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1.
BMC Infect Dis ; 13: 256, 2013 Jun 03.
Article in English | MEDLINE | ID: mdl-23732043

ABSTRACT

BACKGROUND: Although some studies show higher antiretroviral concentrations in women compared to men, data are limited. We conducted a cross-sectional study of HIV-positive women to determine if protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) C(min) and Cmax values were significantly different than historical general population (predominantly male) averages and to evaluate correlates of higher concentrations. METHODS: HIV-positive women with virologic suppression (viral load < 50copies/mL) on their first antiretroviral regimen were enrolled. Timed blood samples for C(min) and Cmax were drawn weekly for 3 weeks. The ratio of each individual's median C(min) and Cmax to the published population mean values for their PI or NNRTI was calculated and assessed using Wilcoxon sign-rank. Intra- and inter-patient variability of antiretroviral drug levels was assessed using coefficient of variation and intra-class correlation. Linear regression was used to identify correlates of the square root-transformed C(min) and Cmax ratios. RESULTS: Data from 82 women were analyzed. Their median age was 41 years (IQR=36-48) and duration of antiretrovirals was 20 months (IQR=9-45). Median antiretroviral C(min) and Cmax ratios were 1.21 (IQR=0.72-1.89, p=0.003) (highest ratios for nevirapine and lopinavir) and 0.82 (IQR=0.59-1.14, p=0.004), respectively. Nevirapine and efavirenz showed the least and unboosted atazanavir showed the most intra- and inter-patient variability. Higher CD4+ count correlated with higher C(min). No significant correlates for Cmax were found. CONCLUSIONS: Compared to historical control data, C(min) in the women enrolled was significantly higher whereas Cmax was significantly lower. Antiretroviral C(min) ratios were highly variable within and between participants. There were no clinically relevant correlates of drug concentrations. TRIAL REGISTRATION: NCT00433979.


Subject(s)
Anti-Retroviral Agents/pharmacokinetics , HIV Infections/metabolism , Adult , Alkynes , Anti-Retroviral Agents/blood , Anti-Retroviral Agents/therapeutic use , Atazanavir Sulfate , Benzoxazines/blood , Benzoxazines/pharmacokinetics , Benzoxazines/therapeutic use , Cross-Sectional Studies , Cyclopropanes , Drug Therapy, Combination , Female , HIV Infections/blood , HIV Infections/drug therapy , Humans , Linear Models , Middle Aged , Nevirapine/blood , Nevirapine/pharmacokinetics , Nevirapine/therapeutic use , Oligopeptides/blood , Oligopeptides/pharmacokinetics , Oligopeptides/therapeutic use , Pyridines/blood , Pyridines/pharmacokinetics , Pyridines/therapeutic use , Risk Factors , Viral Load
2.
Antivir Ther ; 13(1): 87-95, 2008.
Article in English | MEDLINE | ID: mdl-18389902

ABSTRACT

BACKGROUND: There is a lack of standardized programs for HIV counselling and post-exposure prophylaxis (PEP) in the setting of sexual assault. METHODS: We conducted an 18-month prospective cohort study assessing universal HIV counselling for all sexual assault survivors presenting to 18 Ontario Sexual Assault Treatment Centres. HIV PEP was universally offered to those at risk of HIV infection (high risk or unknown risk) presenting < or =72 h after the assault, using Combivir one pill and Kaletra three capsules twice a day for 28 days. Those who accepted HIV PEP were monitored via a schedule of frequent follow ups. The primary outcomes were acceptance and completion rates, and their predictors were determined using multivariable logistic regression. Adverse events (AE) were categorized using a standardized toxicity grading system. RESULTS: Of the 900 evaluable participants eligible for PEP, 798 (69 at high risk and 729 at unknown risk) were offered treatment. Acceptance rates were 66.7% (n=46) and 41.3% (n=301) for participants at high risk and unknown risk, respectively. Participants at high risk were 2.2 times more likely to accept PEP than those at unknown risk (adjusted odds ratio 2.2; 95% confidence interval 1.2-4.0; P=0.01). Overall, 23.9% high-risk (n=11) and 33.2% unknown-risk participants (n=100) completed PEP (P=0.20). Predictors of acceptance and completion included assault by a stranger and participant anxiety. AEs were common, with 77.1% of participants reporting grade 2-4 symptoms. CONCLUSION: A province-wide standardized program of universal HIV counselling and offering of PEP to sexual assault survivors with frequent follow up was successfully implemented and feasible.


Subject(s)
Anti-HIV Agents/administration & dosage , Anti-HIV Agents/pharmacology , HIV Infections/prevention & control , Rape , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cohort Studies , Drug Combinations , Female , Humans , Lamivudine/administration & dosage , Lamivudine/pharmacology , Lopinavir , Male , Middle Aged , Ontario , Pyrimidinones/administration & dosage , Pyrimidinones/pharmacology , Risk Factors , Zidovudine/administration & dosage , Zidovudine/pharmacology
3.
AIDS Patient Care STDS ; 22(3): 213-9, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18290755

ABSTRACT

We sought to identify and review the clinical features and treatment outcomes of eight recent cases of otosyphilis in HIV-positive patients seen in Toronto. All patients reported tinnitus, and seven (87.5%) reported subjective hearing loss. Not taking auditory findings into consideration, four patients would be classified as having secondary syphilis, three patients as having early latent syphilis, and one patient as having latent syphilis of unknown duration. The median CD4 cell count was 370 x 10(6)/L. All patients were treated with intravenous aqueous penicillin G with regimens recommended for the treatment of neurosyphilis; four patients received adjunctive steroids. All eight patients experienced improvement in tinnitus and four of the seven (57.1%) patients with symptomatic hearing loss also experienced improvement. Otosyphilis can occur in HIV-positive individuals despite high CD4 cell counts, and is potentially reversible. Increased awareness of uncommon manifestations of syphilis in high-risk individuals is warranted to prompt appropriate investigation and treatment.


Subject(s)
Ear Diseases/complications , HIV Infections/complications , HIV-1 , Hearing Loss/etiology , Syphilis/complications , Adult , Anti-Bacterial Agents/therapeutic use , Ear Diseases/drug therapy , Ear Diseases/physiopathology , Female , Hearing Loss/classification , Hearing Loss/drug therapy , Humans , Male , Ontario , Penicillin G Benzathine/therapeutic use , Syphilis/classification , Syphilis/drug therapy , Treatment Outcome , Urban Population
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