Subtype-specific differences in transmission cluster dynamics of HIV-1 B and CRF01_AE in New South Wales, Australia

Introduction: The human immunodeficiency virus 1 (HIV-1) pandemic is characterized by numerous distinct sub-epidemics (clusters) that continually fuel local transmission. The aims of this study were to identify active growing clusters, to understand which factors most influence the transmission dynamics, how these vary between different subtypes and how this information might contribute to effective public health responses. Methods: We used HIV-1 genomic sequence data linked to demographic factors that accounted for approximately 70% of all new HIV-1 notifications in New South Wales (NSW). We assessed differences in transmission cluster dynamics between subtype B and circulating recombinant form 01_AE (CRF01_AE). Separate phylogenetic trees were estimated using 2919 subtype B and 473 CRF01_AE sequences sampled between 2004 and 2018 in combination with global sequence data and NSW-specific clades were classified as clusters, pairs or singletons. Significant differences in demographics between subtypes were assessed with Chi-Square statistics. Results: We identified 104 subtype B and 11 CRF01_AE growing clusters containing a maximum of 29 and 11 sequences for subtype B and CRF01_AE respectively. We observed a > 2-fold increase in the number of NSW-specific CRF01_AE clades over time. Subtype B clusters were associated with individuals reporting men who have sex with men (MSM) as their transmission risk factor, being born in Australia, and being diagnosed during the early stage of infection (p 1.5 sequences / 6-months) and which consisted of a majority of infections among MSM. We also found four active growing CRF01_AE clusters containing only infections among MSM. Finally, we found 47 subtype B and seven CRF01_AE clusters that contained a large gap in time (>1 year) between infections and may be indicative of intermediate transmissions via undiagnosed individuals. Conclusions: The large number of active and growing clusters among MSM are the driving force of the ongoing epidemic in NSW for subtype B and CRF01_AE.Francesca Di Giallonardo, Angie N Pinto, Phillip Keen, Ansari Shaik, Alex Carrera, Hanan Salem, Christine Selvey, Steven J Nigro, Neil Fraser, Karen Price, Joanne Holden, Frederick J Lee, Dominic E Dwyer, Benjamin R Bavinton, Jemma L Geoghegan, Andrew E Grulich, Anthony D Kelleher, NSW HIV Prevention Partnership Project ... Mark Boyd ... et al

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

Cancer, immunodeficiency and antiretroviral treatment: Results from the Australian HIV Observational Database (AHOD)

The objective of the study was to conduct a within-cohort assessment of risk factors for incident AIDS-defining cancers (ADCs) and non-ADCs (NADCs) within the Australian HIV Observational Database (AHOD).A total of 2181 AHOD registrants were linked to the National AIDS Registry/National HIV Database (NAR/NHD) and the Australian Cancer Registry to identify those with a notified cancer diagnosis. Included in the current analyses were cancers diagnosed after HIV infection. Risk factors for cancers were also assessed using logistic regression methods.One hundred and thirty-nine cancer cases were diagnosed after HIV infection among 129 patients. More than half the diagnoses (n = 68; 60%) were ADCs, of which 69% were Kaposi's sarcoma and 31% non-Hodgkin's lymphoma. Among the NADCs, the most common cancers were melanoma (n = 10), lung cancer (n = 6), Hodgkin's lymphoma (n = 5) and anal cancer (n = 5). Over a total of 21021 person-years (PY) of follow-up since HIV diagnosis, the overall crude cancer incidence rate for any cancer was 5.09/1000 PY. The overall rate of cancers decreased from 15.9/1000 PY [95% confidence interval (CI) 9.25-25.40/1000 PY] for CD4 counts 350 cells/μL. Lower CD4 cell count and prior AIDS diagnoses were significant predictors for both ADCs and NADCs.ADCs remain the predominant cancers in this population, although NADC rates have increased in the more recent time period. Immune deficiency is a risk factor for both ADCs and NADCs

Hepatitis C transmission and HIV post-exposure prophylaxis after needle- and syringe-sharing in Australian prisons

Objectives: To determine whether infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) occurred after two potential episodes of exposure through needle- and syringe-sharing in Australian prisons, and to examine use of post-exposure prophylaxis (PEP) against HIV infection in the prison setting. Design: Cohort study of potential contacts of two prisoners infected with HIV, HBV and HCV followed up for up to 14 months. Setting: Two Australian prisons between November 2000 (time of exposure) and December 2001. Participants: Two index patients (both infected with HIV and HCV; one also infectious for HBV) from two different prisons, and 104 inmates who shared needles and syringes. Main outcome measures: Seroconversions to HIV, HBV and HCV related to the high-risk exposure and uptake and completion of HIV PEP determined from medical records of inmates. Results: There were four seroconversions to HCV within 14 months of the potential exposure (14% of those susceptible in the cohort), but no recorded HIV or HBV seroconversions. Forty-six inmates (82% of those eligible) were offered PEP, and 34 of these (74%) elected to receive it. Only eight (24% of the 34) completed the full PEP course. Conclusions: HCV transmission in the prison setting is related to high-risk needle- and syringe-sharing. Administering HIV PEP in the prison setting is complicated by challenging risk assessment and follow-up

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

Objective: To explore trend 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 150x106/l (P = 0.02). A decline in median CD4 T-lymphocyte count at KS diagnosis was seen, from 67x106/l in 1984-1987 to 20x106/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

Specific infections, infection-related behavior, and risk of non-Hodgkin lymphoma in adults

Infections were examined as possible risk factors for non-Hodgkin lymphoma in a population-based case-control study in New South Wales and the Australian Capital Territory, Australia. Incident cases (n = 694) had no history of HIV infection or transplantation. Controls (n = 694) were randomly selected from electoral rolls and frequency matched to cases by age, sex, and area of residence. A postal questionnaire and telephone interview measured history of specific infections, occupational exposures, and behavioral and other risk factors for infection. Blood samples were tested for antibodies to human T-lymphotrophic virus type I and hepatitis C virus. Logistic regression models included the three matching variables and ethnicity. There was no association between risk of non-Hodgkin lymphoma and any of the variables analyzed, including sexually transmitted infections, sexual behavior, blood transfusions, influenza, acne, and either occupational or domestic exposure to zoonotic infections. Non-Hodgkin lymphoma risk was nonsignificantly elevated (odds ratio, 2.99; 95% confidence interval, 0.78-11.51) for those with a history of injecting drug use. Three cases and two controls (odds ratio, 1.32; 95% confidence interval, 0.22-7.98) tested positive to hepatitis C virus infection and none tested positive to human T-lymphotrophic virus type I/II infection. This study provides consistent evidence that sexually transmitted infections and zoonoses are not risk factors for non-Hodgkin lymphoma

Sun exposure may protect against non-Hodgkin lymphoma: a case-control study

Ultraviolet radiation is a hypothesised risk factor for non-Hodgkin lymphoma (NHL) but no epidemiological study has examined this association using direct measures of sun exposure in individuals. Adults aged 20-74 years living in NSW and ACT, Australia, were the study population. Cases (704 of 829 invited to take part, 85%) were diagnosed January 2000 to August 2001. Controls (694 of 1,136 invited to take part, 61%) were randomly selected from state electoral rolls and frequency-matched to cases by age, sex and state of residence. A self-administered questionnaire and telephone interview measured outdoor hours on working and nonworking days and vacations at 10, 20, 30, 40, 50 and 60 years of age. Logistic regression models of NHL and sun exposure contained the 3 matching variables, ethnicity and sun sensitivity measures as covariates. Contrary to expectations, risk of NHL fell with increasing reported sun exposure hours. Relative to 1.0 for the lowest quarter of total sun exposure hours, the odds ratios (ORs) for successively higher quarters were 0.72 (95% CI 0.53-0.98), 0.66 (0.48-0.91) and 0.65 (0.46-0.91) (ptrend=0.01). The association of sun exposure on nonworking days with NHL was stronger; OR for highest quarter 0.47 (0.34-0.66) (ptrend=0.0001). Risk also fell with sun exposure on vacations; OR for highest quarter 0.60 (0.43-0.85) (ptrend=0.003). These associations appeared strongest in women and in childhood. There was little evident trend in risk with exposure on working day. Our results provide strong statistical evidence for an inverse association between sun exposure and NHL. Increasing evidence that vitamin D may protect against cancer makes UV-mediated synthesis of vitamin D a plausible mechanism whereby sun exposure might protect agains

Increased targeted HIV testing and reduced undiagnosed HIV infections among gay and bisexual men

Objectives To evaluate the impact of government HIV strategies that aimed to increase HIV testing uptake and frequency among gay and bisexual men (GBM) in New South Wales (NSW), Australia. Design We analysed HIV testing data from existing passive and sentinel surveillance systems between 2010 and 2018. Methods Six indicators were measured: (1) state-wide total HIV laboratory tests; (2) number of GBM attending publicly-funded clinics; (3) 12-monthly testing uptake; (4) annual testing frequency; (5) HIV testing with a STI diagnosis; and (6) HIV positivity. Mathematical modelling was used to estimate (7) the proportion of men with undiagnosed HIV. Indicators were stratified by Australian vs. overseas-born. Results Overall, 43,560 GBM attended participating clinics (22,662 Australian-born, 20,834 overseas-born) from 2010-2018. Attendees increased from 5,186 in 2010 to 16,507 in 2018. There were increasing trends (p<0.001 for all) in testing uptake (83.9% to 95.1%); testing with a STI diagnosis (68.7% to 94.0%); annual HIV testing frequency (1.4 to 2.7); and a decreasing trend (p<0.01) in HIV positivity (1.7% to 0.9%).Increases in testing were similar in Australian-born and overseas-born GBM. However, there were decreasing trends in the estimated undiagnosed HIV proportion overall (9.5% to 7.7%) and in Australian-born GBM (7.1% to 2.8%), but an increasing trend in overseas-born GBM (15.3% to 16.9%) (p<0.001 for all).PG Patel, P Keen, H McManus, T Duck, D Callander, C Selvey ... et al