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Objective To describe prevalent and persistent oncogenic human papillomavirus (HPV) types detected in women living with HIV (WLWH) in Canada, including women with cervical dyskaryosis, and to determine predictors of type-specific HPV persistence. Methods Women and girls living with HIV, recruited from 14 sites of HIV care across Canada, were included in a sub-analysis of a prospective vaccine immunogenicity cohort study (two HPV DNA results, at least one cervical cytology result pre-vaccination). Demographic and clinical data were collected alongside cervical samples for cytology and HPV DNA typing between November 25, 2008, and May 19, 2015. Results Pre-vaccination, HPV16 and HPV52 were the most prevalent oncogenic HPV types. Of the 252 women and girls who met the eligibility criteria, 45% were infected with at least one oncogenic HPV type and one-third of participants had a persistent oncogenic infection. HPV16, 45, and 52 were the most frequently persistent types. Seventeen percent of women had persistent infections with oncogenic HPV types not within currently available vaccines (HPV35/39/51/56/59/68/82). Lower CD4 count significantly predicted HPV persistence (P=0.024). Cervical cytology results were normal for 82.9% of participants, atypical squamous cells of undetermined significance for 2.4%, low-grade squamous intraepithelial lesions for 11.5%, and high-grade squamous intraepithelial lesions for 2.8%. Conclusion Unvaccinated WLWH were infected with a wide range of oncogenic HPV types. The findings highlighted the importance of optimal treatment of HIV and continued cervical cancer screening as key steps toward the global elimination of cervical cancer.

Objectives Conflicting results have been reported regarding the ability of valproic acid (VPA) to reduce the size of HIV reservoirs in patients receiving suppressive highly active antiretroviral therapy (HAART). In a randomized multicentre, cross-over study, we assessed whether adding VPA to stable HAART could potentially reduce the size of the latent viral reservoir in CD4 T cells of chronically infected patients. Methods A total of 56 virologically suppressed patients were randomly assigned either to receive VPA plus HAART for 16 weeks followed by HAART alone for 32 weeks (arm 1; n = 27) or to receive HAART alone for 16 weeks and then VPA plus HAART for 32 weeks (arm 2; n = 29). VPA was administered at a dose of 500 mg twice a day (bid) and was adjusted to the therapeutic range. A quantitative culture assay was used to assess HIV reservoirs in CD4 T cells at baseline and at weeks 16 and 48. Results No significant reductions in the frequency of CD4 T cells harbouring replication-competent HIV after 16 and 32 weeks of VPA therapy were observed. In arm 1, median (range) values of IU per log10 billion (IUPB) cells were 2.55 (range 1.20–4.20), 1.80 (range 1.0–4.70) and 2.70 (range 1.0–3.90; P = 0.87) for baseline, week 16 and week 48, respectively. In arm 2, median values of IUPB were 2.55 (range 1.20–4.65), 1.64 (range 1.0–3.94) and 2.51 (range 1.0–4.48; P = 0.50) for baseline, week 16 and week 48, respectively. Conclusions Our study demonstrates that adding VPA to stable HAART does not reduce the latent HIV reservoir in virally suppressed patients.

Guidelines recommend that when soft-gelatin capsules of lopinavir/ritonavir are co-administered with CYP3A4-inducing agents, doses should be increased to 4 capsules (533 mg/133 mg) twice daily. No evidence is available to guide dosing of lopinavir/ritonavir in tablet formulation in this setting. A single-center study is conducted to compare the pharmacokinetics of high-dose lopinavir/ritonavir in 34 patients on stable HAART regimens including 4 soft-gelatin capsules twice daily who then switch to 3 tablets (600 mg/150 mg) twice daily. Median C(min) on soft-gelatin capsule and tablets is 4700 ng/mL (interquartile range [IQR] 2310, 6000 ng/mL) and 5640 ng/mL (IQR 4290, 8080 ng/mL), respectively, for those on inducing agents (n = 17). For patients not on inducing agents (n = 17), median C(min) on soft-gelatin capsule and tablets is 5170 ng/mL (IQR 3640, 6210 ng/mL) and 5640 ng/mL (IQR 4290, 8080 ng/mL), respectively. Among treatment-experienced patients on lopinavir/ritonavir capsules 533/133 mg twice daily, a switch to tablets 600/150 mg twice daily produces comparable pharmacokinetics, regardless of whether they receive concomitant CYP3A4-inducing antiretroviral agents.

Background Highly active antiretroviral therapy (HAART) with protease inhibitors (PI) is successful in suppressing viral replication, but may lead to a range of metabolic abnormalities associated with cardiovascular disease (CVD). Objectives The first objective of the study was to compare baseline demographic and clinical characteristics between PI users and non-PI users referred to a specialized metabolic clinic during 1999–2003. The second objective was to assess the associations of prescription drugs and fish oil with dyslipidaemia and to determine whether or not patients achieved treatment targets during 6 months of treatment. Methods A retrospective analysis was performed using two sets of charts based on standardized forms with entries for personal data, drug treatment and clinical history. Anonymous linkage with the British Columbia HIV/AIDS Drug Treatment Program and the hospital laboratory was performed to gather information about HAART prescriptions and blood work. Results In total, 237 patients were included in the study. There were few differences in any demographic or clinical factors between PI users and non-PI users. Compared with controls not taking lipid-lowering drugs or fish oil (n=48), statins appeared to be the only agent that was significantly associated with a reduced total cholesterol concentration (−15.6%; P=0.009). Fibrate treatment was associated with the largest reduction of triglyceride concentration (−37.4%; P=0.012), closely followed by fish oil (n=18;−32%; P=0.027). Six-month treatment success rates ranged between 17 and 43% of patients for total cholesterol (

Objective To examine differences among four protease inhibitor (PI)-based drug regimens in adherence to therapy and rate of achievement of virological suppression in a cohort of antiretroviral-naive patients initiating highly active antiretroviral therapy (HAART). Methods Participants were antiretroviral-naive and were first dispensed combination therapy containing two nucleosides and a ritonavir (RTV)-boosted PI, or unboosted nelfinavir, between 1 January 2000 and 30 September 2003. Logistic regression analysis was used to examine associations between the prescribed PI and other baseline factors associated with being >90% adherent to therapy and then to determine the associations of prescribed drug regimen, adherence to therapy and baseline variables with the odds of achieving two consecutive viral loads of

Three non-nucleoside reverse transcriptase inhibitors (NNRTIs) are currently available for treatment of HIV-1 as part of combination antiretroviral therapy. Oral dosing is administered three times daily for delavirdine (DLV), twice daily for nevirapine (NVP), and once daily for efavirenz (EFV). Rash is a common side effect of all three NNRTIs, and early CNS side effects are also frequent with EFV. Hepatotoxicity is relatively uncommon but requires appropriate monitoring. Drug interactions mediated by the cytochrome P450 system are an important consideration when the NNRTIs are administered concomitantly with other drugs, including protease inhibitors (PIs). HIV strains with reduced susceptibility to NNRTIs can occur with a single mutation in the reverse transcriptase (RT) gene. The available NNRTIs exhibit overlapping genotypic resistance patterns, but newer agents may overcome this problem. NNRTIs have been studied in combination with nucleoside RT inhibitors for first-line HIV therapy, where they have shown at least equivalent antiviral efficacy compared with PI-based regimens over 1-2 years of therapy. NVP and EFV have also been studied as a replacement for a PI within a virologically successful regimen, with the aim of preventing or reducing PI toxicities and simplifying the dosing regimen. Such 'switch' strategies are successful for certain patients in maintaining virologic suppression for 6 months or more and result in varying degrees of improvement in PI-associated toxicities. NNRTIs may offer a benefit when included in salvage regimens for patients failing PI-based therapy, particularly in patients who have not previously been treated with NNRTIs. NVP has been shown to have a substantial favourable impact on the rate of vertical HIV-1 transmission with a simple, cost-effective regimen.

of results Six patients switched from tenofovir to entecavir in 2007. All patients were male with a median age of 49 yrs (IQR 46–58 yrs) and a median CD4 count of 500 cells/mm3 (IQR 253–658 cells/mm3). All patients were hepatitis Be antigen positive, and had undetectable HBV viral loads while on tenofovir therapy prior to initiation of entecavir. 5/6 patients had prior HBV DNA samples available for genotypic testing; 100% revealed evidence of baseline lamivudine resistance (presence of L180 M + M204 V) but no evidence of entecavir-associated resistance mutations. Patients were treated with entecavir 1 mg daily or renallyadjusted equivalent. Lamivudine was maintained within the antiretroviral regimen of 5/6 patients. All patients experienced HBV rebound on entecavir. Median time to HBV virologic rebound was 2 months (range 1–11 months), and the median HBV DNA viral load at rebound was 226,012 copies/mL (IQR 6,771–492,237 copies/mL). Only one patient experienced a rise in ALT (to 143 IU/mL) at the time of initial HBV rebound. All patients maintained HIV virologic suppression during the substitution period and at the time of HBV rebound.