HIV immune escape at an immunodominant epitope in HLA-B*27-positive individuals predicts viral load outcome.

The CTL response in HLA-B*27(+) HIV-infected individuals is characterized by an immunodominant response to a conserved epitope in gag p24 (aa 263-272, KRWIILGLNK; KK10). Mutations resulting in substitution of the arginine (R264) at position 2 of this epitope have been identified as escape mutations. Nineteen HLA-B*27(+) long-term nonprogressors were identified from an Australian cohort with an average follow-up of 16 y following infection. Viral and host genetic factors impacting on disease progression were determined at multiple time points. Twelve of 19 had wild-type sequences at codon 264 at all time points; 7 of 19 carried CTL escape variants. Median viral load and CD4(+) T cell counts were not significantly different between these groups at enrollment. Viral load, as judged by levels at their last visit (1,700 and 21,000 RNA copies/ml, respectively; p = 0.01) or by time-weighted area under the curve was higher in the escape group (p = 0.02). Escape mutants at other HLA-B*27-restricted epitopes were uncommon. Moreover, host polymorphisms, such as CCR5Δ32, CCR2-64I, and SDF1-3'A, or breadth of TCR repertoire responding to KK10 did not segregate to wild-type or escape groups. Host and viral factors were examined for a relationship to viral load. The only factor to affect viral load was the presence of the R264 escape mutations at the immunodominant epitope. CTL escape at R264 in the KK10 epitope is a major determinant of subsequent viral load in these HLA-B*27(+) individuals.

Epidemiology of syphilis in Australia: moving toward elimination of infectious syphilis from remote Aboriginal and Torres Strait Islander communities?

OBJECTIVE: To describe the epidemiology of infectious syphilis among Aboriginal and Torres Strait Islander (Indigenous) people in Australia. DESIGN AND SETTING: We assessed trends in national infectious syphilis notification rates from 2005 to 2009 using Poisson regression, with a focus on geographic and demographic differences by Indigenous status. We compared Indigenous and non-Indigenous rate ratios over the study period and summarised the annual changes (summary rate ratio). MAIN OUTCOME MEASURES: Crude notification rates and summary rate ratios by Indigenous status, jurisdiction, sex, age group and area of residence. RESULTS: From 2005 to 2009, in the Indigenous population, there was a substantial decline in the notification rate for infectious syphilis nationally; as well as in the following subgroups: females, 15-29 year olds, and people living in outer regional and remote areas in the Northern Territory and Queensland. In contrast, there was a significant (P < 0.001) upward trend in the notification rate in the non-Indigenous population nationally; as well as in males, in people aged 20 years and over, and in residents of metropolitan and regional areas, New South Wales, Queensland, South Australia, Victoria and Western Australia. The highest summary rate ratios were seen in remote/very remote areas (86.33; 95% CI, 57.45-129.74), in 15-19 year olds (64.65; 95% CI, 51.12-81.78), in females (24.59; 95% CI, 19.73-30.65), and in Western Australia (23.89; 95% CI, 19.82-28.82). CONCLUSION: These data demonstrate that Australia has two distinct patterns of infectious syphilis: a substantially declining occurrence in Indigenous remote communities and an increasing incidence in males residing in urban and regional areas. Given the decline in notification rates in Indigenous remote communities, now might be the right time to move toward eliminating infectious syphilis from Indigenous communities.

Continuing declines in some but not all HIV-associated cancers in Australia after widespread use of antiretroviral therapy.

OBJECTIVE: To describe changes in cancer incidence in people with HIV in Australia since the introduction of highly active antiretroviral therapy (HAART). DESIGN: Population-based, retrospective cohort study of people with HIV (n = 20 232) using data linkage between national registers of HIV/AIDS and cancer in 1982-2004. METHODS: Age-adjusted and sex-adjusted incidence rate ratios with 95% confidence intervals were calculated to compare site-specific cancer incidence during the early (1996-1999) and late (2000-2004) HAART periods with that prior to HAART (1982-1995). Five-year age-specific, sex-specific, calendar year-specific, and state-specific standardized incidence ratios with 95% confidence interval were also calculated for each period. RESULTS: Incidence of Kaposi sarcoma and non-Hodgkin lymphoma declined significantly (Ptrend < 0.001). Incidence of Hodgkin lymphoma was significantly higher during the early-HAART period (incidence rate ratio 2.34, 95% confidence interval 1.19-4.63) but declined thereafter (Pdiff = 0.014). Incidence of anal cancer was unchanged (Ptrend = 0.451) and remained raised more than 30-fold. Incidence declined significantly for melanoma (Ptrend = 0.041) and prostate cancer (Ptrend = 0.026), and, during the late-HAART period, was lower than in the general population for both cancers. Incidence of colorectal cancer was consistently lower than in the general population. CONCLUSION: Incidence of Kaposi sarcoma and non-Hodgkin lymphoma has continued to decline among people with HIV in Australia, though it remains very substantially elevated. Incidence of Hodgkin lymphoma may now also be declining. Incidence of anal cancer has remained stable, and it is now the third most common cancer in HIV-infected Australians. Reasons for the reduced incidence of colorectal and prostate cancer, and more recently of melanoma, are unclear.

Could sexually transmissible infections be contributing to the increase in HIV infections among men who have sex with men in Australia?

BACKGROUND: To review existing data on sexually transmissible infections (STI) in men who have sex with men in Australia in order to determine the possible contribution of STI to diverging trends in HIV notifications in different states. METHODS: We reviewed data from multiple sources, including routine national surveillance data, laboratory surveillance data, self-reported information on STI testing in men who have sex with men and ad hoc reports of STI prevalence. RESULTS: We found increasing rates of gonorrhoea and infectious syphilis notifications in urban men in Australia between 1997 and 2006, and increasing rates of chlamydia notifications in men aged 30-49 years. There was little difference in these trends by state. Differences in the population groups sampled meant we were unable to gain further information on trends in men who have sex with men from these studies. Data on STI testing showed an increase in anal STI testing between 2003 and 2006, which may have increased the number of diagnoses of chlamydia and gonorrhoea for men who have sex with men during this period. CONCLUSIONS: Over the past 10 years, there has been a substantial increase in diagnoses of gonorrhoea and infectious syphilis, and probably chlamydia, in men who have sex with men in Australia. However, it is unlikely that changes in the pattern of STI transmission are responsible for the recent divergence in HIV rates between Australian states because there is little evidence that trends in STI also differ by state.