The mononuclear cells and plasma components of semen from HIV-infected subjects have been shown to contain HIV-1. However, there is very little information as to whether distinct HIV-1 population are present in these two seminal compartments or as to their tissue of origin. Phylogenetic analysis of nucleotide sequences of the C2-V5 region of the HIV-1 gp120 from HIV-1 RNA isolated from seminal cells and seminal plasma of five subjects indicates that the HIV-1 population derived from seminal plasma was distinct from that present in seminal cells. Such subcompartmentalization of HIV-1 between seminal cells and seminal plasma was detected as early as 3 months after seroconversion and persisted up to 38 months following seroconversion. Furthermore, comparison of HIV-1 sequences between testis and prostate tissues showed distinct HIV-1 populations in these tissue compartments. In situ real-time (Taqman) PCR analysis of prostate and testis tissues indicated that T lymphocytes were the predominant cells infected with HIV-1 in both of these tissues. Since seminal plasma is derived from prostate and most of the seminal cells originate from the rete testis and epididymis, these results are consistent with the idea that HIV-1 in seminal plasma is derived from the prostate, while HIV-1-infected cells in semen originate mostly from the rete testis and epididymis. These findings provide for the first time evidence of subcompartmentalization of HIV-1 in male genital organs and suggest that intervention strategies such as vasectomy may not prevent sexual transmission.

Clinical investigators are increasing their use of quantitative determinations of HIV viral load in their study populations. The distributions of these measures may be highly skewed, left-censored, and with an extra spike below the detection limit of the assay. We recommended use of a mixture model in this situation, with two sets of explanatory covariates. We extend this model to incorporate multiple measures across time, and to employ shared parameters as a way of increasing model efficiency and parsimony. Data from a cohort of HIV-infected men are used to illustrate these features, and simulations are performed to assess the utility of shared parameters.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• There is large interindividual variability in the pharmacokinetics of protease inhibitors (PIs) among human immunodeficiency virus (HIV)-infected individuals under highly active antiretroviral therapy. • Protease inhibitor have been recently reported to be substrates of the SLCO1B1/OATP1 drug transporter.• A single nucleotide polymorphism (SNP) in the SLCO1B1 gene (521T→C) was associated with plasma levels of lopinavir in HIV-infected individuals. WHAT THIS STUDY ADDS• Data on the impact of three SLCO1B1 SNPs (521T→C, 388A→G, 463C→A) on the trough plasma concentration of lopinavir and ritonavir in a cohort of 99 adult HIV-infected Brazilian men under stable highly active antiretroviral therapy.• Evidence that carriers of the 521C allele display significantly higher lopinavir, but not ritonavir plasma concentrations relative to the wild-type TT genotype.• No effect of either 388A→G or 463C→A SNPs on lopinavir or ritonavir plasma concentrations.• Further studies are required to confirm the clinical significance of the association between the SLCO1B1521T→C polymorphism and lopinavir pharmacokinetics. AIMSTo investigate possible associations between three SLCO1B1 single nucleotide polymorphisms (388A→G, 463C→A, 521T→C) and lopinavir/ritonavir plasma concentrations. METHODSThe study included 99 human immunodeficiency virus-infected men on stable highly active antiretroviral therapy containing lopinavir/ritonavir. Trough concentrations of lopinavir and ritonavir in plasma were quantified using liquid chromatography-tandem mass spectrometry. Genotyping of SLCO1B1388A→G, 463C→A and 521T→C polymorphisms was performed by allelic discrimination using real-time polymerase chain reaction. RESULTSThe trough concentration of lopinavir in plasma is significantly associated with SLCO1B1521T→C genotypes (P = 0.03). There is a significant trend for increasing concentrations of lopinavir from TT to TC to CC genotypes (P = 0.02). Carriers of the 521C allele display significantly higher lopinavir plasma concentrations relative to the wild-type TT genotype (P = 0.03). CONCLUSIONSReduced uptake of lopinavir by hepatocytes in carriers of the 521C allele may account for these results, but further studies to confirm the clinical importance of SLCO1B1 polymorphisms in lopinavir pharmacokinetics are warranted.British Journal of Clinical Pharmacology DOI:10.1111DOI:10. /j.1365DOI:10. -2125DOI:10. .2009 Br J Clin Pharmacol / 69:1 / 95-98 / 95