A longitudinal cohort study of HIV 'treatment as prevention' in gay, bisexual and other men who have sex with men: the Treatment with Antiretrovirals and their Impact on Positive And Negative men (TAIPAN) study protocol.

BACKGROUND: Australia has increased coverage of antiretroviral treatment (ART) over the past decade, reaching 73% uptake in 2014. While ART reduces AIDS-related deaths, accumulating evidence suggests that it could also bolster prevention efforts by reducing the risk of HIV transmission ('treatment as prevention'). While promising, evidence of community-level impact of treatment as prevention on reducing HIV incidence among gay and bisexual men is limited. We describe a study protocol that aims to determine if scale up of testing and treatment for HIV leads to a reduction in community viraemia and, in turn, if this reduction is temporally associated with a reduction in HIV incidence among gay and bisexual men in Australia's two most populous states. METHODS: Over the period 2009 to 2017, we will establish two cohorts making use of clinical and laboratory data electronically extracted retrospectively and prospectively from 73 health services and laboratories in the states of New South Wales and Victoria. The 'positive cohort' will consist of approximately 13,000 gay and bisexual men (>90% of all people living with HIV). The 'negative cohort' will consist of at least 40,000 HIV-negative gay and bisexual men (approximately half of the total population). Within the negative cohort we will use standard repeat-testing methods to calculate annual HIV incidence. Community prevalence of viraemia will be defined as the proportion of men with a viral load ≥200RNA copies/mm3, which will combine viral load data from the positive cohort and viraemia estimates among those with an undiagnosed HIV infection. Using regression analyses and adjusting for behavioural and demographic factors associated with infection, we will assess the temporal association between the community prevalence of viraemia and the incidence of HIV infection. Further analyses will make use of these cohorts to assess incidence and predictors of treatment initiation, repeat HIV testing, and viral suppression. DISCUSSION: This study will provide important information on whether 'treatment as prevention' is associated with a reduction in HIV incidence at a community level among gay and bisexual men.

Non-occupational post-exposure prophylaxis in Victoria, Australia: responding to high rates of re-presentation and low rates of follow-up.

In Australia, the non-occupational post-exposure prophylaxis service in Victoria (VNPEPS) maintains a database of non-occupational post-exposure prophylaxis (NPEP) use throughout the state. Through the database the service can monitor and respond to patterns of NPEP presentation, re-presentation and follow-up as well as those who test positive for HIV. We describe a cohort of NPEP individuals from the commencement of the service to 31 December 2009. During this time, 1864 individuals presented for NPEP on 2396 occasions. The majority (85%) were men who have sex with men (MSM) presenting after receptive anal intercourse (56.1%). Repeat NPEP presentations were high (17.5%) and follow-up testing at week 12 post-NPEP was low (34%). Twenty-two patients (1.2%) tested positive for HIV at baseline presentation and six patients seroconverted to HIV during follow-up. The VNPEPS has initiated strategies to encourage behaviour change for those who re-present for NPEP, and to improve rates of week 12 follow-up.

Prognosis of Kaposi's sarcoma as an initial and later AIDS associated illness.

BACKGROUND: The natural history of Kaposi's sarcoma (KS) as a primary presentation of AIDS has been well defined, but little is known about the prognosis of KS following a different AIDS defining illness (ADI). PATIENTS AND METHODS: Retrospective review of 852 consecutive individuals diagnosed with AIDS at Fairfield Hospital between 1984 and 1994. Demographic data, year of diagnosis, CD4 cell counts, treatment for KS and PCP prophylaxis were included in the analysis. Survival following a diagnosis of KS was evaluated, adjusting for the effects of year of diagnosis, primary or secondary KS and degree of immunodeficiency. RESULTS: The overall cumulative incidence of KS by three years post ADI was 34%. Median survival for KS as an ADI (n = 130) was 20 months versus 9 months for KS subsequent to another ADI (n = 75, P < 0.001). Those with KS as an ADI had a higher CD4 count (median 90 vs. 11, P < 0.001), lower incidence of visceral disease (5 of 130 vs. 11 of 75, P = 0.032) and fewer associated AIDS related illnesses (1 vs. 2, P < 0.001). Poorer survival following diagnosis of KS was associated with a lower CD4 count at diagnosis of KS (P = 0.002), extensive cutaneous or visceral KS at diagnosis (P = 0.009 and P < 0.001 respectively) and with the number of associated AIDS related illnesses (P < 0.001). A multivariate analysis suggested that, after adjusting for these factors, there was no difference in survival between primary and secondary KS. CONCLUSION: We found no difference in survival between primary and secondary KS after adjusting for potential confounding factors. We cannot exclude, however, that the greater incidence of visceral disease identified in secondary KS reflects an inherently more aggressive biology.

Trends in incidence of AIDS illnesses in Australia from 1983 to 1994: the Australian AIDS cohort.

To assess time trends in incidence of AIDS illnesses in Australia, a retrospective cohort of people diagnosed with AIDS from January 1, 1983 to December 31, 1994 in three HIV medicine units in Sydney, Melbourne, and Perth was established. Data on initial and subsequent AIDS illnesses were available for 2580 AIDS cases, or 45% of Australian AIDS notifications over the study period. Males represented 97.2% of the cohort, and HIV exposure category was homosexual contact for 89.9%. Subcohorts were formed by interval of AIDS diagnosis: 1983 through 1987, 1988 through 1990, and 1991 through 1994, with estimation of cumulative risk for each AIDS illness by the Kaplan-Meier method. The cumulative risk declined for Pneumocystis carinii pneumonia (PCP) (p < 0.0001) and for Kaposi's sarcoma (KS) (p < 0.0001); PCP cumulative risk estimates 2 years following AIDS diagnosis were 70% for people diagnosed with AIDS in 1983 through 1987 and 48% in 1991 through 1994, and KS cumulative risk estimates 2 years following AIDS diagnosis were 44% in 1983 through 1987 and 32% in 1991 through 1994. In contrast, cumulative risk increased from 34% to 40% for cytomegalovirus (CMV) disease (p = 0.005), from 47% to 50% for Mycobacterium avium complex (MAC) (p < 0.0001), and from 26% to 33% for esophageal candidiasis (p < 0.0001). Corresponding to this changing spectrum of AIDS illness has been an increase in severity of immunodeficiency at AIDS, with median CD4 cell count declining from 54 cells/mm3 in 1983 through 1987 to 34/mm3 in 1991 through 1994 (p = 0.002).

Declining incidence and later occurrence of Kaposi's sarcoma among persons with AIDS in Australia: the Australian AIDS cohort.

OBJECTIVE: To explore trends in cumulative incidence of Kaposi's sarcoma (KS) and the level of immunodeficiency at KS diagnosis among people with AIDS in Australia. SETTING: Three hospital-based HIV units. STUDY POPULATION: Retrospective cohort of 2580 people diagnosed with AIDS over the period 1983-1994, representing 45% of cases of AIDS in Australia over this period. METHODS: Data including date and CD4 T-lymphocyte count of KS diagnosis was abstracted from medical records. KS occurring as both an initial and subsequent AIDS illness was included. Three subcohorts were defined based on interval of AIDS diagnosis: 1983-1987, 1988-1990, 1991-1994. Cumulative risk estimates for KS development were calculated by the Kaplan-Meier method. RESULTS: KS was diagnosed in 716 people (27.8%), and in 451 (63%) of these as the initial AIDS illness. There was a decline over time in cumulative incidence of KS (P < 0.0005); the cumulative risk of KS at 1 year after AIDS diagnosis declined from 35% for those diagnosed with AIDS during 1983-1987 to 25% for 1991-1994. This decline was not due to a decline in homosexual HIV exposure category, and was independent of CD4 T-lymphocyte count at AIDS. In multivariate analysis independent risk factors for KS development were year of AIDS diagnosis (P = 0.003), male homosexuality (P = 0.003), and CD4 T-lymphocyte count at AIDS greater than 150 x 10(6)/l (P = 0.02). A decline in median CD4 T-lymphocyte count at KS diagnosis was seen, from 67 x 10(6)/l in 1984-1987 to 20 x 10(6)/l for 1991-1994 (P < 0.0005). CONCLUSION: The decline in incidence and later occurrence of KS suggest several hypotheses, including declining prevalence or reduced virulence of a KS cofactor.

Predictive value of CD4 lymphocyte numbers for the development of opportunistic infections and malignancies in HIV-infected persons.

Infection with the human immunodeficiency virus (HIV) results in progressive depletion of the CD4 subset T-lymphocytes and the development of opportunistic infections and certain malignancies. Charts were reviewed for 185 HIV-infected individuals with 265 AIDS-defining illnesses (ADIs) who had T-lymphocyte subset analyses performed within 2 months prior to or 1 month following the diagnosis. Also included were 22 HIV-infected patients with oral candidiasis and 20 with asymptomatic infection. Significant differences in CD4 lymphocyte numbers were observed between the 12 ADIs, oral candidiasis, and asymptomatic infection, allowing them to be grouped into five general categories, based on mean CD4 count: (a) asymptomatic infection, CD4 greater than 500/mm3; (b) oral candidiasis and tuberculosis, range 250-500/mm3; (c) Kaposi's sarcoma, lymphoma, and cryptosporidiosis, range 150-200/mm3; (d) Pneumocystis carinii pneumonitis, disseminated Mycobacterium avium complex, herpes simplex ulceration, toxoplasmosis, cryptococcosis, and esophageal candidiasis, range 75-125/mm3; (e) cytomegalovirus retinitis, less than 50/mm3. Our data concur with clinical impressions and provide a basis for interim treatment and prophylaxis recommendations.

Functional versus phenotypic analysis of T cells in subjects seropositive for the human immunodeficiency virus: a prospective study of in vitro responses to Cryptococcus neoformans.

We performed a prospective study of 50 subjects at high risk for human immunodeficiency virus (HIV) infection to determine if assays of antigen-specific T cell function provide an earlier indication of future progression to AIDS or a better assessment of immune function than do current methods of evaluation. We measured in vitro T cell responses to Cryptococcus neoformans and tetanus toxoid, response to mitogens, HIV p24 antigenemia, and clinical parameters. Progression to AIDS was significantly associated with loss of T cell response to cryptococci (P = .015), HIV antigenemia (P = .001), and low CD4+ cell numbers (P = .001). Most importantly, we found that loss of antigen-specific responses to cryptococci and tetanus can occur before changes in CD4 cell number. Abnormal response to mitogens and marked depletion of CD4+ cells were late signs of progressive HIV infection. Measurement of antigen-specific T cell function may be useful for assessing the efficacy of antiviral therapy in HIV infection before onset of symptoms.

Myogenic and neurogenic regulation of myosin gene expression in cat jaw-closing muscles regenerating in fast and slow limb muscle beds.

Immunocytochemical techniques were used to study changes in myosin gene expression during the regeneration of the cat posterior temporalis muscle transplanted into the bed of either the fast extensor digitorum longus (EDL) or the slow soleus muscle. Strips of the posterior temporalis, a homogeneously superfast muscle, were treated with Marcaine and then transplanted into limb muscle beds which had been completely cleared of host muscle fibres. The regenerates were examined 6 to 224 days after surgery. Early regenerates in both muscle beds reacted with antibodies against the heavy chain of foetal, slow and superfast myosins, but not with antibodies against fast myosin. In the long-term, regenerates innervated by the EDL nerve expressed only superfast myosin whereas in the regenerates innervated by the soleus nerve most fibres expressed only slow myosin and only a few fibres reacted exclusively with the anti-superfast myosin antibody even after 210 days. In contrast, EDL and soleus muscles regenerating in their own beds expressed foetal, slow and fast myosin, but did not express superfast myosin. The isometric contraction times of the various types of regenerates reflected the types of myosin synthesized. It is concluded that jaw and limb muscle cells exist as two distinct allotypes, each having a distinct repertoire for the expression of adult isomyosins, and that within that repertoire isomyosin gene expression can be modulated by the nerve. Thus, myosin gene expression in skeletal muscle fibres is regulated by both myogenic and neurogenic mechanisms.

Mycobacterium fortuitum bacteremia in patients with cancer and long-term venous catheters.

Primary bacteremia due to Mycobacterium fortuitum is an uncommon occurrence. Four cases of M. fortuitum bacteremia in patients with cancer, one of whom was neutropenic, are presented. None of the patients had evidence of disseminated disease or endocarditis, and there was no mortality directly associated with this infection. Two patients had polymicrobial sepsis with skin commensal organisms. The infection was related to the use of long-term central venous catheters or recent instrumentation in all patients. M. fortuitum should be added to the growing list of organisms causing catheter-related infections.

In-vitro activity of Sch 34343, a new penam, against gram-positive isolates from cancer patients.

The in-vitro activity of Sch 34343, a new penam antibiotic, was tested against 257 Gram-positive isolates from cancer patients, and compared with that of imipenem and amifloxacin. Sch 34343 was extremely active against beta-haemolytic streptococci (Lancefield groups A, B and G) with MIC90s ranging from 0.025 to 0.05 mg/l. It was also active against methicillin-susceptible Staphylococcus aureus and had variable activity against coagulase-negative staphylococci. MIC90 for Listeria monocytogenes was 0.78 mg/l and 84% of enterococcal isolates were inhibited by 6.25 mg/l.

In vitro activity of BRL 36650, a new semisynthetic penicillin.

BRL 36650 [sodium 6 beta-(D-2-[(4-ethyl-2, 3-dioxopiperazin-1-yl)carbonylamino]-2-(3,4-dihydroxyphenyl) acetamido)-6 alpha-formamido-penicillinate] is a new semisynthetic penicillin. It was tested in vitro for activity against 884 organisms cultured from blood specimens of cancer patients. BRL 36650 had broad-spectrum activity against the gram-negative bacilli tested but had no gram-positive activity. The MIC against 90% of the Pseudomonas aeruginosa isolates was 3.12 micrograms/ml. The activity of BRL 36650 was superior to that of piperacillin, comparable or slightly inferior to that of aztreonam and ceftazidime, and lower than that of imipenem and amifloxacin. BRL 36650 should prove useful for the management of gram-negative bacillary infections, including those caused by P. aeruginosa.

In vitro activity of SCH-34343, a new penam, and other antimicrobial agents against clinical isolates from cancer patients.

The in vitro activity of SCH-34343, a new penam antibiotic, was tested against gram-positive and gram-negative isolates from cancer patients, and compared to that of 7 other antimicrobial agents. SCH-34343 was extremely active against the Enterobacteriaceae with MIC90 ranging from 0.39 to 6.25 micrograms/ml for Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus spp. and Serratia marcescens. It was less active against Acinetobacter spp. (MIC90 6.25-12.5 micrograms/ml) and had poor activity against Pseudomonas aeruginosa. Among gram-positive isolates group A and G beta-hemolytic Streptococci were extremely susceptible to SCH-34343 (MIC90 0.025-0.05 micrograms/ml). Good activity against methicillin-susceptible coagulase-positive and coagulase-negative Staphylococci and Listeria monocytogenes, and moderate activity against Enterococci was also seen.

Comparative in vitro activity of cefpirome and other antimicrobial agents against isolates from cancer patients.

Cefpirome and six other antimicrobial agents were tested against 884 blood culture isolates from cancer patients. Cefpirome was highly active against aerobic gram-negative bacilli including Acinetobacter spp., and the Enterobacteriaceae. Only imipenem was more active than cefpirome against Pseudomonas aeruginosa. Cefpirome was also extremely active against beta-hemolytic streptococci and methicillin-susceptible staphylococci.