Andrew E. Grulich

Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis

BACKGROUND Only a few types of cancer are recognised as being directly related to immune deficiency in people with HIV/AIDS. Large population-based studies in transplant recipients have shown that a wider range of cancers could be associated with immune deficiency. Our aim was to compare cancer incidence in population-based cohort studies of people with HIV/AIDS and people immunosuppressed after solid organ transplantation. METHODS Two investigators independently identified eligible studies through searches of PubMed and reference lists. Random-effects meta-analyses of log standardised incidence ratios (SIRs) were calculated by type of cancer for both immune deficient populations. FINDINGS Seven studies of people with HIV/AIDS (n=444,172) and five of transplant recipients (n=31 977) were included. For 20 of the 28 types of cancer examined, there was a significantly increased incidence in both populations. Most of these were cancers with a known infectious cause, including all three types of AIDS-defining cancer, all HPV-related cancers, as well as Hodgkins lymphoma (HIV/AIDS meta-analysis SIR 11.03, 95% CI 8.43-14.4; transplant 3.89, 2.42-6.26), liver cancer (HIV/AIDS 5.22, 3.32-8.20; transplant 2.13, 1.16-3.91), and stomach cancer (HIV/AIDS 1.90, 1.53-2.36; transplant 2.04, 1.49-2.79). Most common epithelial cancers did not occur at increased rates. INTERPRETATION The similarity of the pattern of increased risk of cancer in the two populations suggests that it is immune deficiency, rather than other risk factors for cancer, that is responsible for the increased risk. Infection-related cancer will probably become an increasingly important complication of long-term HIV infection.

Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium

Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model. Sjögren syndrome was associated with a 6.5-fold increased risk of NHL, a 1000-fold increased risk of parotid gland marginal zone lymphoma (OR = 996; 95% CI, 216-4596), and with diffuse large B-cell and follicular lymphomas. Systemic lupus erythematosus was associated with a 2.7-fold increased risk of NHL and with diffuse large B-cell and marginal zone lymphomas. Hemolytic anemia was associated with diffuse large B-cell NHL. T-cell NHL risk was increased for patients with celiac disease and psoriasis. Results for rheumatoid arthritis were heterogeneous between studies. Inflammatory bowel disorders, type 1 diabetes, sarcoidosis, pernicious anemia, and multiple sclerosis were not associated with risk of NHL or subtypes. Thus, specific autoimmune disorders are associated with NHL risk beyond the development of rare NHL subtypes in affected organs. The pattern of associations with NHL subtypes may harbor clues to lymphomagenesis.

Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data

BACKGROUND Quadrivalent human papillomavirus (HPV) vaccine has high efficacy in clinical trials but no reports describe its effects at a population level. From July, 2007, Australia was the first country to fund a vaccination programme for all women aged 12-26 years. We established a national surveillance network in Australia and aimed to identify trends in diagnoses of genital warts in 2004-09. METHODS We obtained standardised data for demographic factors, frequency of genital warts, HPV vaccination status, and sexual behaviour for new patients attending eight sexual health services in Australia between January, 2004, and December, 2009. We used χ² analysis to identify significant trends in proportions of patients diagnosed with warts in periods before and after vaccination began. Our primary group of interest was female Australian residents who were eligible for free vaccination, although data were assessed for patients ineligible for free vaccination, including women older than 26 years of age, non-resident women, and men. FINDINGS Among 112 083 new patients attending sexual health services, we identified 9867 (9%) cases of genital warts. Before the vaccine programme started, there was no change in proportion of women or heterosexual men diagnosed with genital warts. After vaccination began, a decline in number of diagnoses of genital warts was noted for young female residents (59%, p(trend)<0·0001). No significant decline was noted in female non-residents, women older than 26 years in July, 2007, or in men who have sex with men. However, proportionally fewer heterosexual men were diagnosed with genital warts during the vaccine period (28%, p(trend)<0·0001), and this effect was more pronounced in young men. By 2009, 65·1% of female Australian residents who were eligible for free vaccine reported receipt of quadrivalent or unknown HPV vaccine. INTERPRETATION The decrease in frequency of genital warts in young Australian women resulting from the high coverage of HPV vaccination might provide protective effects in heterosexual men through herd immunity. FUNDING CSL Biotherapies.

Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data

Objective To measure the effect on genital warts of the national human papillomavirus vaccination programme in Australia, which started in mid-2007. Design Trend analysis of national surveillance data. Setting Data collated from eight sexual health services from 2004 to 2011; the two largest clinics also collected self reported human papillomavirus vaccination status from 2009. Participants Between 2004 and 2011, 85 770 Australian born patients were seen for the first time; 7686 (9.0%) were found to have genital warts. Main outcome measure Rate ratios comparing trends in proportion of new patients diagnosed as having genital warts in the pre-vaccination period (2004 to mid-2007) and vaccination period (mid-2007 to the end of 2011). Results Large declines occurred in the proportions of under 21 year old (92.6%) and 21-30 year old (72.6%) women diagnosed as having genital warts in the vaccination period—from 11.5% in 2007 to 0.85% in 2011 (P<0.001) and from 11.3% in 2007 to 3.1% in 2011 (P<0.001), respectively. No significant decline in wart diagnoses was seen in women over 30 years of age. Significant declines occurred in proportions of under 21 year old (81.8%) and 21-30 year old (51.1%) heterosexual men diagnosed as having genital warts in the vaccination period—from 12.1% in 2007 to 2.2% in 2011 (P<0.001) and from 18.2% in 2007 to 8.9% in 2011 (P<0.001), respectively. No significant decline in genital wart diagnoses was seen in heterosexual men over 30 years of age. In 2011 no genital wart diagnoses were made among 235 women under 21 years of age who reported prior human papillomavirus vaccination. Conclusions The significant declines in the proportion of young women found to have genital warts and the absence of genital warts in vaccinated women in 2011 suggests that the human papillomavirus vaccine has a high efficacy outside of the trial setting. Large declines in diagnoses of genital warts in heterosexual men are probably due to herd immunity.

Relation between HIV viral load and infectiousness: a model-based analysis

BACKGROUND A consensus statement released on behalf of the Swiss Federal Commission for HIV/AIDS suggests that people receiving effective antiretroviral therapy-ie, those with undetectable plasma HIV RNA (<40 copies per mL)-are sexually non-infectious. We analysed the implications of this statement at a population level. METHODS We used a simple mathematical model to estimate the cumulative risk of HIV transmission from effectively treated HIV-infected patients (HIV RNA <10 copies per mL) over a prolonged period. We investigated the risk of unprotected sexual transmission per act and cumulatively over many exposures, within couples initially discordant for HIV status. FINDINGS Assuming that each couple had 100 sexual encounters per year, the cumulative probability of transmission to the serodiscordant partner each year is 0.0022 (uncertainty bounds 0.0008-0.0058) for female-to-male transmission, 0.0043 (0.0016-0.0115) for male-to-female transmission, and 0.043 (0.0159-0.1097) for male-to-male transmission. In a population of 10 000 serodiscordant partnerships, over 10 years the expected number of seroconversions would be 215 (80-564) for female-to-male transmission, 425 (159-1096) for male-to-female transmission, and 3524 (1477-6871) for male-to-male transmission, corresponding to an increase in incidence of four times compared with incidence under current rates of condom use. INTERPRETATION Our analyses suggest that the risk of HIV transmission in heterosexual partnerships in the presence of effective treatment is low but non-zero and that the transmission risk in male homosexual partnerships is high over repeated exposures. If the claim of non-infectiousness in effectively treated patients was widely accepted, and condom use subsequently declined, then there is the potential for substantial increases in HIV incidence. FUNDING Australian Research Council.

In a minority of gay men, sexual risk practice indicates strategic positioning for perceived risk reduction rather than unbridled sex

Abstract The aim of this analysis was to examine gay mens sexual risk practice to determine patterns of risk managemtent. Ten cross-sectional surveys of gay men were condtrcted six-monthly from February 1996 to August 2000 at Sydney gay community social, sex-on-prmises and sexual health sites (average n=827). Evely February during this period, five identical surveys were conducted at the annual Gay and Lesbian Mardi Gras Fair Day (average n=11 78). Among the minority of men who had umprotected and intercourse which involved ejaculation inside with a serodiscordant regular partner, there was a clear pattern of sexual positioning. Few regular couples mere both receptive and insertive. Most HIV-positive men were receptive and insertive. Most HIV-positive men were recptive and most HIV-negative men were insertive. Among the minority of men who had unprotected anal intercourse which involved ejaculation inside with casual partners, there was also a patterns of sexual positioning. Whereas many casual couples were both receptive and insertive (especially those involviug HIV-positive respondents), among the remainder HIV-positive men tended to be receptive and HIV-negative men tended to be insertive. These pattenu of HIV-positive/receptive and HIV-negative/insertive suggest strategic risk reduction positionings rather tlran rrlere sexrial preferences among a minority of gay men. If so, they point they point to complacency but to an ever more cornplex domain of HIV prevention.

The global epidemic of HIV infection among men who have sex with men.

Purpose of reviewIn the last few years, there have been reports of new, newly identified and resurging epidemics of HIV infection among men who have sex with men (MSM). This article reviews and summarizes the global epidemic of HIV infection among MSM. Recent findingsIn the Western world, the increase in notifications of new HIV infections among MSM is continuing. Steep increases in reports of new HIV diagnoses among MSM were also seen in the developed economies of East Asia. In the developing world, epidemiologic studies have now established the presence of MSM populations in Africa, China and Russia and a high HIV prevalence among them. High and increasing HIV prevalence was also reported from South and Southeast Asia, and Latin America and the Caribbean. SummaryHIV continues to spread among MSM on a global level. Current prevention efforts have been unable to contain or reduce HIV transmission in this population. Additional behavioral and biomedical interventions are urgently needed.

Unprotected anal intercourse, risk reduction behaviours, and subsequent HIV infection in a cohort of homosexual men

Objective:A range of risk reduction behaviours in which homosexual men practise unprotected anal intercourse (UAI) has been described. We aimed to assess the extent of any reduction in HIV risk associated with these behaviours. Design:A prospective cohort study of HIV-negative homosexual men in Sydney, Australia. Methods:Men were followed up with 6-monthly detailed behavioural interviews and annual testing for HIV. The four risk reduction behaviours (behaviourally defined) examined were serosorting, negotiated safety, strategic positioning, and withdrawal during receptive UAI (UAI-R). Results:In 88% of follow-up periods in which UAI was reported, it occurred in the context of consistent risk reduction behaviours. Compared with those who reported no UAI, the risk of HIV infection was not raised in negotiated safety [hazard ratio = 1.67, 95% confidence interval (CI) 0.59–4.76] and strategic positioning (hazard ratio = 1.54, 95% CI 0.45–5.26). Serosorting outside negotiated safety was associated with an intermediate rate of HIV infection (hazard ratio = 3.11, 95% CI 1.09–8.88). Withdrawal was associated with a higher risk than no UAI (hazard ratio = 5.00, 95% CI 1.94–12.92). Patterns of UAI differed greatly according to partners serostatus. Men who reported serosorting were less likely to report either strategic positioning or withdrawal. Conclusion:Each behaviour examined was associated with an intermediate HIV incidence between the lowest and highest risk sexual behaviours. The inverse association between individual behaviours suggests that men who practise serosorting rely on this protection. The high prevalence of these behaviours demands that researchers address the contexts and risks associated with specific types of UAI.

Hepatitis C and Non-Hodgkin Lymphoma Among 4784 Cases and 6269 Controls From the International Lymphoma Epidemiology Consortium

BACKGROUND & AIMS Increasing evidence points towards a role of hepatitis C virus (HCV) infection in causing malignant lymphomas. We pooled case-control study data to provide robust estimates of the risk of non-Hodgkins lymphoma (NHL) subtypes after HCV infection. METHODS The analysis included 7 member studies from the International Lymphoma Epidemiology Consortium (InterLymph) based in Europe, North America, and Australia. Adult cases of NHL (n = 4784) were diagnosed between 1988 and 2004 and controls (n = 6269) were matched by age, sex, and study center. All studies used third-generation enzyme-linked immunosorbent assays to test for antibodies against HCV in serum samples. Participants who were human immunodeficiency virus positive or were organ-transplant recipients were excluded. RESULTS HCV infection was detected in 172 NHL cases (3.60%) and in 169 (2.70%) controls (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.40-2.25). In subtype-specific analyses, HCV prevalence was associated with marginal zone lymphoma (OR, 2.47; 95% CI, 1.44-4.23), diffuse large B-cell lymphoma (OR, 2.24; 95% CI, 1.68-2.99), and lymphoplasmacytic lymphoma (OR, 2.57; 95% CI, 1.14-5.79). Notably, risk estimates were not increased for follicular lymphoma (OR, 1.02; 95% CI, 0.65-1.60). CONCLUSIONS These results confirm the association between HCV infection and NHL and specific B-NHL subtypes (diffuse large B-cell lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma).

Rates of non-AIDS-defining cancers in people with HIV infection before and after AIDS diagnosis.

Objective To describe the incidence of non-AIDS-defining cancers in people with HIV infection before and after the occurrence of AIDS, and to examine the association of cancer risk with immune deficiency. Design Cohort study involving nation-wide linkage of HIV, AIDS and cancer registry data. Methods Association of cancer risk with immune deficiency was examined by analysing cancer risks in four periods between HIV diagnosis, AIDS and death. Results Linkage identified 196 cases of non-AIDS-defining cancer in 8351 people notified with HIV infection and 8118 registered with AIDS (total of 13 067 individuals). Overall, we found significantly increased rates of cancer of the lip, anus, Hodgkins disease, myeloma and leukaemia. Of these cancers, in people with HIV infection who did not develop AIDS, or were more than 5 years prior to development of AIDS, only cancer of the anus occurred at increased rates. A significant trend of increasing relative risk of cancer with increasing time since HIV diagnosis was found for Hodgkins disease and multiple myeloma. Conclusions People with HIV with mild immune deficiency prior to AIDS were at increased risk of anal cancer, but this may reflect other risk factors. Other cancers occurred only later in the course of HIV infection. This is reassuring evidence that people with HIV who are only mildly immune deficient may not be at increased risk of non-AIDS-defining cancers, but larger studies with longer periods of follow-up are needed to confirm this.