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Effects of steady-state rifabutin on the pharmacokinetics of steady-state maraviroc were investigated in fourteen healthy adult female and male volunteers. Maraviroc 300 mg twice daily (BID) was given orally with food for fifteen days. On day six, rifabutin 300 mg once daily (QD, P.O.) was added to the regimen. Formal pharmacokinetic (PK) sampling was performed on days five and fifteen. Individual plasma drug concentration-time data for maraviroc, and rifabutin on day fifteen, were obtained using validated High Performance Liquid Chromatography (HPLC) tandem Mass Spectrometry (MS/MS). Rifabutin steady state exposure was comparable to data in the literature. Maraviroc area under the curve (AUC) and minimum plasma concentration (Clast or Cmin) were reduced by 17% and 30% respectively when co-administered with rifabutin. No unexpected or serious adverse eventsoccurred. Based on the reduced exposure of maraviroc observed in this study, increasing the dose of maraviroc may be studied to normalize its moderately reduced exposure following rifabutin co-administration, a moderate inducer of CYP3A4.

Summary In this study, we investigated the role and expression of T helper type 17 (Th17) cells and Th17 cytokines in human tuberculosis. We show that the basal proportion of interferon (IFN)-γ-, interleukin (IL)-17- and IL-22-expressing CD4+ T cells and IL-22-expressing granulocytes in peripheral blood were significantly lower in latently infected healthy individuals and active tuberculosis patients compared to healthy controls. In contrast, CD4+ T cells expressing IL-17, IL-22 and IFN-γ were increased significantly following mycobacterial antigens stimulation in both latent and actively infected patients. Interestingly, proinflammatory IFN-γ and tumour necrosis factor (TNF)-α were increased following antigen stimulation in latent infection. Similarly, IL-1β, IL-4, IL-8, IL-22 and TNF-α were increased in the serum of latently infected individuals, whereas IL-6 and TNF-α were increased significantly in actively infected patients. Overall, we observed differential induction of IL-17-, IL-22- and IFN-γ-expressing CD4+ T cells, IL-22-expressing granulocytes and proinflammatory cytokines in circulation and following antigenic stimulation in latent and active tuberculosis.

Previously it has been shown that tipranavir-ritonavir (TPV/r) does not affect efavirenz (EFV) plasma concentrations. This study investigates the effect of steady-state EFV on steady-state TPV/r pharmacokinetics. This was a single-center, open-label, multiple-dose study of healthy adult female and male volunteers. TPV/r 500/200 mg twice a day (BID) was given with food for 24 days. After dosing with TPV/r for 10 days, EFV 600 mg once a day was added to the regimen. Intensive pharmacokinetic (PK) sampling was done on days 10 and 24. Validated bioanalytical high-pressure liquid chromatography-tandem mass spectrometry methods were used to determine plasma tipranavir (TPV), ritonavir (RTV), and EFV concentrations. Thirty-four subjects were entered into the study, and 16 subjects completed it. The geometric mean ratios (90% confidence intervals) for TPV and RTV area under the curves,Cmaxs, andCmins comparing TPV/r alone and in combination with EFV were 0.97 (0.87 to 1.09), 0.92 (0.81 to 1.03), and 1.19 (0.93 to 1.54) for TPV and 1.03 (0.78 to 1.38), 0.92 (0.65 to 1.30), and 1.04 (0.72 to 1.48) for RTV. Frequently observed adverse events were diarrhea, headache, dizziness, abnormal dreams, and rash. EFV had no effect on the steady-state PK of TPV or RTV, with the exception of a 19% increase in the TPVCmin, which is not clinically relevant. TPV/r can be safely coadministered with EFV and without the need for a dose adjustment.

This genotype panel study investigated the effect of ABCB1 polymorphism in exon 26 (C3435T), exon 21 (G2677T/A), and exon 12 (C1236T) on saquinavir pharmacokinetics and on the expression and activity of P-glycoprotein (P-gp) in peripheral blood monocytic cells (PBMCs). One hundred and fifty healthy volunteers were genotyped to identify 15 TT3435 and 15 CC3435 individuals. In these individuals, saquinavir pharmacokinetics were assessed after administration of a single oral dose of saquinavir 1,000 mg and saquinavir/ritonavir 1,000/100 mg. PBMC P-gp expression and activity were assessed in 15 and 19 subjects. The co-administration of ritonavir on study day 2 caused a significant increase in saquinavir exposure, in both TT3435 and CC3435 individuals. No correlation was observed between the ABCB1 C3435T, G2677T/A, and C1236T polymorphisms, separately and in haplotypes, with saquinavir pharmacokinetics, administered with or without ritonavir and with PBMC P-gp expression and activity. In conclusion, ABCB1 polymorphism has no pronounced effect on saquinavir exposure. Clinical Pharmacology & Therapeutics (2007) 82, 389–395; doi:10.1038/sj.clpt.6100157; published online 14 March 2007

The purpose of this study was to evaluate a novel psycho-educational intervention intended to increase patients' medication preparedness and treatment adherence skills before initiating highly active antiretroviral therapy (HAART). Sixty-three HIV-positive patients not currently on antiretroviral therapy participated in a randomized controlled trial of a standardized, four-session psycho-educational intervention (Supportive Therapy for Adherence to Antiretroviral Treatment; STAART). Session topics included learning techniques to increase medication adherence and learning effective strategies to cope with stress and depression. Patients completed psychological questionnaires assessing psychological readiness to initiate HAART and depressed mood. They completed both measures at study baseline and at four-weeks post-baseline. After controlling for baseline medication readiness scores, intervention patients (n = 30) reported significantly higher mean medication readiness following the STAART intervention (four-weeks post-baseline) (27.3+/-6.9) compared to controls (n = 33; 24.6+/-9.9; p0.05). Among depressed patients (n = 27), those receiving the intervention (n = 15) reported significantly lower mean depression scores at four-weeks post-baseline (22.5+/-12.9) compared to controls (n = 12; 27+/-9.9; p0.05). The STAART intervention enhanced HIV treatment readiness by better preparing patients prior to initiating HAART. It was also beneficial for reducing depressive symptoms in depressed, HIV-positive patients.

Aims To compare the pharmacokinetics of lopinavir/ritonavir (LPV/r) 800/200 mg administered once daily in the morning compared with the evening. Methods This was a randomized, two-way, cross-over study in HIV+ subjects. In each subject the pharmacokinetics of each drug were characterized after 2 weeks of LPV/r 800/200 mg administered once daily at 08.00 h and 19.00 h. On study days, LPV/r was taken with a standardized meal (800 kCal, 25% from fat) after fasting for at least 5 h. LPV/r concentrations were measured by LC-MS/MS, and the data were analyzed by noncompartmental pharmacokinetic analysis. Results Fourteen subjects completed the study (all men, mean age/weight 44 year/81 kg). The median (interquartile range) LPV AUC(0,24 h), maximum plasma concentration (Cmax) and concentration at the end of the dosing interval (C24 h) after am and pm dosing was, respectively, 143 (116–214) mg l−1 h, 12.8 (10.3–17.2) mg l−1, 1.34 (0.58–3.25) mg l−1, and 171 (120–232) mg l−1 h, 12.9 (8.22–16.3) mg l−1, 1.15 (0.59–1.98) mg l−1. The geometric mean ratio (GMR, am : pm) and 95% CI of the LPV AUC(0,24 h), Cmax, and C24 h was 0.91 (0.79, 1.06), 1.11 (0.94, 1.32), and 1.19 (0.72, 1.96), respectively. The median ritonavir Cmax after am and pm dosing was 1.05 and 0.90 mg l−1, respectively. The GMR (95% CI) of the RTV AUC(0,24 h), Cmax, and C24 h was 0.93 (0.80, 1.08), 1.27 (1.00, 1.63), and 1.04 (0.68, 1.60), respectively. Administration of LPV/r in a once-daily regimen was generally well tolerated. Conclusions No differences were observed in the pharmacokinetics of LPV/r after am or pm dosing with food, which suggests that this once daily combination, can be taken in the morning or evening. Such flexibility in dosing may improve adherence.

CPG 7909, a 24-mer B-Class CpG oligodeoxynucleotide (ODN), was tested for safety, tolerability and its ability to augment the immunogenicity of a commercial trivalent killed split influenza vaccine (Fluarix containing A/Beijing/262/95, A/Sydney/5/97 and B/Harbin/7/94; SmithKline Beecham) in a phase Ib blinded, randomized, controlled clinical trial. Sixty healthy volunteers were recruited in two consecutive cohorts of 30 subjects, who were randomly assigned to receive Fluarix plus 1mg CPG 7909 or Fluarix plus saline control (15 subjects each). Vaccines were administered by intramuscular injection on a single occasion with subjects in the first cohort receiving a 1/10th dose of Fluarix and those in the second cohort receiving the full-dose. All safety measures including physical evaluation, laboratory blood assays, and assays for DNA autoimmunity were within normal values except for transient and clinically inconsequential decreases in total white blood cell counts in groups receiving CPG 7909. All vaccines were found to be generally well tolerated with similar frequency and intensity for most adverse reactions for groups receiving CPG 7909 as controls. Exceptions were injection site pain and headache, which were reduced in frequency in subjects receiving the 1/10th Fluarix dose without CpG, compared to the frequency in all other groups. There was a lack of pre-existing immunity, defined as hemagglutinin inhibition (HI) activityor =20, for all subjects to the influenza strains A/Beijing/262/95 and B/Harbin/7/94 and for some subjects to A/Sydney/5/97. Post-vaccination humoral immune responses, as determined 2 and 4 weeks later by assay of HI activity and ELISA to detect antibodies against hemagglutinin (anti-HA) were similar for both full and reduced Fluarix doses but the cellular immune responses (measured as PBMC antigen-specific IFN-gamma secretion) were reduced in the 1/10th Fluarix dose group. Humoral responses were not significantly enhanced by the addition of CPG 7909, except in individuals with pre-existing immunity to A/Sydney/5/97 strain (baseline HI activity titre20), where there was a trend to higher HI activity with CPG 7909 (P = 0.06). The addition of CPG 7909 to the 1/10th dose of Fluarix did however result in significantly higher levels of IFN-gamma secretion from peripheral blood mononuclear cells recovered at 4 weeks and restimulated ex vivo with A/Beijing/262/95 (P = 0.048) and B/Harbin/7/94 (P = 0.0057), restoring these to the level seen with full-dose vaccine. These results suggest that addition of CPG 7909 to Fluarix may allow the use of reduced vaccine doses without reduced immunogenicity.

Background Many studies have explored the role of "classic" sexually transmitted diseases (STDs) in determining the pattern of HIV epidemics. However, the many different STDs may contribute in different ways, at different magnitudes. Goal To review available studies on the bidirectional interactions of HIV and STDs to explore the extent of current knowledge on the different influences of the varied STDs in heterosexual HIV epidemics. Methods Longitudinal studies on susceptibility and controlled studies on infectiousness and duration of disease identified on electronic databases through reference lists and citation indices up to the end of 1999 were systematically reviewed, including meta-analyses assessing the influence of STDs on susceptibility to HIV. Results Studies have a clear publication bias with a significant result that hinders robust interpretation. However, genital ulcerative disease appears to have a greater impact than nonulcerative disease, and men are more affected than women by the effects of STDs on susceptibility to HIV. There is evidence that STDs increase the infectiousness of HIV from men to women, whereas the evidence is more equivocal for the infectiousness of women. Few studies identify the impact of different STDs, and there is a marked lack of studies investigating the impact of HIV infection on the transmission of other STDs. Conclusions A large body of work has measured the association between STDs and HIV. However, publication bias and gaps in the focus of studies mean that a detailed, quantitative understanding of the interaction requires much more attention.

SUMMARY T helper (Th) responses are mediated in part by immunoregulatory cytokines and the signals delivered by the costimulatory CD28–B7 pathway. In this study, we have investigated the relationship between the regulation of B7 isoform expression on antigen-presenting cells from HIV+ individuals and the production of Th cytokines. The level of expression of both B7.1 and B7.2 isoforms as measured by mean channel fluorescence was significantly decreased on freshly isolated monocytes from HIV+ individuals compared with HIV− controls. However, the levels of expression of B7.1 and B7.2 on both B cells and monocytes increased significantly following culture in HIV+ individuals compared with HIV− controls. B7 expression is subject to regulation by immunoregulatory cytokines. Therefore, we analysed the regulation of B7 expression by cytokines, namely IL-10 and tumour necrosis factor-alpha (TNF-α), the production of which is enhanced in HIV infection and have similar inhibitory effects on B7 expression. Two groups of HIV+ individuals were distinguished on the basis of the inhibitory effect of IL-10 and TNF-α on monocyte B7.2 expression. IL-10 inhibited B7.2 expression on monocytes from some HIV+ individuals (termed responders) like the HIV− controls. However, in a subset of HIV+ individuals (non-responders) this inhibitory effect was lost. Loss of inhibition of B7.2 expression by IL-10 was associated with significantly reduced IL-2 production by phytohaemagglutinin (PHA)- stimulated peripheral blood mononuclear cells (PBMC). These observations showing an association of B7 dysregulation on monocytes and B cells with altered production of IL-2 may have implications in HIV immunopathogenesis.

BACKGROUND Dramatic reductions in plasma HIV RNA levels are possible with current antiretroviral regimens; the effect of potent therapies and "undetectable" viral load on the perceived risk of HIV transmission and need for safer practices remains unknown. METHODS A questionnaire was developed to examine perceptions of HIV transmission risk and need for safer practices with unprotected anal, vaginal, and oral sex and intravenous drug use with needle sharing for HIV-discordant couples in which the HIV-infected partner was receiving no therapy, was receiving reverse transcriptase inhibitor therapy, and protease inhibitor (PI)-based therapy with viral load "undetectable". This was applied anonymously to 147 unselected HIV-infected individuals attending a university-based HIV clinic. RESULTS Almost all respondents believed that all sexual activities except oral sex were "very risky" and that safer practices were "extremely important" for those not receiving antiretroviral agents. Significantly fewer considered that anal or vaginal sex was "very risky" for those receiving PI therapy (90.9% and 86.0%, respectively), and fewer thought that safer practices for anal or vaginal sex were "very important" for those receiving PI therapy (93.0% and 91.6%, respectively). In total, 20.4% thought the risk of HIV transmission for at least one activity was reduced for those receiving PI therapy, and 19.0% believed that the need for safer practices was reduced by PI therapy. CONCLUSION A small but significant proportion of HIV-infected people perceive the need for safer practices to be reduced during antiretroviral therapy, particularly those containing PIs. Even if the risk is truly reduced, the importance of safer practices should be conveyed consistently and terms such as "undetectable" to describe HIV RNA responses should be avoided.

Disseminated Mycobacterium avium complex (MAC) infection is common in persons with advanced HIV infection and can be prevented by prophylactic use of rifabutin; however, routine prophylaxis is costly and incompletely effective. Chronic anemia is a common manifestation of MAC infection. We conducted a retrospective population study of the annual incidence of MAC bacteremia and blood transfusion for anemia in a regional HIV-positive population before and after the introduction of rifabutin to determine the effect of MAC prophylaxis on the incidence of transfusion-requiring anemia. The HIV-infected patient populations in 1992 and 1993 were comparable in number, severity of immunodeficiency, and zidovudine (ZDV) use. The use of rifabutin for MAC prophylaxis for those with CD4 T-lymphocyte counts < 100/microl increased from 17.2% in 1992 to 33.7% in 1993 (p < 0.001), whereas diagnostic surveillance for MAC bacteremia was stable. In 1993, there was a decrease in the number of HIV-infected persons from whom MAC was isolated (10 vs. 26, p = 0.004), and a significant decrease in the number of patients transfused for anemia (15 vs. 35, p = 0.002), number of transfusion episodes, and numbers of units transfused, associated with significant cost and resource savings. Adoption of MAC prophylaxis was followed by a significant decrease in the number of diagnosed MAC infections and in transfusion requirements in an HIV-positive population with sustained surveillance and similar levels of immunodeficiency, which may represent a health and economic benefit of effective [correction of defective] MAC prophylaxis in a population at risk.

To study the mechanisms of inducible immunity to Haemophilus ducreyi infection in the temperature-dependent rabbit model of chancroid, we conducted passive immunization experiments and characterized the inflammatory infiltrate of chancroidal lesions. Polyclonal immunoglobulin G was purified from immune sera raised against H. ducreyi 35000 whole-cell lysate or a pilus preparation and from naive control rabbits. Rabbits were passively immunized with 24 or 48 mg of purified polyclonal immunoglobulin G intravenously, followed 24 h after infusion by homologous titered infectious challenge. Despite titratable antibody, no significant difference in infection or disease was observed. We then evaluated the immunohistology of lesions produced by homologous-strain challenge in sham-immunized rabbits and those protectively vaccinated by pilus preparation immunization. Immunohistochemical stains for CD5 and CD4 T-lymphocyte markers were performed on lesion sections 4, 10, 15, and 21 days from infection. Lesions of pilus preparation vaccinees compared with those of controls had earlier infiltration with significantly more T lymphocytes (CD5+) and with a greater proportion of CD4+ T lymphocytes at day 4 (33% +/- 55% versus 9.7% +/- 2%; P = 0.002), corroborating earlier sterilization (5.0 +/- 2 versus 13.7 +/- 0.71 days; P < 0.001) and lesion resolution. Intraepithelial challenge of pilus-vaccinated rabbits with 100 micrograms of the pilus preparation alone produced indurated lesions within 48 h with lymphoid and plasmacytoid infiltration, edema, and extravasation of erythrocytes. We conclude that passive immunization may not confer a vaccine effect in this model and that active vaccination with a pilus preparation induces a delayed-type hypersensitivity skin test response and confers protection through cell-mediated immunity seen as an amplified lymphocytic infiltrate and accelerated maturation of the T-lymphocyte response.

Using the temperature-dependent rabbit model of Haemophilus ducreyi infection as a quantitative virulence assay, we tested the abilities of two bacterial antigen preparations to induce protection against subsequent infection and disease. Lipooligosaccharide (LOS) and a pilus preparation were purified from H. ducreyi 35000 and were used in a booster immunization procedure. The serologic response to each immunogen was monitored by enzyme immunoassay. H. ducreyi virulence was assayed by intraepithelial inoculation and subsequent measurement of disease for homologous strain 35000 or clinical isolate RO-34. LOS and the pilus preparation induced humoral responses. The kinetics of the LOS antibody response suggest a type 1 T-independent response, whereas the pilus preparation induced an anamnestic response. An inoculum of 10(5) CFU of H. ducreyi 35000 or RO-34 consistently produced ulcerative chancroidal lesions in naive rabbit controls. Immunization with LOS did not modify the virulence of H. ducreyi 35000. Immunization with the strain 35000 pilus preparation significantly reduced the severity of disease and the duration of infection and disease compared with controls, with either homologous or heterologous strain infection. The histology of lesions from pilus preparation-vaccinated rabbits compared with that of lesions from controls revealed accelerated lymphoid cell recruitment, more prominent plasma cell infiltrate, and reduction in subsequent histiocytic infiltration. We conclude that both LOS and the pilus preparation are immunogenic and that the latter induces homologous and heterologous strain protection in this animal model of infection and disease.

To determine whether there is a simple relationship between body weight or body surface area (BSA) and serum zidovudine pharmacokinetic parameters in patients receiving oral zidovudine.Single-dose, pharmacokinetic study.Fifty-three asymptomatic and symptomatic HIV-infected men (CD4+ cell count500 x 10(6)/l) participated in the study. Results of renal function and haematology tests were within normal limits and all hepatic function tests were up to three times the upper limit of normal. Patients received 200 mg oral zidovudine and serial blood samples were collected for 4 h (18 patients) or 8 h (35 patients). Serum zidovudine concentrations were measured by high-performance liquid chromatography (12 patients) or radioimmunoassay (41 patients). Pharmacokinetic parameters were calculated by non-compartmental methods. The relationships between body weight or BSA and maximum serum concentration (Cmax), area under the concentration-time curve (AUC), apparent serum clearance (CL/F), and apparent terminal volume of distribution (Vz/F) were determined by simple least-squares linear regression.There were no significant relationships between either body weight or BSA and Cmax, AUC, Vz/F (corrected for weight), and clearance (P0.07; R20.06 for all comparisons). A significant positive association between Vz/F, uncorrected for weight, and either weight (P = 0.011; R2 = 0.121) or BSA (P = 0.022; R2 = 0.098) was observed. The interindividual coefficients of variation of CL/F and Vz/F values were only marginally reduced when the parameters were corrected for weight (31.3 versus 30.8% and 28.0 versus 26.0% respectively).There is little or no linear association between either body weight or BSA and observed serum zidovudine concentrations following administration of 200 mg zidovudine in adult male patients who are within 20% of their ideal weight.

The effect of a therapeutic dose of fluconazole on the disposition of zidovudine was evaluated in 12 men infected with human immunodeficiency virus. The study was designed as a randomized, two-period, two-treatment, crossover trial. On two occasions, 21 days apart, patients received either zidovudine alone or zidovudine (each, 200 mg every 8 h) and fluconazole (400 mg daily) for 7 days. Fluconazole coadministration decreased (P < .001) the apparent oral serum clearance of zidovudine by 43% and the apparent oral formation clearance to zidovudine glucuronide (GZDV) by 48%, resulting in increases (P < .002) in the area under the serum concentration time curve (74%), the maximum serum concentration (84%), and the terminal half-life (128%) of zidovudine. The molar ratio of GZDV to zidovudine recovered in urine was reduced by 34% with fluconazole (P < .001). These pharmacokinetic changes suggest that 400 mg of fluconazole inhibited the conversion of zidovudine to GZDV. Patients receiving this combination should be monitored for the development of zidovudine-related adverse reactions.

Populations of the Chalcolithic Levant as defined by archaeological excavations has in many cases reinforced the traditional scheme that a number of “races” are present. This scheme is usually based not only on differential cultural traditions as identified by archeologists, but also on the available skeletal evidence as discussed by physical anthropologists. Recently this view has been challenged and it has been suggested that the metrical and anatomical range of variability as identified within Chalcolithic populations can be subsumed into a single population or “racial” range. This paper examines both the available biological and archaeological evidence from the Chalcolithic Levant and concludes that there is no strong archaeological or biological evidence to support a multiple “racial” origin for the Chalcolithic of the Levant.

Research has revealed differences on scales measuring HIV knowledge between individuals from various ethnic backgrounds and cultures. Few studies have examined this knowledge with immigrant populations and persons living with HIV. This study examined HIV knowledge among persons living with HIV who were either born in Canada or in sub-Saharan Africa and, for comparison, in a sample of college students. All participants were residing in Canada. Participants completed questionnaires measuring demographic variables, sexual health behaviour, and HIV status, treatment, and knowledge. Canadian-born patients living with HIV were more likely to be older and male than the other groups. On average, patients living with HIV were diagnosed 6.4 years ago, and 80% reported having current or previous experience taking HIV medications. After adjusting for age and gender, significant differences were found between the groups on the Brief HIV Knowledge Questionnaire. Canadian-born persons living with HIV (n = 110) scored higher than sub-Saharan African-born patients (n = 23) and college students (n = 81); mean percentage correct was 86, 70, and 62%, respectively (P < .01). These results suggested that ongoing HIV education is needed for all groups, and that additional tailored and targeted educational interventions are needed to address important gaps in knowledge among persons living with HIV patients originating from Africa and among college students.

The ability to measure accurately viral RNA in the plasma (1-3) and intracellular (4-7) compartments of HIV-1-infected persons has led to a dramatic improvement in our understanding of the natural history of HIV-1/AIDS. A number of recent studies have convincingly demonstrated that high levels of viral replication occur at all stages of disease (8-10), and that changes in viral RNA load are predictive of disease outcome (11,12) and response to therapy (13,14). These findings, combined with the introduction of potent new antivirals (15,16), have stimulated a growing interest in viral load monitoring, both as a function of disease status, and as a predictor of disease progression and therapeutic efficacy.

The non-steroidal androgen-receptor antagonists WS9761 A (1,6,10-trihydroxy-2,8,10-trimethylanthrone) and WS9761 B (1,6,10-trihydroxy-2-hydroxymethyl-8,10-dimethylanthrone) were synthesized for the first time in racemic form by using Diels-Alder methodology followed by regioselective Grignard addition.

To identify pharmacokinetic (PK) drug-drug interactions between tipranavir-ritonavir (TPV/r) and rosuvastatin and atorvastatin, we conducted two prospective, open-label, single-arm, two-period studies. The geometric mean (GM) ratio was 1.37 (90% confidence interval [CI], 1.15 to 1.62) for the area under the concentration-time curve (AUC) for rosuvastatin and 2.23 (90% CI, 1.83 to 2.72) for the maximum concentration of drug in serum ( C max ) for rosuvastatin with TPV/r at steady state versus alone. The GM ratio was 9.36 (90% CI, 8.02 to 10.94) for the AUC of atorvastatin and 8.61 (90% CI, 7.25 to 10.21) for the C max of atorvastatin with TPV/r at steady state versus alone. Tipranavir PK parameters were not affected by single-dose rosuvastatin or atorvastatin. Mild gastrointestinal intolerance, headache, and mild reversible liver enzyme elevations (grade 1 and 2) were the most commonly reported adverse drug reactions. Based on these interactions, we recommend low initial doses of rosuvastatin (5 mg) and atorvastatin (10 mg), with careful clinical monitoring of rosuvastatin- or atorvastatin-related adverse events when combined with TPV/r.

BACKGROUND Human immunodeficiency virus (HIV)-infected persons are hyporesponsive to hepatitis B virus (HBV) vaccination. CPG 7909 is an oligodeoxynucleotide containing immunostimulatory CpG motifs that activate human B and plasmacytoid dendritic cells via Toll-like receptor 9. We previously reported that addition of CPG 7909 to a commercial HBV vaccine enhanced the kinetics, magnitude, and longevity of the seroprotective response over 48 weeks. We now report data for the 5-year period following vaccination. METHODS A randomized, double-blind, controlled trial was conducted to determine clinical safety and immunogenicity of HBV vaccine in adult HIV-infected subjects receiving effective antiretroviral therapy. HBV-susceptible subjects, one-half of whom had experienced previous vaccination failure, were vaccinated at 0, 1, and 2 months with a double adult dose of recombinant HBV vaccine, with or without 1 mg of CPG 7909 (19 subjects per arm). Titers of antibody to HBV surface antigen (anti-HBs) were measured at 6-month intervals for up to 60 months. RESULTS The proportion of participants achieving and retaining seroprotection (surface antibody titers, > or =10 mIU/mL) was greater in CPG 7909 recipients (P < .05 at all time points). Geometric mean anti-HBs titers were higher in the CPG 7909 group than in the control group (without CPG 7909 adjuvant) at all measured time points. CONCLUSIONS The immunostimulatory properties of CPG 7909 present an important strategy in achieving long-term protection in HIV-infected patients and other HBV vaccine-hyporesponsive populations.

Accurate treatment knowledge is required for patients to successfully manage complex medical conditions. Existing HIV knowledge scales focus on disease transmission and risk factors. This is the first study to develop and validate a scale to measure HIV treatment knowledge about complex treatment issues such as adherence, side-effects and drug resistance. A total of 346 participants were recruited into this cross-sectional study. Participants included HIV-positive patients (n=130), HIV-hepatitis C co-infected patients (n=22), hepatitis C patients, (n=78), community healthcare providers (n=35) and college students (n=81). Participants completed the proposed HIV Treatment Knowledge Scale and a validated measure of general knowledge about HIV transmission and risk factors. Two-week test-retest data were collected. Results demonstrated that the HIV Treatment Knowledge Scale was significantly correlated with general HIV knowledge across all samples. Among HIV-positive patients, the HIV Treatment Knowledge Scale was positively associated with time since HIV diagnosis. HAART-experienced patients had significantly higher treatment knowledge than HAART-naive patients. HIV-positive patients scored significantly higher than hepatitis C patients and college students on HIV treatment knowledge. Test-retest reliability (r=0.83) and internal consistency (reliability coefficient=0.90) were both satisfactory. The HIV Treatment Knowledge Scale is a novel, easy-to-administer measure demonstrating high levels of validity and reliability. It has important applications as a clinical teaching tool with patients and healthcare workers and it could be used as an outcome indicator in HIV educational intervention studies.

Increases in the rates of sexually transmitted infections (STIs) suggest that control programmes may not be effectively targeting diverse subpopulations. The objective of this investigation was to examine STI transmission within different groups, using both social network analysis and cluster analysis. Routine partner notification data were analysed from individuals diagnosed with, or exposed to an STI in Manitoba. Groups were identified and characterized. Three different clusters of groups were identified, comprised of demographically and clinically distinct individuals. A greater understanding of disease transmission patterns within these groups will aid in the development of targeted education and prevention programmes for all STIs.

This clinical trial aims to evaluate if natural mixed carotenoids supplementation can improve the health and survival of acquired immunodeficiency syndrome (AIDS) patients.A placebo-controlled, prospective, randomized, double-blind, multicenter clinical trial.Community, tertiary care human immunodeficiency virus (HIV) clinics of the Canadian HIV Trials Network (CTN).Three hundred and thirty-one adults with advanced AIDS on conventional management were recruited during routine clinic visits.All participants, including 166 controls, received daily oral specially formulated multivitamins including vitamin A and trace elements; 165 treatment group participants received additional daily oral natural mixed carotenoids, equivalent to 120,000 IU (72 mg) of beta-carotene daily. Follow-up was quarterly at routine clinic visits.Mean (s.d.) follow-up was for 13 (6) months. Thirty-six participants died by 18 months. Serum carotene concentration1.0 micromol/l was present in 16% participants at baseline. Despite variation in carotene content of the treatment medication, serum carotene concentrations increased significantly to twice the baseline levels to 18 months follow-up in participants who received carotenoids treatment compared with controls (P0.0001). Although not statistically significant, mortality was increased in participants who did not receive carotenoids treatment compared with those who did (HR time to death 1.76, 95% CI 0.89, 3.47, P = 0.11). In multivariate analysis, survival was significantly and independently improved in those with higher baseline serum carotene concentrations (P = 0.04) or higher baseline CD4 T-lymphocyte counts (P = 0.005). Adjusted mortality was also significantly and independently increased in those who did not receive carotenoids treatment compared with those who did (HR time to death 3.15, 95% CI 1.10, 8.98, P = 0.03).Low serum carotene concentration is common in AIDS patients and predicts death. Supplementation with micronutrients and natural mixed carotenoids may improve survival by correction of a micronutrient deficiency. Further studies are needed to corroborate findings and elucidate mechanism of action.

Edendale Hospital, Pietermaritzburg, KwaZulu Natal, South Africa, a 1275-bed hospital that serves a mainly ethnic African population of 1.6 million.To describe the demographic and clinical characteristics of hospitalised active tuberculosis (TB) cases, and correlates of their in-hospital survival.A retrospective cohort study of adult TB cases admitted to the medical wards, 16 November to 13 December 2001.Of 760 (28%) admissions, 215 had active TB, of whom 26.5% died in hospital. Patients were mostly young, first diagnosed on admission, and had pulmonary TB. Human immunodeficiency virus (HIV) co-infection was common and predicted by lower absolute lymphocyte count (OR 1.2, 95% CI 1.05-1.38). Extra-pulmonary TB, including pleural and pericardial, was significantly associated with not having HIV infection. In-hospital death was predicted by TB diagnosed prior to admission (OR 3.18, 95% CI 1.67-6.07), acquired immune-deficiency syndrome (AIDS) associated disease, and higher total leukocyte count--by higher leukocytes only in patients without AIDS (OR 8.52, 95% CI 2.67-27.13).Active TB was common in in-patients at an acute care hospital. TB patients presented late in disease and had high in-hospital mortality. Early detection and effective treatment of active TB in the community is likely to reduce hospitalisation and improve survival.

The numbers related to the HIV pandemic are staggering: 50 million infected since the emergence of the virus and 16,000 new infections daily. About 1 percent of the world's adult population is affected by the disease, and most of them will not have reasonable access to healthcare at any time in the foreseeable future. The author proposes that HIV could be controlled in some areas by treating commercial sex workers who are responsible for many new infections. This approach has been successful in treating other sexually transmitted diseases, such as syphilis and chancroid. Sex workers would be treated for all sexually transmitted diseases and educated about safer sex practices. Such a program could have a broad impact for a relatively small cost.

The regulation of telomere length may be involved in the cellular physiology of senescence, reproduction, cancer, immune response to infection, and possibly immune deficiency. The measurement of telomere length, critical to research in this area, has traditionally been performed by Southern blot analysis, which is cumbersome and time consuming. Several alternative methods have been described in recent years. Some, such as pulsed-field electrophoresis, slot blots, and centromere-to-telomere ratio measurements are essentially improvements to the Southern blot technique. However, other methods such as fluorescent in situ hybridization on metaphase chromosome spreads and flow cytometry-based fluorescent in situ hybridization represent a completely new technical approach to the problem. In this review, we compare methods, with particular emphasis placed on flow cytometric techniques for measuring telomere length in situ and identifying potential areas where improvements may still be made.

Antiretroviral treatment of patients infected with HIV results in improvements in CD4+ T cell number. Emerging evidence suggests that some of the improvements in CD4+ T cell number that occur in response to protease inhibitor (PI) therapy may not be accounted for solely by enhanced viral suppression, implying that PI may directly affect T cell survival. Since HIV T cell depletion is associated with enhanced apoptosis, we analyzed the effect of PIs on T cell apoptosis. In vitro treatment of peripheral blood lymphocytes (PBLs) from HIV-infected but untreated patients with reverse transcriptase inhibitors (RTIs) does not alter apoptosis, whereas PI treatment rapidly reduces CD4+ and CD8+ T cell apoptosis. In contrast, PI treatment does not alter apoptosis in PBL blasts from HIV-negative patients, or in Jurkat T cells. Consistent with this observation, 8 days of PI therapy in HIV-infected patients does not significantly alter plasma viremia, yet results in significant inhibition of CD4+ and CD8+ T cell apoptosis. The inhibitory effects of PI on apoptosis have implications concerning the treatment of HIV and its pathogenesis.

Objective: To evaluate the safety and antiretroviral activity of ritonavir (NorvirTM) and saquinavir (InviraseTM) combination therapy in patients with HIV infection. Design: A multicenter, randomized, open-label clinical trial. Setting: Seven HIV research units in the USA and Canada. Patients: A group of 141 adults with HIV infection, CD4 T lymphocyte counts of 100-500×106 cells/l, whether treated previously or not with reverse transcriptase inhibitor therapy, but without previous HIV protease inhibitor drug therapy. Interventions: After discontinuation of prior therapy for 2 weeks, group I patients were randomized to receive either combination (A) ritonavir 400mg and saquinavir 400mg twice daily or (B) ritonavir 600mg and saquinavir 400mg twice daily. After an initial safety assessment of group I patients, group II patients were randomized to receive either (C) ritonavir 400mg and saquinavir 400mg three times daily or (D) ritonavir 600mg and saquinavir 600mg twice daily. Investigators were allowed to add up to two reverse transcriptase inhibitors (including at least one with which the patient had not been previously treated) to a patient‚s regimen after week 12 for failure to achieve or maintain an HIV RNA level ≤ 200 copies/ml documented on two consecutive occasions. Measurements: Plasma HIV RNA levels and CD4+ T-lymphocyte counts were measured at baseline, every 2 weeks for 2 months, and monthly thereafter. Safety was assessed through the reporting of adverse events, physical examinations, and the monitoring of routine laboratory tests. Results: The 48 weeks of study treatment was completed by 75% (106/141) of the patients. Over 80% of the patients on treatment at week 48 had an HIV RNA level ≤200 copies/ml. In addition, intent-to-treat and on-treatment analyses revealed comparable results. Suppression of plasma HIV RNA levels was similar for all treatment arms (mean areas under the curve minus baseline through 48 weeks were -1.9, -2.0, -1.6, -1.8 log10 copies/ml in ritonavir-saquinavir 400-400mg twice daily, 600-400mg twice daily, 400-400mg three times daily, and 600-600mg twice daily, respectively). Median CD4 T-lymphocyte count rose by 128×106 cells/l from baseline, with an interquartile range (IQR) of 82-221×106 cells/l. The most common adverse events were diarrhea, circumoral paresthesia, asthenia, and nausea. Reversible elevation of serum transaminases (>5×upper limit of normal) occurred in 10% (14/141) of the patients enrolled in this study and was associated with baseline abnormalities in liver function tests, baseline hepatitis B surface antigen positivity, or hepatitis C antibody positivity (relative risk, 5.0; 95% confidence interval 1.5-16.9). Most moderate or severe elevations in liver function tests occurred in patients treated with ritonavir-saquinavir 600-600mg twice daily. Conclusions: Ritonavir 400mg combined with saquinavir 400mg twice daily with the selective addition of reverse transcriptase inhibitors was the best-tolerated regimen of four dose-ranging regimens and was equally as active as the higher dose combinations in HIV-positive patients without previous protease inhibitor treatment.

This paper examines patterns of sexual dimorphism within the Spanish hominid Hispanopithecus. The inclusion of this genus within the Hominidae suggests that extant male and female great ape sexually specific characters are appropriate features for determining the sex of these fossil hominids. It is shown that Hispanopithecus has a distinct sexually dimorphic pattern from that observed in the extant great apes. It is also demonstrated that H. laietanus and H. crusafonti each have a distinct sex pattern from each other. This result further supports the dual species hypothesis.

Ritonavir is a potent, orally bioavailable inhibitor of HIV-1 protease. We undertook an international, multicentre, randomised, double-blind, placebo-controlled trial of ritonavir in patients with HIV-1 infection and CD4-lymphocyte counts of 100 cells/microL or less, who had previously been treated with antiretroviral drugs.1090 patients were randomly assigned twice-daily liquid oral ritonavir 600 mg (n = 543) or placebo (n = 547) while continuing treatment with up to two licensed nucleoside agents. The primary study outcome was any first new, or specified recurrent, AIDS-defining event or death. Open-label ritonavir was provided after 16 weeks in the study to any patient who had an AIDS defining event.The baseline median CD4-lymphocyte count was 18 (IQR 10-43)/microL in the ritonavir group and 22 (10-47)/microL in the placebo group. Study medication was discontinued in 114 (21.1%) ritonavir-group patients and 45 (8.3%) placebo-group patients mainly because of initial adverse symptoms. Outcomes of AIDS-defining illness or death occurred in 119 (21.9%) ritonavir-group patients and 205 (37.5%) placebo-group patients (hazard ratio 0.53 [95% CI 0.42-0.66]; log-rank p0.0001) during median follow-up of 28.9 weeks, with loss to follow-up of 15 (1.4%) patients. Ritonavir was then offered to all patients; at median follow-up of 51 weeks, 87 (16%) ritonavir-group patients had died of any cause versus 126 (23%) placebo-group patients (hazard ratio 0.69 [95% CI 0.52-0.91], log-rank p = 0.0072).Although earlier intervention with combination therapy may provide much more effective treatment, ritonavir in patients with advanced disease and extensive previous antiretroviral use is safe and effective, lowers the risk of AIDS complications, and prolongs survival.

Acquired immunodeficiency syndrome (AIDS) has become a leading cause of death of young men in the United States. With the introduction of prophylaxes and antiretrovirals for opportunistic infection, there have been significant changes in the clinical history of human immunodeficiency virus (HIV) infection.To determine the cause of death of the patients followed up by our clinic from 1984 to 1995.A critical chart review was performed on the records of all patients affiliated with the Ottawa General Hospital HIV/AIDS Clinic, Ottawa, Ontario, who died between 1984 and July 15, 1995. Data regarding the cause of death, last CD4 T-lymphocyte cell count before death, medication use at time of death, and location and year of death were collected. Data were analyzed for 1984 through 1988, 1989 through 1991, and 1992 through 1995, corresponding to the evolution of HIV-related medical care.The median CD4 T-lymphocyte cell count at death had declined. Pneumocystis carinii pneumonia has decreased significantly as cause of death (28.6%-3.8%, P.001). No other specific attributable terminal illness has decreased in frequency during 11 years. The wasting illnesses, particularly HIV wasting syndrome (3.6%-13.7%, P = .04), and untreatable illnesses have increased in frequency as causes of death. Patients are increasingly likely to die at home (0%-25%, P.001) and less likely to die in hospital (54%-35%, P.001).The HIV-infected persons are dying with more advanced HIV immunosuppression. Advances in P carinii pneumonia prophylaxis and treatment have had a dramatic effect on the cause of death of HIV-infected persons. Improved prophylaxis and treatment for non-P carinii pneumonia opportunistic infections and malignancies and HIV wasting syndrome are required.

To the Editor: As a result of the recent problems in the production of influenza vaccine, there is concern about whether the demand for vaccine will outstrip the supply for the upcoming influenza season.1 An ample vaccine supply is an ever-present concern, given the potential for future influenza pandemics and avian influenza.2 We recently evaluated 1/10th-dose influenza vaccine (Fluarix) as part of a larger phase 1b, randomized, controlled, double-blind vaccine study.3 Healthy volunteers (age range, 18 to 40 years) with negative results on screening tests of hemagglutination inhibition (HAI) for A/Beijing/262/95 and B/Harbin/7/94 were enrolled after they had given written . . .

It has been suggested that didanosine (ddI) may undergo hepatic metabolism. Rifabutin is an inducer of drug metabolism. Fifteen human immunodeficiency virus-infected patients whose conditions were stabilized on twice-daily doses of ddI participated in a Phase I, open-label, pharmacokinetic and safety drug interaction study between rifabutin and ddI. Twelve patients completed the study. All patients received their regular ddI dose (167-375 mg) on day 1. On days 2-13 they received once-daily rifabutin (600 mg, three patients; 300 mg, nine patients) with their regular twice-daily ddI regimen. On days 14-16 they received rifabutin alone. Serial blood and urine samples were collected for 12 h on day 1 and for 24 h on days 13 and 16, and safety evaluations were made throughout the study. Average day 1/day 13 ddI pharmacokinetic ratios and 95% confidence interval values for Cmax, AUC0-infinity, Cls/F, and t 1/2, lambda z were 1.17 (0.96-1.38), 1.13 (0.99-1.27), 0.91 (0.81-1.01), and 0.97 (0.79-1.15), respectively (p0.05 for all comparisons; paired t test). A 20% difference in AUC0-infinity could be detected with 90% power. Also, there were no significant changes in laboratory values or electrocardiograms, or in rifabutin pharmacokinetic parameters when the two agents were coadministered. Based on the safety and pharmacokinetic assessments, rifabutin did not appear to interact with ddI.

The pharmacokinetics of zidovudine in 10 symptomatic HIV-infected men were assessed after administration of the initial 200 mg oral dose at the start of therapy (day 1) and on one occasion during non steady-state conditions of chronic-dose therapy (200 mg every 4 h while awake on day 21-66; 5 doses per day). The following mean (+/- s.d.) pharmacokinetic parameters were determined on day 1 and during chronic therapy, respectively: Cmax (4.09 +/- 2.54 vs 3.82 +/- 1.03 mumol l-1), oral clearance (40.7 +/- 12.9 vs 41.1 +/- 8.4 ml min-1 kg-1) and terminal half-life (68.4 +/- 29.4 vs 65.1 +/- 13.1 min). Mean pharmacokinetic parameters on day 1 were < 10% different (P > 0.34) from those determined during chronic therapy. Differences in means of 21% for clearance and 36% for Cmax could be detected with a power of 80% at the 5% significance level. Intra-subject coefficients of variation were 17% for clearance and 32% for Cmax, respectively. This study suggests that within a group of patients whose stage of HIV infection and general health are relatively stable, first-dose pharmacokinetic parameters provide a good estimate of multiple-dose pharmacokinetic parameters.

We standardized a serologic enzyme immunoassay (EIA) for human immunoglobulin G and M antibodies against Haemophilus ducreyi. We evaluated the performance of this test with respect to the time from acute chancroid and coinfection with human immunodeficiency virus (HIV). Antibody to a crude, soluble bacterial antigen of one H. ducreyi strain was detected in a panel of serum samples from clinically and microbiologically confirmed cases of chancroid and from controls. Test interpretation was standardized for optimal sensitivity and specificity. Performance of the EIA was enhanced in the period of early convalescence from acute primary chancroid and was not diminished in the presence of HIV coinfection. The EIA performed adequately as a serologic screening test for field evaluation and epidemiologic application in conjunction with sexually transmitted disease and HIV detection and control efforts.

The effect of continuous ambulatory peritoneal dialysis (CAPD) on zidovudine (ZDV) elimination was studied in two HIV-positive men. Serum and dialysate samples were collected after a single oral dose of 200 mg (patient 1) or 100 mg (patient 2) of ZDV, and again on at least one occasion during chronic therapy (100 mg every 8 h). Concentrations of ZDV and its glucuronide metabolite (GZDV) were measured by radioimmunoassay. ZDV serum half-lives on day 1 were 7.9 h (patient 1) and 2.6 h (patient 2). The apparent GZDV half-lives on day 1 were 19.9 h (patient 1) and 7.1 h (patient 2), with resultant accumulation of metabolite (up to 36 micrograms/ml) during chronic therapy. At 14 h following single dose, 8.2 +/- 0.4% of dose was recovered in dialysate as GZDV; ZDV accounted for less than 0.6% of dose recovered in dialysate after both single and multiple dose. After the initial dwell (tau) following single dose, peritoneal clearances of ZDV were 4.3 ml/min (tau = 4 h, patient 1) and 5.9 ml/min (tau = 5 h, patient 2), and GZDV clearances were 6.7 and 5.1 ml/min, respectively. ZDV serum protein binding was less than 10%. The small amount of unchanged ZDV removed by CAPD suggests that no supplemental doses are needed in HIV patients undergoing CAPD.

A community-based cohort of 595 prostitutes from Nairobi was enrolled to study the epidemiology of sexually transmitted diseases (STDs) during January-August 1985. Subgroups were followed at interval of 2 weeks to 1 month during April 1985-March 1987. Reassessments were made during September-December 1985 March-August 1986; and October 1986-June 1987. Of the 595 women 196 were initially HIV-1 antibody-negative. Of these 196 women all who seroconverted to HIV-1 (n = 83) and all who remained HIV-1-seronegative during at least 12 months of follow-up (n = 41) were included in this report. Serology for HIV-1 was done using an enzyme immunoassay (HTLV-III ELISA). Positive specimens were confirmed by HIV-1 Western blot (HTLV-III Western blot). Seroconversion to HIV-1 occurred in 83 women (67%) by the end of June 1987. Annual HIV-1 incidence was 47%. Of 85 women who never used oral contraceptives (OCs) 51 (60%) seroconverted compared with 16 (76%) of 21 who either stopped or started using OCs during the observation period and 16 (89%) of 18 who used OCs throughout the study period (p < 0.05). OC use was associated with HIV-1 infection. Of 39 reporting any OC use 32 seroconverted (odds ratio [OR] 3.1; 95% confidence interval [CI] 1.1-8.6; P m< 0.03). Genital ulcers (mean annual episodes 1.32 +or- 0.55 in seroconverting women vs. 0.48 +or- 0.21 in seronegative women (p < .02) were associated with increased risk of HIV-1 infection. Condom use reduced the risk of HIV-1 infection (OR 0.11; CI 0.05-0.27; p < .0001). Stepwise logistic regression analysis confirmed independent associations between HIV-1 infection and OC use condom use genital ulcers and C trachomatis. The presence of other STDs and genital ulcer disease linked to HIV-1 epidemiology may explain the heterosexual HIV-1 epidemic in Africa. If genital ulcers alter susceptibility to HIV-1 by producing mucosal disruption it seems plausible that other STDs that cause such disruption such as C trachomatis infection also facilitate HIV-1 transmission. This would call for the inclusion of STD control in AIDS control programs.

The authors studied the epidemiology of Chlamydia trachomatis infection in a trachoma-endemic area of central Kenya. Children with abnormal ocular discharge were evaluated for clinical evidence of trachoma and were cultured for C. trachomatis. Isolated strains of C. trachomatis were immunotyped with monoclonal antibodies. Overall, 221 children from 207 families were evaluated. Clinically, 91 children (41%) had trachomatous follicular inflammation, and 130 (59%) had papillary hypertrophy without visible follicle and were labeled as having mucopurulent conjunctivitis. C. trachomatis was isolated from 31 of 91 children with trachoma (34%) and 17 of 130 children with conjunctivitis (13%) (p less than 0.001). Twenty-two C. trachomatis strains were immunotyped: 17 were from children with trachoma (nine type A, one A/L2, five B, one Ba, and one E) and five were from children with conjunctivitis (two A, one Ba, one D, and one F). A total of 168 mothers were evaluated for cervical C. trachomatis infection, and seven (4%) were culture-positive. Two strains were immunotyped as serovar E. The authors conclude that C. trachomatis ocular infections are due to heterogeneous serovars in this area, that most cases of trachoma are due to C. trachomatis infection with the classic trachoma serovars (A, B, or Ba), and that cervical C. trachomatis infection is uncommon among mothers of children with trachoma.

Epidemiologic studies in Nairobi and elsewhere in Africa, have shown that men infected with HIV-1 more commonly have a history of genital ulcer disease compared to uninfected men. In one study, HIV infected men were three times as likely to have a recent history of genital ulcers. In a prospective study of seronegative men, those presenting with chancroid had a five-fold risk of seroconversion during follow-up compared to men presenting with urethritis. Uncircumcised men had an increased risk of seroconversion which was independent of their risk of genital ulcer disease. Over 95% of attributable risk in men with STD was either genital ulceration or the presence of a foreskin. Genital ulcers are a major risk factor for HIV infection among prostitutes. The increased risk is about 10-fold among prostitutes with ulcers compared to a cohort who did not. We hypothesize from these studies that genital ulcers are the major portals of entry for HIV infection and also increased shedding of virus infected cells into the vaginal secretions. HIV seropositive prostitutes are more susceptible to chancroid with a two-fold increase in the prevalence of genital ulcers as compared to HIV negative women. The use of condoms by their clients prevents both genital ulcer disease and HIV acquisition among prostitutes. Chancroid is more difficult to treat in HIV infected men with one-third of patients failing single dose treatment regimens as compared to less than five percent of men without HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

The structure of the title compound, (1α,4β,9aβ)-9a-chloro-1-methoxy-9,10-dioxo-3-trimethylsiloxy- 1,4,4a,9,-9a,10-hexahydro-4a-anthracenyl acetate, C 20 H 23 ClO 6 Si, was determined in order to ascertain the regiochemistry of the Diels-Alder reaction between acetoxychloronaphthoquinone and a 1,3-dioxybutadiene.