blood and genital secretions from HIV-infected men for HIV-1 resistant to antiretroviral agents. Design: A longitudi nal study of 11 men with HIV infection and persistent detectable HIV R NA levels in blood and semen on antiretroviral therapy. Methods: HIV-1 from the blood and seminal plasma, obtained before the initiation of a new therapeutic regimen and on therapy, were evaluated by population -based sequencing of reverse transcriptase (RT) and protease RNA for t he development of resistance to antiretroviral therapy. The genetic re latedness of sequences over time was compared. Results: RT genotypic r esistance markers were present in seminal plasma at baseline in three out of six individuals with previous RT inhibitor experience. Eight ou t of 10 men: from whom the viral sequence was available on new therapy , demonstrated the evolution of new resistance mutations in the blood or seminal plasma, or both. The evolution of resistance mutations in b lood and semen were frequently discordant, although over time similar patterns were seen. in two individuals, protease inhibitor resistance mutations evolved in the blood but not in the major variant in seminal plasma. Comparisons of the viral sequences between blood and seminal plasma from six men revealed two patterns. Three men showed a clusteri ng of sequences from blood and semen. Three had sequences that appeare d to evolve separately in the two compartments. Conclusions: HIV-1 var iants with genotypic resistance markers are present in the male genita l tract and evolve over time on incompletely suppressive antiretrovira l therapy. The absence of genotypic changes consistent with protease i nhibitor resistance in the semen, despite their presence in blood plas ma, suggests the possibility of limited penetration of these agents in to the male genital tract. Sexual transmission of resistant variants m ay have a negative impact on treatment outcome in newly infected indiv iduals and on the spread of the diseases within a population. Therapeu tic strategies that fully suppress HIV-1 in the genital tract should b e a public health priority. (C) 1998 Lippincott Williams & Wilkins.