Prevalence, incidence and risk factors for pharyngeal chlamydia in the community based Health in Men (HIM) cohort of homosexual men in Sydney, Australia.

OBJECTIVES: To determine the prevalence, incidence and risk factors for pharyngeal Chlamydia trachomatis in the community based Health in Men (HIM) cohort of HIV negative homosexual men in Sydney, Australia. METHODS: From January 2003, all HIM participants were offered annual screening for pharyngeal chlamydia using BD ProbeTec nucleic acid amplification testing (NAAT). Detailed sexual behavioural data were collected every 6 months, and risk factors for infection and hazard ratios were calculated using Cox regression. RESULTS: Among 1427 participants enrolled, the prevalence of pharyngeal chlamydia on initial testing was 1.06% and the incidence rate was 0.58 per 100 person-years. More than 50% of all infections were identified on baseline testing and 68% of men with pharyngeal infection had no evidence of concurrent anogenital chlamydia. There was no association of pharyngeal chlamydia with sore throat. Infection was significantly associated with increasing frequency of receptive penile-oral sex with ejaculation with casual partners (p = 0.009), although approximately half of infections occurred in participants not reporting this risk behaviour. Neither kissing nor oro-anal practices were associated with infection. CONCLUSION: The incidence of pharyngeal chlamydia infection in the HIM study was relatively low; however, the relatively high prevalence on baseline testing compared to incidence suggests a long duration of infection. Occasional screening for pharyngeal chlamydia in homosexual men who frequently practise receptive oral sex with ejaculation may be warranted.

Incidence and risk factors for urethral and anal gonorrhoea and chlamydia in a cohort of HIV-negative homosexual men: the Health in Men Study.

BACKGROUND: Early detection and treatment of bacterial sexually transmitted infections has been advocated as an HIV prevention strategy. AIM: To inform screening guidelines, the incidence and risk factors for urethral and anal gonorrhoea and chlamydia were studied in a prospective cohort of community-based HIV negative homosexual men in Sydney, New South Wales, Australia. METHODS: All participants were offered annual screening for gonorrhoea and chlamydia (study-visit diagnoses) on urine and anal swabs using nucleic acid amplification. Participants also reported diagnoses of gonorrhoea and chlamydia made elsewhere between interviews (interval diagnoses). All diagnoses were summed to create a combined incidence rate, and detailed data on specific sexual practices with casual and regular partners were collected. RESULTS: Among 1427 men enrolled, the combined incidence rates were 3.49 and 2.96 per 100 person-years for urethral and anal gonorrhoea, respectively; and 7.43 and 4.98 per 100 person-years for urethral and anal chlamydia, respectively. Urethral infections were associated with unprotected anal intercourse (UAI) with HIV-positive partners (hazard ratio (HR) = 2.58, 95% CI 1.10 to 6.05 for urethral gonorrhoea) and with frequent insertive oral sex (p for trend 0.007 for urethral chlamydia). Anal infections were associated with receptive UAI (p for trend 0.001 for both anal gonorrhoea and chlamydia) and other receptive anal sexual practices. Stratified analyses showed the independence of the associations of insertive oral sex with urethral infections and of non-intercourse receptive anal practices with anal infections. CONCLUSION: Incident gonorrhoea and chlamydia were common. Risk behaviours for both urethral and anal infections were not restricted to UAI. Screening that includes tests for anal and urethral infections should be considered for all sexually active homosexual men, not just for those who report UAI.

Increased turnover of CCR5+ and redistribution of CCR5- CD4 T lymphocytes during primary human immunodeficiency virus type 1 infection.

CCR5 is the major coreceptor for human immunodeficiency virus (HIV) type 1 during primary infection. CCR5+ CD4 T lymphocytes were studied in subjects with primary HIV-1 infection (PHI) or acute Epstein-Barr virus (EBV) infection and in HIV-uninfected controls. The early decline of CD4 T lymphocytes during PHI resulted from depletion of CCR5- CD4 T lymphocytes. After antiretroviral therapy, Ki-67- CCR5- CD4 T cell counts rapidly increased in the circulation, which suggests that the initial decrease was due to an alteration in trafficking and/or sequestration. In the CCR5+ subset of CD4 T cells, there was an elevation in the proliferative (Ki-67+) fraction during PHI, yet their total number remained in the normal range. In contrast, in acute EBV infection, proliferating CCR5+ CD4 T cells accumulated to very high levels, suggesting they have an important role in the early antiviral response, which may be impaired in HIV-1 infection.

Evidence for independent development of resistance to HIV-1 reverse transcriptase inhibitors in the cerebrospinal fluid.

OBJECTIVES: To delineate and compare the nature and frequency of mutations known to confer resistance to HIV-1 nucleoside reverse transcriptase inhibitors in the cerebrospinal fluid (CSF) and blood compartments. METHODS: Fifty-three paired CSF and plasma specimens had been prospectively collected and stored from 49 HIV-1 infected patients. These were tested using a commercially available line probe assay which allows the simultaneous detection of wild-type and drug selected variants conferring resistance to one or more drugs: zidovudine, didanosine, zalcitabine, and lamivudine. RESULTS: Of the 53 (58%) paired samples, 31 could be amplified by nested PCR. The current assay's limitation for use with CSF is highlighted as 91% of blood samples amplified compared with 60% of CSF samples showing the assays inability to amplify viral loads below 1000 copies/ml. Of the 31 patients 21 (68%) had identical resistance patterns in the CSF and plasma; the other 10 (32%) patients had a resistance profile in the CSF that was different from that in their plasma. Of these, three samples demonstrated amino acid changes associated with high level zidovudine resistance in the CSF but the blood sample remained genotypically sensitive. Nine samples demonstrated resistance in blood but remained wild-type in the CSF. Resistant genotypes were detected in CSF for all nucleosides except didanosine. CONCLUSIONS: Differences in the positions and frequencies of wild-type and drug selected variants in specimens derived from the CSF and blood compartments were detected in a significant number of patients; this argues for the independent development of drug resistance in the CNS in some patients. These findings may have important implications in guiding antiretroviral therapy in HIV-1 infection.

Hepatitis C virus antibody prevalence among injecting drug users at selected needle and syringe programs in Australia, 1995-1997. Collaboration of Australian NSPs.

OBJECTIVES: To describe point prevalence of HCV antibody and relevant risk behaviour among people who inject drugs and who attended selected needle and syringe programs throughout Australia in 1995, 1996 and 1997. DESIGN AND SETTING: Repeated cross-sectional surveys of one week's duration were carried out in 21, 20 and 23 needle and syringe program sites throughout Australia in 1995, 1996 and 1997, respectively. PARTICIPANTS: All clients attending participating sites during the designated survey week were asked to complete a self-administered questionnaire and provide a finger-prick blood sample for HCV antibody testing. MAIN OUTCOME MEASURES: Prevalence of HCV antibody. RESULTS: Survey response was 41% (n = 979) in 1995, 51% (n = 1463) in 1996 and 48% (n = 1699) in 1997. HCV prevalence declined significantly from 63% in 1995 to 51% in 1996 and 50% in 1997 (P < 0.001). Among respondents who reported injecting for less than three years, prevalence declined from 22% in 1995 to 13% in 1996 and 1997 (P < 0.001). Reported use of needles and syringes after someone else in the previous month declined from 31% in 1995 and 28% in 1996 to 15% in 1997 (P < 0.001). CONCLUSIONS: Despite an apparent decline in HCV prevalence, carriage rates of HCV antibody remain high.

Potent antiretroviral therapy of primary human immunodeficiency virus type 1 (HIV-1) infection: partial normalization of T lymphocyte subsets and limited reduction of HIV-1 DNA despite clearance of plasma viremia.

Antiretroviral therapy commenced during primary human immunodeficiency virus type 1 (HIV-1) infection (PHI) may limit the extent of viral replication and prevent early loss of HIV-specific CD4 lymphocyte function. We studied the effect of current standard therapy (2 nucleoside analogues and a protease inhibitor) in 16 patients with symptomatic PHI. In the 13 patients who completed 1 year of treatment, plasma HIV RNA was <50 copies/mL and median CD4 cell counts were comparable to HIV-uninfected controls, with naive (CD45RA+CD62L+), primed (CD45RO+), and T cell receptor Vbeta subsets all within normal ranges. However, HIV-1 DNA levels in treated and untreated PHI patients were similar. Furthermore, CD8 cell counts remained elevated, including activated (CD38+HLA-DR+), replicating (Ki-67+), and cytotoxic (perforin+CD28-) lymphocytes. In conclusion, early antiretroviral therapy resulted in clearance of viremia and prevented loss of crucial CD4 subsets. The persistence of HIV-1 DNA together with increased CD8 T lymphocyte turnover and activation indicate continued expression of viral antigens.

Predictors of progression in long-term nonprogressors. Australian Long-Term Nonprogressor Study Group.

It is now apparent that a proportion of individuals (5-8%) remains clinically free of HIV-1 disease with normal levels of CD4+ lymphocytes (> or =500/microl) for more than 8 years following infection. However, the proportion of these individuals who ultimately progress to AIDS remains to be established. We determined the virological and immunological characteristics of a cohort of long-term nonprogressors in Australia and examined the role of these factors in predicting disease progression. Individuals with documented asymptomatic HIV-1 infection for at least 8 years with CD4+ lymphocyte counts >500 cells/microl were recruited from hospital clinics and general practices serving the eastern area of Australia. CD4+ lymphocyte count, rate of CD4+ lymphocyte change, CD8+ lymphocyte count, beta2-microglobulin, immune complex dissociated (ICD) HIV-1 p24 antigen, and plasma HIV-1 RNA were measured at baseline and multiple visits at 6-month intervals over an average period of 2 years. Up to November 1996, 67 study participants were recruited, of whom 72% had been infected with HIV-1 for at least 10 years. HIV-1 RNA correlated with beta2-microglobulin, ICD p24 antigen, and the ability to isolate virus in culture but not with levels of CD4+ or CD8+ lymphocytes. Serum beta2-microglobulin was a stronger predictor of CD4+ lymphocyte decline than HIV-1 RNA and the only factor significantly associated with CD4+ lymphocyte decline. These findings show that the serum concentration of beta2-microglobulin is a strong predictor of immunological progression in people with long-term asymptomatic HIV-1 infection and provides additional prognostic information to HIV-1 RNA in determining the risk of disease progression.

HIV prevalence and risk behaviour in needle exchange attenders: a national study. The Collaboration of Australian Needle Exchanges.

OBJECTIVE: To determine whether needle and syringe exchange programs represent feasible sites to describe the prevalence of HIV and related risk behaviour among injecting drug users. DESIGN: Cross-sectional survey. SETTING: 21 needle and syringe exchange programs in all Australian jurisdictions. PARTICIPANTS: All persons attending the needle and syringe exchange programs over one week in March 1995 were eligible to participate in the study once. INTERVENTION: Needle and syringe exchange attenders were asked to complete a brief, self-administered questionnaire and provide a finger-prick blood sample. MAIN OUTCOME MEASURES: Prevalence of HIV antibody, drug injecting and sexual behaviour, and survey cost. RESULTS: Completed questionnaires with blood samples suitable for testing were provided by 1005 (42%) of 2373 individuals who attended the needle and syringe exchange programs during the survey week. Women were more likely than men to participate in the survey but there was no difference in the response rate by age group. The HIV prevalence was 2.1% and was significantly higher in men who described themselves as homosexual, compared to men who described themselves as heterosexual (22.5% v. 0.7%; P < 0.001). Thirty-one per cent of respondents reported using a syringe after someone else in the preceding month. CONCLUSION: Cross-sectional surveys of needle exchange clients offer a practical method for monitoring risk behaviour and seroprevalence of bloodborne viral infections.

L-Histidine tetrafluoroborate: a solution-grown semiorganic crystal for nonlinear frequency conversion.

The crystal structure, refractive indices, and phase-matching conditions for a new nonlinear optical material, L-histidine tetrafluoroborate (HFB), are reported. HFB grows readily, displays favorable mechanical characteristics, and has adequate birefringence to permit phase-matched parametric processes over much of its transparency range (250 nm to 1300 nm). The phase-matching loci and angular sensitivity for second-harmonic generation of 1064-nm light in single crystals of HFB were measured. The effective nonlinearity for HFB is comparable with that of beta-barium borate (~2 pm/V), and its angular sensitivity [delta(Deltak)/deltatheta] is somewhat smaller.

Prevalence of maternal HIV infection based on anonymous testing of neonates, Sydney 1989.

The presence of antibody to human immunodeficiency virus (HIV) in post-partum women may be inferred by screening the blood of their newborn babies, since maternal IgG antibodies freely cross the placenta. We tested a sample of 10,217 newborns from 10 hospitals covering three areas in Sydney and other metropolitan centres in New South Wales from April to July, 1989. None of the specimens gave a positive test for antibody to HIV. Thus, the prevalence of HIV positive serology in this sample of newborns was found to be zero. It was estimated that the seroprevalence of antibody to HIV among all neonates in the study area was between zero and 0.045% (99% confidence interval). Because newborns are an accessible group for the study of HIV, and can act as surrogates for their mothers, anonymous testing of this sentinel group will remove some of the limitations generalizing the information in the present database of HIV infection in Australia. This study provides baseline data and suggests that there is not a widespread epidemic of HIV infection among heterosexual persons in Australia at the present time and that routine antenatal testing of women for antibody to HIV may not be cost-effective. However, it will be important to repeat this study at regular intervals to detect any increase in HIV seroprevalence.

Rheumatoid vasculitis: effect of cyclophosphamide on the clinical course and levels of circulating immune complexes.

A study of five patients with severe rheumatoid vasculitis treated with cyclophosphamide was undertaken to determine whether immune complexes were present in serum and if their levels correlated with disease activity and response to treatment. Circulating immune complexes were measured by various techniques including the Clq binding and Raji cell radioimmunoassays and determination of the presence of cryoglobulins. Elevated levels of circulating immune complexes, hypocomplementemia, and high titer rheumatoid factor were present during active vasculitis. Clinical and serologic remissions were induced in all patients on cyclophosphamide. In two patients in remission, a rise in rheumatoid factor titer and immune complex levels was associated with an exacerbation of vasculitis and resolved on increased cyclophosphamide dosage. The Clq binding assay and rheumatoid factor titer correlated best with clinical activity. Thus, circulating immune complexes appear to be involved in the immunopathogenesis of rheumatoid vasculitis, which can be successfully treated with cyclophosphamide.

Scleroderma: developments from Osler to the present.

The clinical entity of progressive systemic sclerosis (PSS, or scleroderma) has remained unchanged since Osler's first description in 1892. Several related or overlap syndromes have now been recognized, which may afford some insight into etiologic events in the development of PSS. As yet, the cause of PSS remains elusive. Abnormalities of collagen synthesis, the role of cellular and humoral immunity, and the relationship of these to vascular disease and hyperreactivity represent current areas of research. Few therapeutic advances of proven efficacy have been forthcoming over this period except for the use of vigorous antihypertensive therapy or early nephrectomy, dialysis, and transplantation in the control of malignant hypertension and progressive renal failure.

Immune complexes in progressive systemic sclerosis and mixed connective tissue disease.

Sera from patients with progressive systemic sclerosis (PSS) and mixed connective tissue disease (MCTD) were studied for the presence of circulating immune complexes (CICs) by Clq precipitins, cryoglobulins and the Raji cell and Clq radioimmunoassays. The Raji cell assay was the most sensitive, detecting ICs in 82% of patients with MCTD and in 55% with PSS. However, the median value in MCTD was significantly higher than in PSS (79 vs 20 microgram equivalent AHG/ml serum), and in MCTD, unlike PSS, the CIC levels appeared to parallel disease activity. Ribonucleoprotein (RNP) antigen could not be demonstrated in the Raji cell bound complexes.