Trends in different contraception methods among women attending the Melbourne Sexual Health Centre from 2011 to 2020.

OBJECTIVES: The efficacy and availability of contraception have changed in the last several decades; however, unintended pregnancies continue to be an issue in Australia. This study aimed to describe trends in contraception in women attending a sexual health service over 9 years. STUDY DESIGN: Repeated cross-sectional study. METHODS: Women aged 16-49 years attending Melbourne Sexual Health Centre between 2011 and 2020 were included. Women were asked what methods of contraception they currently use. Contraception were categorised into long-acting reversible contraception (LARC; e.g. intrauterine devices and implants classified as highly effective), moderately effective contraception (e.g. oral contraception pill), less effective contraception (e.g. condom and withdrawal) and no contraception, as defined by US Centers for Disease Control and Prevention guidelines. Multivariable logistic regression was used to examine the factors associated with the use of moderate-high-efficacy contraception. RESULTS: A total of 38,288 women were included with a median age of 25 (interquartile range: 22-29). Between 2011 and 2020, there was a decreasing trend in condom (63.3%-56.1%; Ptrend <0.001) and oral contraception (27.2%-20.5%; Ptrend <0.001) use, whilst there was an increasing trend in the use of LARCs: implant (4.6%-6.0%; Ptrend = 0.002) and intrauterine device (2.8%-11.8%; Ptrend <0.001). Increasing age was associated with decreased odds of using moderate-high-efficacy contraception (Ptrend <0.001). Compared with Oceanian-born women, Asian (adjusted odds ratios [aOR] = 0.63, 95% confidence interval [CI]: 0.56-0.72) and Middle Eastern-born women (aOR = 0.60, 95% CI: 0.48-0.74) had lower odds of using moderate-high-efficacy contraception, whilst European (aOR = 1.23, 95% CI:1.07-1.41) and North American-born women (aOR = 1.51, 95% CI: 1.22-1.87) had higher odds of using moderate-high-efficacy contraception. CONCLUSIONS: Between 2011 and 2020, LARC use has increased, whilst less effective contraceptives, such as condom and oral contraception, have decreased among women at Melbourne Sexual Health Centre. Further research is required to understand age and ethnic disparities in contraception methods for future family planning programmes.

Methamphetamine and AIDS: 1HMRS studies in a feline model of human disease.

Potential interactions between psychostimulant drugs and infection with feline immunodeficiency virus (FIV) on brain metabolism were evaluated. Four groups of cats were studied: control, FIV positive, methamphetamine (MA) exposed, and FIV positive plus MA exposed. Frontal gray matter, frontal white matter, and caudate brain extracts were studied with proton magnetic resonance spectroscopy (1HMRS). In the frontal white matter, FIV-infected cats showed decreases in creatine and choline, while MA-treated cats had elevated gamma-aminobutyric acid (GABA). The decreased glutamate in FIV cats normalized with MA exposure. FIV and MA both affect brain metabolites individually and combined. 1HMRS is useful for evaluating the effects of FIV and drug abuse in the brain.

Conversion of poorly immunogenic malaria repeat sequences into a highly immunogenic vaccine candidate.

The recent success of a Plasmodium falciparum malaria vaccine consisting of circumsporozoite protein (CSP) T and B cell epitopes has rekindled interest in the development of a pre-erythrocytic vaccine. In order to optimize immunogenicity, well-characterized CSP-specific neutralizing B cell epitopes and a universal T cell epitope were combined with an efficient and flexible particulate carrier platform, the hepatitis B core antigen (HBcAg), to produce a novel pre-erythrocytic vaccine candidate. The vaccine candidate, V12.PF3.1, is a potent immunogen in mice eliciting unprecedented levels (greater than 10(6) titers) of sporozoite-binding antibodies after only two doses. The anti-sporozoite antibodies are long lasting, represent all IgG isotypes, and antibody production is not genetically restricted. CSP-specific CD4+ T cells are also primed by V12.PF3.1 immunization in a majority of murine strains. Furthermore, the hybrid HBcAg-CS particles can be produced inexpensively in bacterial expression systems. These and other characteristics suggest that V12.PF3.1 represents an efficient and economical P. falciparum vaccine candidate for use separately or in combination with other formulations.

Partial characterization and tissue distribution of the feline mu opiate receptor.

Heroin abuse is a common route of acquiring HIV-1 infection. However, the effects of opiates on lentivirus disease progression are not well understood. Feline immunodeficiency virus is recognized as a good animal model for HIV-1, but characterization of the opiate receptor system in cats is lacking. Here we report the partial sequencing of the feline mu opiate receptor (MOR) and demonstrate a homology of 92 and 93% to the published human MOR sequences. Additionally, MOR transcripts were detected in the feline brain and tonsil but not in the spleen. Also, specific receptor ligand interactions were observed using microphysiometry.

Methamphetamine and HIV-1: potential interactions and the use of the FIV/cat model.

The interaction of methamphetamine with human immunodeficiency virus (HIV), the aetiologic agent of Acquired Immune Deficiency Syndrome (AIDS), has not been thoroughly investigated. However, increasingly, a larger proportion of HIV infected individuals acquire the virus through methamphetamine use or are exposed to this drug during their disease course. In certain populations, there is a convergence of methamphetamine use and HIV-1 infection; yet our understanding of the potential effects that simultaneous exposure to these two agents have on disease progression is extremely limited. Studying the interactions between methamphetamine and lentivirus in people is difficult. To thoroughly understand methamphetamine's effects on lentivirus disease progression, an animal model that is both clinically relevant and easily manipulated is essential. In this report, we identified potential problems with methamphetamine abuse in individuals with a concurrent HIV-1 infection, described the Feline Immunodeficiency Virus (FIV)/cat model for HIV-1, and reported our early findings using this modelling system to study the interaction of methamphetamine and lentivirus infections.

Borna disease virus persistence causes inhibition of glutamate uptake by feline primary cortical astrocytes.

Borna disease virus (BDV), a nonsegmented, negative-stranded (NNS) RNA virus, causes central nervous system (CNS) disease in a broad range of vertebrate species, including felines. Both viral and host factors contribute to very diverse clinical and pathological manifestations associated with BDV infection. BDV persistence in the CNS can cause neurobehavioral and neurodevelopmental abnormalities in the absence of encephalitis. These BDV-induced CNS disturbances are associated with altered cytokine and neurotrophin expression, as well as cell damage that is very restricted to specific brain regions and neuronal subpopulations. BDV also targets astrocytes, resulting in the development of prominent astrocytosis. Astrocytes play essential roles in maintaining CNS homeostasis, and disruption of their normal activities can contribute to altered brain function. Therefore, we have examined the effect of BDV infection on the astrocyte's physiology. We present here evidence that BDV can establish a nonlytic chronic infection in primary cortical feline astrocytes that is associated with a severe impairment in the astrocytes' ability to uptake glutamate. In contrast, the astrocytes' ability to uptake glucose, as well as their protein synthesis, viability, and rate of proliferation, was not affected by BDV infection. These findings suggest that, in vivo, BDV could also affect an important astrocyte function required to prevent neuronal excitotoxicity. This, in turn, might contribute to the neuropathogenesis of BDV.

Effects of multiple acute morphine exposures on feline immunodeficiency virus disease progression.

Drug abuse is a common method of human immunodeficiency virus type 1 transmission, but the role of opiates on lentivirus disease progression is not well understood. The feline immunodeficiency virus (FIV)/cat system was used to model the weekend opiate abuser: the nondependent, nonaddicted, and nontolerant person. Sixteen cats were placed into 4 groups: FIV only, morphine only, morphine/FIV, and controls. Multiple acute morphine exposure did not increase the severity of early lentivirus infection. On the contrary, it delayed or moderated the FIV-induced disease progression. Although the animals were exposed to only 1 injection of morphine per day for 2 consecutive days per week, the morphine-treated FIV-infected animals had a delayed onset of the FIV-induced lymphadenopathy, did not develop or had a significant delay in the FIV-induced effects on brain stem auditory evoked potentials, and demonstrated a trend toward decreased virus load.

Exogenous glucocorticoids alter parameters of early feline immunodeficiency virus infection.

Feline immunodeficiency virus (FIV), a lentivirus, causes progressive immunosuppression and neurologic dysfunction in cats. Glucocorticoids are common therapeutic agents that are also immunosuppressive, and their use might enhance the pathogenic effects of lentivirus infections. Methylprednisolone acetate, a long-acting glucocorticoid, was administered to cats before FIV inoculation, and the course of early infection was monitored. The humoral immune response to FIV was not affected by corticosteroid treatment, but CD8+ cell-mediated antiviral activity was poor in cultures from FIV-infected cats treated with methylprednisolone. Steroid-treated cats had higher plasma viral RNA levels than untreated cats during acute viremia. In contrast, FIV-associated changes in brain stem auditory-evoked potentials were slow to develop in the methylprednisolone-treated cats. Methylprednisolone treatment of cats with established FIV infections appeared to reverse these neurophysiologic changes. These results emphasize the complexity of host-lentivirus interactions and suggest potential advantages and drawbacks of using glucocorticoids in lentivirus infections.

Replication rate of feline immunodeficiency virus in astrocytes is envelope dependent: implications for glutamate uptake.

Feline immunodeficiency virus (FIV) induces neurological abnormalities in domestic cats. Previously, we demonstrated that two disparate strains of FIV (FIV-34TF10 and FIV-PPR) varied greatly in the ability to replicate in feline cortical astrocytes. To investigate the impact of the env region on the replication efficiency of these strains, we constructed two env chimera viruses, FIV-34TF10-PPRenv and FIV-PPR-34TF10env, to infect feline cortical astrocytes in vitro. Although all of these viruses infected cortical astrocytes, the efficiency of replication depended on strain, and the env region played an essential role. The viruses containing the env of 34TF10, FIV-34TF10, and FIV-PPR-34TF10env had the greatest replication rate, whereas the viruses containing the env of PPR replicated at a lower level. Other viral regions had modulatory effects on the replication rate, with the FIV-PPR genome providing a slight replication advantage over the FIV-34TF10 genome. We also monitored the effects of these viruses on an important astrocyte function, glutamate uptake; all viruses significantly decreased this activity, but only the viruses containing the env of PPR significantly impaired glutamate uptake without altering the culture viability. These results may be particularly relevant in the context of lentivirus-induced central nervous system disease in which a selective breakdown of astroglial function may contribute to neurodegeneration.

Feline immunodeficiency virus envelope protein (FIVgp120) causes electrophysiological alterations in rats.

Close to 20% of the patients infected with the AIDS virus develops neurological deficit; eventhough HIV does not invade neurons. Consistently with the neurological deficit, HIV(+) subjects show abnormalities in brainstem auditory and visual evoked potentials (BSAEP and VEP) and in sleep patterns. The HIV-derived glycoprotein 120 has been postulated as a neurotoxic; therefore, it may be playing a crucial role in the generation of BSAEP and VEP, as well as in sleep disturbances. To study the role of the virus-derived proteins on the development of these electrophysiological signals' alterations, we have used the feline immunodeficiency virus (FIV)-derived gp120 and evaluated the changes in these electrophysiological signals. We employed 15 adult male Sprague-Dawley rats (250-350 g), chronically implanted for evoked potential and sleep recordings. Results showed that the i.c.v. administration of FIVgp120 (5 ng/10 microliter) produces changes in the latency of both cortical auditory evoked potentials (CAEPs) and VEPs and a decrease in both REM sleep and SWS. These data support the notion that FIVgp120 is neurotoxic to the central nervous system of cats and rats and that this protein suffices to cause electrophysiological alterations. In addition, it suggests that a similar effect may be occurring in humans as a result of HIVgp120's neurotoxic effects.

Neurotoxic effects of feline immunodeficiency virus, FIV-PPR.

FIV is a lentivirus of domestic cats that causes neurologic disorders which are remarkably similar to those found in HIV-1 infected people. Using feline neuron cultures, we investigated the potential of both FIV virus and FIV-Env protein to cause neuronal damage through the excitotoxicity mechanism. The neuron swelling and lactate dehydrogenase (LDH) release assays were used as measures of cellular damage. The effects of FIV Env protein on glutamate receptor mediated increases in intracellular calcium were also examined. We found that FIV virus and FIV-Env protein significantly increased LDH release from the neuron cultures. Additionally, an increase in neuron size was detected in the cultures exposed to the virus, while swelling did not occur with exposure to either saline, denatured virus, or FIV-Env by itself. However, when both 20 microM glutamate and the FIV-PPR Env protein were added to the culture, a significant increase in neuron cell size was observed. The NMDA calcium signals were similar in general form between the control and FIV-PPR Env exposed cultures. However, the FIV - PPR Env protein treated cultures resulted in significant enhancement of the NMDA induced calcium signal. Our results indicate that FIV Env protein (either within the virion or baculovirus expressed) induced neurotoxicity as measured by neuron swelling and LDH release assays and that exposure of feline neurons to FIV Env protein alters the handling of intracellular calcium. These findings help to validate the FIV/cat system as a potential animal model for evaluating therapeutic approaches that target the excitotoxicity mechanisms of lentivirus induced CNS disease.

Effects of feline immunodeficiency virus on astrocyte glutamate uptake: implications for lentivirus-induced central nervous system diseases.

Feline immunodeficiency virus (FIV) is a lentivirus of domestic cats that causes a spectrum of diseases remarkably similar to AIDS in HIV-infected humans. As part of this spectrum, both HIV-1 and FIV induce neurologic disorders. Because astrocytes are essential in maintaining the homeostasis of the central nervous system, we analyzed FIV for the ability to infect feline astrocytes. Through immunocytochemistry and reverse transcriptase activity, it was demonstrated that two molecular clones of FIV (FIV-34TF10 and FIV-PPR) produce a chronic low level productive infection of feline astrocyte cultures. To investigate the consequences of this infection, selected astrocyte functions were examined. Infection with FIV-34TF10 significantly decreased the ability of astrocytes to scavenge extracellular glutamate (with a peak inhibition of 74%). The effects of the infection did not appear to be a result of toxicity but rather were more selective in nature because the glucose uptake function of the infected astrocyte cultures was not altered. Our data demonstrate that FIV productively infected, at a low level, feline astrocyte cultures, and as a consequence of this infection, an important astroglial function was altered. These findings suggest that a chronic low grade infection of astrocytes may impair the ability of these cells to maintain homeostasis of the central nervous system that, in turn, may contribute to a neurodegenerative disease process that is often associated with lentivirus infections.

Cortical neuronal cytoskeletal changes associated with FIV infection.

HIV-1 infection is often complicated by central nervous system (CNS) dysfunction. Degenerative neuronal changes as well as neuronal loss have been documented in individuals with AIDS. Feline immunodeficiency virus (FIV) infection of cats provides a model for both the immune and the central nervous system manifestations of HIV infection of humans. In this study we have examined neurons in the frontal cortex of feline immunodeficiency virus-infected cats and controls for immunoreactivity with SMI 32, an antibody recognizing a non-phosphorylated epitope on neurofilaments. We noted a significant increase in the number of immunoreactive pyramidal cells in infected animals compared to controls. The changes seen in the neuronal cytoskeleton as a consequence of the inoculation with FIV were similar to those seen in humans undergoing the normal aging process as well as those suffering from neurological diseases, including Alzheimer's and dementia pugilistica. The changes we noted in the feline brain were also similar to that reported in animals with traumatic injuries or with spontaneously occurring or induced motor neuron diseases, suggesting that the increase in reactivity represents a deleterious effect of FIV on the central nervous system.

Neurologic dysfunctions caused by a molecular clone of feline immunodeficiency virus, FIV-PPR.

FIV is a lentivirus of domestic cats that causes a spectrum of diseases that is remarkably similar to the clinical syndrome produced by HIV infection in people. Both HIV and FIV has been shown to cause neurologic dysfunction. Specific Pathogen-Free (SPF) cats were placed into one of three groups: FIV-PPR infected; DU-FIV-PPR (a dUTPase mutant of the FIV-PPR clone) infected; or an age-matched control group. In both infected groups, the general clinical signs of infection included lymphadenopathy, oral ulcerations, rough hair coat, and conjuntivitis. Specific neurological changes in the FIV-PPR infected cats included hind limb paresis; delayed righting and pupillary reflexes; behavioral changes; delayed visual and auditory evoked potentials; decreased spinal and peripheral nerve conduction velocities; and marked alterations in sleep patterns. Most of these changes were also observed in the DU-FIV-PPR infected cats. However, these cats tended to have a slightly less severe disease. In this study, we have demonstrated that an infectious molecular clone of FIV closely parallels the disease course of wild type FIV-infected cats. By using a knockout gene mutant of this clone, we were able to demonstrate that the dUTPase gene is not essential for neuropathogenesis. Further use of the FIV-PPR clone should prove useful in determining the essential viral elements that are important in the neuropathogenesis of lentiviral infections.

Selection and characterization of a mutant of feline immunodeficiency virus resistant to 2',3'-dideoxycytidine.

We have selected and plaque purified a mutant of feline immunodeficiency virus (FIV) that is resistant to 2',3'-dideoxycytidine (ddC). This mutant was selected in cultured cells in the continuous presence of 25 microM ddC. The mutant, designated DCR-5c, was fourfold resistant to ddC, threefold resistant to 2',3'-dideoxyinosine, and more than fourfold resistant to phosphonoformic acid. DCR-5c displayed little or no resistance to (-)-beta-2',3'-dideoxy-3'-thiacytidine, 3'-azido-3'-deoxythymidine, or 9-(2-phosphonylmethoxyethyl) adenine. Reverse transcriptase purified from DCR-5c was less susceptible to inhibition by ddCTP, phosphonoformic acid, ddATP, or azido-dTTP than the wild-type FIV reverse transcriptase. Sequence analysis of DCR-5c revealed a single base change (G to C at nucleotide 2342) in the reverse transcriptase-encoding region of FIV. This mutation results in substitution of His for Asp at codon 3 of FIV reverse transcriptase. The role of this mutation in ddC resistance was confirmed by site-directed mutagenesis.

Increased mutation frequency of feline immunodeficiency virus lacking functional deoxyuridine-triphosphatase.

Feline immunodeficiency virus (FIV) encodes the enzyme deoxyuridine-triphosphatase (DU; EC 3.6.1.23) between the coding regions for reverse transcriptase and integrase in the pol gene. Here, we report the in vivo infection of cats with a DU- variant of the PPR strain of FIV and compare its growth properties and tissue distribution with those of wild-type FIV-PPR. The results reveal several important points: (i) DU- FIV is able to infect the cat, with kinetics similar to that observed with wild-type FIV; (ii) both wild-type and DU- FIV-infected specific-pathogen free cats mount a strong humoral antibody response which is able to limit the virus burden in both groups of animals; (iii) the virus burden is reduced in the DU- FIV-infected cats, particularly in tissues such as spleen and salivary gland; and (iv) the mutation frequency in DU- FIVs integrated in the DNA of primary macrophages after 9 months of infection is approximately 5-fold greater than the frequency observed in DU- FIV DNA integrated in T lymphocytes. Mutation rate with wild-type FIV remains the same in both cell types in vivo. The dominant mutations seen in macrophages with DU- FIV are G-->A base changes, consistent with an increased misincorporation of deoxyuridine into viral DNA of DU- FIVs during reverse transcription. Because this enzyme is absent from human immunodeficiency virus type 1 and other primate lentiviruses, virus replication in cell environments with low DU activity may lead to increased mutation and contribute to the rapid expansion of the viral repertoire.

Feline immunodeficiency virus as a model for study of lentivirus infection of the central nervous system.

Feline immunodeficiency virus infects the CNS and results in predictable pathophysiology strikingly similar to that seen with HIV-1 infection of humans. The observed pathophysiology is mimicked in several physiologically assessed modalities, further supporting the validity of the feline model. Peripheral and control evoked potential findings and the occurrence of the sleep architecture changes in both cat and human disease provide an intriguing focus for further investigation. Although structurally diverse in an absolute sense, FIV and HIV-1 share basic structural features and commonalities of their life cycle. It is likely that by understanding the common mechanisms by which these lentiviruses influence CNS function, a more complete understanding of the neurological deficits seen in HIV-1 infected patients will be obtained. The cat model is particularly valuable for study of CNS disease, since it allows detailed analyses of events during the acute phase of infection, under circumstances in which the nature and timing of the infection are carefully controlled. The availability of molecular clones for mutational analysis will facilitate mapping of genomic regions critical to the perturbation of CNS function. It is suggested that development of intervention strategies in the cat model will yield treatment modalities directly applicable to HIV-1 infection of humans.