Lived experience of gay men caring for others with HIV/AIDS : living, loving and dying in the era of HIV/AIDS

This thesis explored gay male carers’ experience of caring for their partner, brother or friend who had HIV/AIDS. Through using phenomenological methodology (van Manen, 1990), the day-to-day caring experiences were uncovered. The data gathered were then analysed through a nursing ‘lens’, with the concept of stigma as an anchoring point. The dual stigmas of homophobia and AIDS phobia impacted on the daily lives of these men as they cared for their loved one. The research identified six themes. These were: 1) the relationship; 2) coping with HIV and AIDS; 3) the corporal impact of HIV/AIDS; 4) experiences of carers including the absence of others; 5) living daily with the virus: Demands of people living with HIV/AIDS (PLWHA); and 6) saying goodbye, but wanting to keep the memory alive. The caring these men undertook, for which they were frequently unprepared, was intensive and complex, but because of their commitment and love they battled on. Because of a sense of shame associated with AIDS phobia on the part of the PLWHA, the carer often had to undertake this care in isolation, without support from family, friends or home health care agencies. The carers struggled with not only the demands of day-to-day care, but also with non-acceptance from family, both of the nature of the relationship with their partner and of their homosexuality. Family members were forced, often with great difficulty, to acknowledge the close commitment the men had to each other. Recognition that one had a terminal disease, HIV/AIDS was also required. The fear of potential transmission was high among carers, friends and family members. Notably, there was an absence of blame on the part of the carer towards his partner for contracting HIV/AIDS. The physical decline and marking of the body further stigmatised the PLWHA, which added to carers’ burdens. They endeavoured to minimise the physical decline in their partner, so he could continue to pass as healthy, and attempted to make the day-to-day living as normal as possible. The methods of combating weight loss and opportunistic infections meant frequent medical appointments, complex intensive medical procedures and help with personal care, which was undertaken at home largely without support from health care staff. Carers frequently struggled also with their partner’s denial of being ill. One strategy all carers used was to escape with their partners from their everyday life in Melbourne and attempt metaphorically to leave the HIV/AIDS behind; this was a time when they could rekindle their life together as it was before HIV/AIDS came into their lives. Some carers chose to holiday without their partner, to give themselves a break from the day-to-day caring, while others planned and took holidays with their partner. The decline of the health in the PLWHA meant that family members had to recognise and accept both the nature of the relationship and the presence of the disease. This recognition and acceptance often came only when the partner was very ill, even at the point of dying. Carers and their partners discussed the potential use of euthanasia, as a means of ending the final phase of life with some dignity. One carer and his partner used euthanasia, despite its illegal status. The main concern for all carers was providing comfort and a reduction in the pain associated with HIV/AIDS for the partner. The widespread grief associated with HIV/AIDS was evident amongst these carers. All had known other gay men who had died, some carers own partner had died, or was about to die. There was an overwhelming sense of grief, which at times was repressed as a means of coping day-to-day. All carers felt it was important and necessary to remember those lost to HIV/AIDS through the various public memorials, as they did not want their partner to be just another faceless person lost to this disease. This phenomenological study of carers’ experience highlights the need for health care workers to be aware of the differing strategies that gay men use to cope with HIV/AIDS. While it may seem that the carers are coping with care of their partner, the outer façade is not always an accurate portrayal of the true situation. Health care workers should enquire as to the assistance these carers need from health care services in order to continue to care for their loved one. Such assistance can be the simple recognition of the partner and acceptance of them as part of the PLWHA’s network; this inclusion and acceptance is half the battle.

General practitioner and the control of sexually transmissible infections

Sexually transmissible infections (STIs), one of the major preventable health problems affecting the Australian population, are often asymptomatic and, if undetected, can cause sub-fertility, infertility and chronic morbidity. In addition to these significant and costly consequences, STIs increase the risk of transmission of HIV. Given that 80% of Australian patients attend their General Practitioner (GP) each year, GPs are well placed to have a significant impact on STI transmission by diagnosing and treating both asymptomatic and symptomatic disease. Good professional practice would suggest that all GPs will undertake certain actions when they are consulted by a patient who either has symptoms of an STI or who appears to be at risk of acquiring an STI. This expectation is based on the premise that all GPs share the same detailed knowledge of STI risk factors and symptoms. It assumes that they will have no difficulty in eliciting such information from the patient, that the patient will comply with STI testing and treatment and that the patient will return for follow-up, to ensure that they and their sexual partners have been adequately treated. Given the constraints of the real world in which general practice exists, the sensitive nature of sexual health, and the stigma associated with STIs, there are many barriers to achieving such an outcome. My own previous research has highlighted some of the difficulties experienced by GPs in the area of STI control. This study has used data from four different sources (policy and stakeholder documents, literature, key informant interviews and my own past research) to examine ideal practice and actual practice in the prevention and treatment of STIs. A number of discrepancies were identified, and from these arose a series of recommendations for ways of making STI control in general practice less complex. To ensure that the results of the study were firmly embedded in the reality of general practice, comments on the recommendations were sought from GPs employed in a variety of practice settings, including those with low STI caseloads. These comments were used to modify the recommendations to ensure they would offer a practical and effective contribution to STI control in Victoria.

Baseline comorbidities in a population-bases cohort of rheumatoid arthritis patients receiving biological therapy: data from the Australian Rheumatology Association database

Aims: To describe the baseline characteristics of an Australian population-based cohort of rheumatoid arthritis (RA) patients commencing biological therapy.

Methods: Descriptive analysis from the Australian Rheumatology Association Database (ARAD).

Results: Up to October 2006, there were 681 RA patients taking biologics enrolled in ARAD. Baseline data were available for 624 (72% female, mean (SD) age 57.0 (12.5) years). Of these, 59.5% reported at least one comorbid condition, most commonly hypertension (35.7%) and osteoporosis (30.4%); 61 (9.8%) had a history of malignancy (35 nonmelanoma skin, 5 breast, 4 bowel, 5 cervix, 3 melanoma, 3 prostate and 1 each of lip, lung, myeloma, testis, uterus, vagina). Self-reported infections within the previous 6 months were common (71.5%).

Conclusions: History of comorbidities, including recent infections, is common among Australian RA patients commencing biologics, and 10% have a history of malignancy. This may impact future evaluations of health outcomes among this population, including attribution of adverse events of biologic therapy.

Safer injections, fewer infections : management of needles and sharps and occupational blood exposure in rural north Indian health settings

This study investigated injection practices and occupational exposure to blood in rural north Indian health settings. The findings highlighted a range of practices potentially contributing to the transmission of hepatitis and HIV to both patients and staff in these settings. Interventions need to focus on the development of organisational structures to support and facilitate safer practices.

Anti-tumour necrosis factor-α therapy for severe enteropathy in patients with common variable immunodeficiency (CVID)

We present three common variable immunodeficiency (CVID) patients with
severe inflammatory bowel disease of unknown aetiology, resistant to steroid
treatment, treated with infliximab.After exclusion of any infection, infliximab
was given at a dose of 5 mg/kg every 4 weeks for a 3 month induction followed
by every 4–8 weeks depending on clinical response. Two of these patients had
predominantly small bowel disease; they both showed clinical response to
infliximab with weight gain and improvement of quality of life scores. The
third patient had large bowel involvement with profuse watery diarrhea; this
patient improved dramatically within 48 hours of having infliximab
treatment. All three patients have been maintained on infliximab treatment
for between 5 and 53 months (mean 37 months) with no evidence of increased
susceptibility to infections in the patients with small bowel disease, although
the third patient developed two urinary tract infections and a herpes zoster
infection following therapy. This is the first small case series to show that
infliximab is a useful addition to current therapy in this rare group of patients
with potentially life threatening enteritis.

Immune reconstitution sarcoidosis presenting with hypercalcaemia and renal failure in HIV infection

An HIV-positive white man developed hypercalcaemia and renal failure 15 months after starting highly active antiretroviral therapy. Investigations showed systemic sarcoidosis affecting parotids, skin and kidneys. This presentation was thought to be a manifestation of immune reconstitution inflammatory syndrome, and the patient was successfully treated with corticosteroid therapy.

HIV-1 vaccine development : tackling virus diversity with a multi-envelope cocktail

A major obstacle to the design of a global HIV-1 vaccine is viral diversity. At present, data suggest that a vaccine comprising a single antigen will fail to generate broadly reactive B-cell and T-cell responses able to confer protection against the diverse isolates of HIV-1. While some B-cell and T-cell epitopes lie within the more conserved regions of HIV-1 proteins, many are localized to variable regions and differ from one virus to the next. Neutralizing B-cell responses may vary toward viruses with different i) antibody contact residues and/or ii) protein conformations while T-cell responses may vary toward viruses with different (i) T-cell receptor contact residues and/or (ii) amino acid sequences pertinent to antigen processing. Here we review previous and current strategies for HIV-1 vaccine development. We focus on studies at St. Jude Children's Research Hospital (SJCRH) dedicated to the development of an HIV-1 vaccine cocktail strategy. The SJCRH multi-vectored, multi-envelope vaccine has now been shown to elicit HIV-1-specific B- and T-cell functions with a diversity and durability that may be required to prevent HIV-1 infections in humans.

Diet high in monounsaturated fat does not have a different effect on arterial elasticity than a low-fat, high-carbohydrate diet

Objective : To compare the effects of a modified-fat diet high in monounsaturated fat, and a low-fat/high-carbohydrate diet on arterial elasticity.
Design : Randomized crossover design; each diet period was 1 month and a 2-week wash out period occurred in between.
Subjects/setting : Thirty healthy, free-living, nonsmoking men and women were recruited from the Melbourne, Australia, metropolitan region of Australia. Men were aged 35 to 55 years and postmenopausal women were aged 50 to 60 years and were not taking hormone replacement therapy. Twenty-eight subjects completed the study.
Intervention : Two diets of equal energy value: a modified-fat diet and a low-fat/high-carbohydrate diet; the modified-fat diet had 3 times more energy from monounsaturated fat.
Main outcome measures : Arterial elasticity and serum lipoprotein concentrations.
Statistical analysis : The general linear model was used to investigate overall effect and any carryover or order effects. Paired t test and the general linear model were used to compare the results from the 2 diet periods.
Results : High-density lipoprotein cholesterol concentration was significantly higher on the modified-fat diet than on the low-fat/low-carbohydrate diet. Arterial elasticity and concentrations of total cholesterol, low-density lipoprotein cholesterol, and triglycerides were not significantly different on the 2 diets.
Applications/conclusions : There is no evidence to favor a diet high in monounsaturated fat over a low-fat/high-carbohydrate diet because of an effect on arterial elasticity. Other changes in diet may be needed to cause a beneficial effect on arterial elasticity.

A multi-vector, multi-envelope HIV-1 vaccine

The St. Jude Children's Research Hospital (St. Jude) HIV-1 vaccine program is based on the observation that multiple, antigenically distinct HIV-1 envelope protein structures are capable of mediating HIV-1 infection. A cocktail vaccine comprising representatives of these diverse structures (immunotypes) is therefore considered necessary to elicit lymphocyte populations that prevent HIV-1 infection. This strategy is reminiscent of that used to design a currently licensed and successful 23-valent pneumococcus vaccine. Three recombinant vector systems are used for the delivery of envelope cocktails (DNA, vaccinia virus, and purified protein) and each of these has been tested individually in phase I safety trials. A fourth clinical trial, in which diverse envelopes and vectors are combined in a prime-boost vaccination regimen, has been FDA-approved and is expected to commence in 2007. This trial will continue to test the hypothesis that a multivector, multi-envelope vaccine can elicit diverse 8- and T-cell populations that can prevent HIV-1 infections in humans.

Early events of HIV-1 infection : can signalling be the next therapeutic target?

Intracellular signaling events are signposts of biological processes, which govern the direction and action of biological activities. Through millions of years of evolution, pathogens, such as viruses, have evolved to hijack host cell machinery to infect their targets and are therefore dependent on host cell signaling for replication. This review will detail our current understanding of the signaling events that are important for the early steps of HIV-1 replication. More specifically, the therapeutic potential of signaling events associated with chemokine coreceptors, virus entry, viral synapses, and post-entry processes will be discussed. We argue that these pathways may represent novel targets for antiviral therapy.

Novel alginate-enclosed chitosan–calcium phosphate-loaded iron-saturated bovine lactoferrin nanocarriers for oral delivery in colon cancer therapy

Aim: To develop polymeric-ceramic nanocarriers (NCs) in order to achieve oral delivery of the anticancer neutraceutical iron-saturated bovine lactoferrin (Fe-bLf) protein.

Materials & methods: Fe-bLf or paclitaxel (Taxol®) were adsorbed onto calcium phosphate nanocores, enclosed in biodegradable polymers chitosan and alginate. The Fe-bLf or Taxol-loaded NCs indicated as AEC–CP–Fe-bLf or AEC–CP–Taxol NCs, respectively, were made by combination of ionic gelation and nanoprecipitation. Size distribution, morphology, internalization and release profiles of the NCs were studied along with evaluation of in vitro and in vivo anticancer activities and compared with paclitaxel.

Results: AEC–CP–Fe-bLf NCs obtained spherical morphology and showed enhanced endocytosis, transcytosis and anticancer activity in Caco-2 cells in vitro. AEC–CP–Fe-bLf NCs were supplemented in an AIN 93G diet and fed to mice in both prevention and treatment human xenograft colon cancer models. AEC–CP–Fe-bLf NCs were found to be highly significantly effective when given orally, as a pretreatment, 1 week before Caco-2 cell injections. None of the mice from the AEC–CP–Fe-bLf NC-fed group developed tumors or showed any signs of toxicity, while the mice fed the control AIN 93G diet showed normal tumor growth. Fe-bLf or Taxol, when given orally in a diet as nanoformulations post-tumor development, showed a significant regression in the tumor size with complete inhibition of tumor growth later, while intratumoral injection of Taxol just delayed the growth of tumors. The pharmacokinetic and bioavailability studies indicated that nanoformulated Fe-bLf was predominantly present on tumor cells compared to non-nanoformulated Fe-bLf. Fe-bLf-loaded NCs were found to help in absorption of iron and thus may have utility in enhancing the iron uptake during iron deficiency without interfering with the absorption of calcium.

Conclusion: With the promising results of our study, the future potential of NC-loaded Fe-bLf in chemoprevention and in the treatment of human colon cancer, deserves further investigation for translational research and preclinical studies of other malignancies.

Unique IL-13Rα2-based HIV-1 vaccine strategy to enhance mucosal immunity, CD8(+) T-cell avidity and protective immunity.

We have established that mucosal immunization can generate high-avidity human immunodeficiency virus (HIV)- specific CD8þ T cells compared with systemic immunization, and interleukin (IL)-13 is detrimental to the functional avidity of these T cells. We have now constructed two unique recombinant HIV-1 vaccines that co-express soluble or membrane-bound forms of the IL-13 receptor a2 (IL-13Ra2), which can ‘‘transiently’’ block IL-13 activity at the vaccination site causing wild-type animals to behave similar to an IL-13 KO animal. Following intranasal/intramuscular prime-boost immunization, these IL-13Ra2-adjuvanted vaccines have shown to induce (i) enhanced HIV-specific CD8þ Tcells with higher functional avidity, with broader cytokine/chemokine profiles and greater protective immunity using a surrogate mucosal HIV-1 challenge, and also (ii) excellent multifunctional mucosal CD8þ T-cell responses, in the lung, genito-rectal nodes (GN), and Peyer’s patch (PP). Data revealed that intranasal delivery of these IL-13Ra2-adjuvanted HIV vaccines recruited large numbers of unique antigen-presenting cell subsets to the lung mucosae, ultimately promoting the induction of high-avidity CD8þ Tcells. We believe our novel IL-13R cytokine trap vaccine strategy offers great promise for not only HIV-1, but also as a platform technology against range of chronic infections that require strong sustained high-avidity mucosal/systemic immunity for protection.

Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1

Manifestations of viral infections can differ between women and men, and marked sex differences have been described in the course of HIV-1 disease. HIV-1-infected women tend to have lower viral loads early in HIV-1 infection but progress faster to AIDS for a given viral load than men. Here we show substantial sex differences in the response of plasmacytoid dendritic cells (pDCs) to HIV-1. pDCs derived from women produce markedly more interferon-alpha (IFN-alpha) in response to HIV-1-encoded Toll-like receptor 7 (TLR7) ligands than pDCs derived from men, resulting in stronger secondary activation of CD8(+) T cells. In line with these in vitro studies, treatment-naive women chronically infected with HIV-1 had considerably higher levels of CD8(+) T cell activation than men after adjusting for viral load. These data show that sex differences in TLR-mediated activation of pDCs may account for higher immune activation in women compared to men at a given HIV-1 viral load and provide a mechanism by which the same level of viral replication might result in faster HIV-1 disease progression in women compared to men. Modulation of the TLR7 pathway in pDCs may therefore represent a new approach to reduce HIV-1-associated pathology.