Incidence of Kaposi's sarcoma and HHV-8 seroprevalence among homosexual men with known dates of HIV seroconversion. Italian Seroconversion Study

OBJECTIVES: To evaluate temporal trends of Kaposi's sarcoma (KS) and of the KS-related human herpesvirus (HHV-8) among homosexual men who seroconverted for HIV between 1984 and 1997. METHODS: The study participants were 387 homosexual men. Changes over a period of time were assessed by estimating KS incidence rates per 1000 person-years for the periods 1984-1989, 1990-1992, 1993-1995, and 1996-1997. The proportional incidence of KS as the AIDS-defining disease for the same periods was also calculated. To evaluate a cohort effect of calendar period, Kaplan-Meier curves were used to estimate the risk of KS by period of HIV seroconversion [i.e. before 1990 (median year of seroconversion) versus later]. Relative hazards for the four periods were estimated using competitive-risks models. We also estimated HHV-8 seroprevalence over the study period. RESULTS: Forty-eight participants developed KS. Between 1984 and 1995, the incidence rate of KS per 1000 person-years increased from 3.9 to 32.8, whereas the proportional incidence decreased from 33.3 to 24.3%. The risk of developing KS after HIV seroconversion did not change when comparing the seroconversion periods (i.e. before 1990 versus later). HHV-8 seroprevalence also remained stable. The rates of KS and the relative hazards dramatically decreased after 1995. CONCLUSIONS: Although KS incidence rates increased up to 1995, the proportional incidence decreased, due to the higher increase in rates of other AIDS-defining diseases. The finding that the risk of developing KS after HIV seroconversion remained stable over time is consistent with the stable trend of HHV-8 seroprevalence. The dramatic decrease in KS incidence rates after 1995 coincides with combined antiretroviral therapy.     

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, Hodgkin's 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 Hodgkin's 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.     

The impact of highly active antiretroviral therapy on the incidence and outcomes of AIDS-defining cancers in Southern Alberta

OBJECTIVES: To determine the impact of highly active antiretroviral therapy (HAART) on the incidence and outcomes of Kaposi's sarcoma (KS), non-Hodgkin's lymphoma (NHL) and invasive cervical cancer/dysplasia in a well-defined geographical HIV-infected population between 1984 and 2005. METHODS: A clinic database search, chart review and verification with public health records were undertaken for all AIDS-defining cancers diagnosed in Southern Alberta before and after the introduction of HAART. RESULTS: A total of 2,137 patients with 9,265 person-years of HIV follow-up care were reviewed. One hundred and forty-three cases of KS, 64 cases of NHL and 11 cases of invasive cervical cancer/dysplasia were identified. KS and NHL together accounted for 15% of clinical presentations with an AIDS-defining illness that led to the HIV diagnosis. Following the introduction of HAART, the reduced number of severely immunocompromised patients was associated with 92 and 84% reductions in new diagnoses of KS and NHL, respectively, which were seen mainly in clinic patients declining or failing HAART. Crude reductions of 94 and 65% in mortality from KS and NHL, respectively, were also seen. The prevalences of KS, NHL and invasive cervical cancer/dysplasia have recently stabilized at 3, 1 and 5% of the population, respectively. CONCLUSIONS: The introduction of HAART has dramatically reduced the incidence of KS and NHL and improved survival from these cancers for most patients in HIV care. However, patients still present with KS and NHL leading to their HIV diagnosis.     

B-cell stimulation and prolonged immune deficiency are risk factors for non-Hodgkin's lymphoma in people with AIDS

OBJECTIVES: To identify risk factors for non-Hodgkin's lymphoma (NHL) in people with HIV infection. DESIGN AND SETTING: Case-control study in Sydney, Australia. PARTICIPANTS AND METHODS: Two hundred and nineteen patients with AIDS-related NHL were compared with 219 HIV-infected controls without NHL, matched for CD4 positive cell count and date of specimen collection. Data on demographic, infectious, treatment-related and immunological factors were abstracted by medical record review. The association between demographic factors, sexually transmissible diseases, HIV-related opportunistic infections, anti-viral therapy, duration of immune deficiency and indices of immune stimulation and risk of NHL were derived for these groups. RESULTS: In a multivariate model, there were two independent groups of predictors of NHL risk. The first was duration of immunodeficiency, as measured by longer time since seroconversion (P for trend 0.008), and lower CD4 positive cell count 1 year prior to the time of NHL diagnosis (P for trend 0.009). The second predictor was B-cell stimulation, as indicated by higher serum globulin (a surrogate marker for serum immunoglobulin, P for trend 0.044) and HIV p24 antigenaemia [odds ratio (OR) for p24 positivity, 1.82; 95% confidence interval (CI), 1.15-2.88]. Indices of B-cell stimulation preceded the diagnosis of NHL by several years. Factors not related to NHL risk included clinical indices of Epstein-Barr virus infection and receipt of individual nucleoside analogue antiretroviral agents. Combination therapy with these agents was associated with a non-significant reduction in NHL risk (OR, 0.68; 95% CI, 0.39-1.18). CONCLUSIONS: Markers of long-standing immune deficiency and B-cell stimulation were associated with an increased risk of developing NHL. Unless the strongest risk factor for NHL, immune deficiency, can be reversed, NHL is likely to become proportionately more important as a cause of morbidity and mortality in people with HIV infection.     

Trends in cancer risk among people with AIDS in the United States 1980-2002

BACKGROUND: People with AIDS have heightened cancer risk from immunosuppression. HAART has been available since 1996 and has reduced AIDS-related mortality, but there are few large-scale studies on cancer trends. METHODS: AIDS and cancer registries in 11 US regions (1980-2002) were used to identify cancers in 375 933 people with AIDS. Cancer risk relative to the general population was measured using the standardized incidence ratio (SIR), focusing on the 2 years after AIDS onset for those with AIDS in 1990-1995 and 1996-2002 (HAART era). Time trends were assessed with Poisson regression. RESULTS: Between 1990-1995 and 1996-2002, risk declined for the two major AIDS-defining cancers: Kaposi sarcoma [(KS) n = 5131; SIR, 22 100 and 3640, respectively; P < 0.0001] and non-Hodgkin lymphoma [(NHL) n = 3412; SIR, 53.2 and 22.6, respectively; P < 0.0001]. Declines began in the 1980s, but risk fell sharply in 1996 and was stable thereafter. Risk of cervical cancer did not change (n = 64; SIR, 4.2 and 5.3, respectively; P = 0.33). Among non-AIDS malignancies, lung cancer was most common, but risk declined between 1990-1995 and 1996-2002 (n = 344; SIR, 3.3 and 2.6, respectively; P = 0.02). Risk of Hodgkin lymphoma increased substantially over the 1990-2002 period (n = 149; SIR, 8.1 and 13.6, respectively; P = 0.003). CONCLUSIONS: Dramatic declines in KS and NHL were temporally related to improving therapies, especially introduction of HAART, but those with AIDS remain at marked risk. Among non-AIDS-related cancers, a recent increase in Hodgkin lymphoma was observed.     

AIDS and non-AIDS-related malignancies: a new vexing challenge in HIV-positive patients. Part I: Kaposi's sarcoma,non-Hodgkin's lymphoma,and Hodgkin's lymphoma

HIV-infected patients are at an increased risk for developing cancers. Three, in particular, are considered to be AIDS-defining malignancies: Kaposi's sarcoma (KS), non-Hodgkin's lymphoma (NHL), and cervical cancer. Other non-AIDS-defining malignancies have been reported in the setting of HIV infection as having an increased frequency compared with their incidence in the general population. One of those most frequently reported is Hodgkin's disease. As with KS and NHL, the problem of diagnosing and treating immunocompromised patients with cancer represents a formidable challenge. Moreover, a newly discovered human gamma-herpes virus, human herpes virus-8 (HHV-8), has been identified in over 90% of KS lesions from patients with and without AIDS, suggesting its etiological importance in the development of KS and new therapeutic approaches.     

Changing epidemiology and risk factors for gastrointestinal non-Hodgkin's lymphoma in a North American population: population-based study

OBJECTIVES: To assess the incidence, risk factors, and endoscopic presentation of gastrointestinal non-Hodgkin's lymphoma (GI NHL) in a large predominantly urban adult population sample.
METHODS: A comprehensive database review of all diagnoses of GI NHL in the Calgary Health Region over a 5-yr period (1999–2003) was undertaken. Longer-term data from a population-based HIV database (1985–2004) were also reviewed. A regional pathology database was used to corroborate case identification. All patients 18 yr of age or older were included. Age- and gender-adjusted incidence rates were calculated. Within the HIV-positive population, incidence rates were compared over time. Endoscopic appearances were assessed and compared.
RESULTS: Fifty-six GI NHL cases occurred during the study period. The age- and gender-adjusted annual incidence of GI NHL was 1.73 per 100,000 in the study population. The majority were diffuse large B-cell histology (54%), followed by lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) (29%). Increasing age, history of kidney transplant, and H. pylori positivity in MALT lymphoma were identified as risk factors. Within the HIV-positive population, a highly significant drop in GI NHL was seen over time, with an incidence of 3.86 per 1,000 patient-years in 1985–1989 compared to zero cases in 2000–2004, despite a greater prevalence of HIV disease ( P < 0.0001 for trend). MALT lymphoma was less likely to manifest as a mass on endoscopy versus other presentations ( P < 0.05).
CONCLUSIONS: Population-based GI NHL incidence rates in Calgary are higher than those described elsewhere in North America or in Britain. The incidence of GI NHL within the HIV population has virtually disappeared, presumably due to the advent of highly active retroviral therapy.     

The association of neoplasms and HIV infection in the correctional setting

HIV-associated immunosuppression has been linked to an increased risk of a number of cancers, including Kaposi sarcoma (KS), non-Hodgkin's lymphoma (NHL), and invasive cervical cancer. Because prison inmates constitute one of the highest HIV/AIDS prevalent populations in the US, understanding the link between HIV infection and cancer in the correctional setting holds particular public health relevance. The study population consisted of 336,668 Texas Department of Criminal Justice inmates who were incarcerated, for any duration, between 1 January 1999 and 31 December 2001. Inmates diagnosed with HIV infection exhibited elevated rates of KS, NHL, anal cancer, and Hodgkin's disease, after adjusting for age and race. The elevated rates of cancer among HIV-infected individuals, particularly prison inmates, may be mediated, in part, by high-risk behaviours. HIV-associated risk behaviours, including unsafe sexual practices, injection drug use, and prostitution may be associated with cancer-related risk behaviours, such as smoking, excessive alcohol consumption, and poor diet. It will be important for future investigators to examine the association between HIV infection and cancer risk with sufficiently large study cohorts and appropriate longitudinal designs.     

Risk of cancer in people with AIDS.

OBJECTIVES: To determine whether the incidence of cancers other than the AIDS-defining cancers is increased in people with AIDS, and to determine if cancer incidence increases with time, a surrogate marker of declining immune function. DESIGN: Register-based retrospective cohort study in New South Wales, Australia. Age-, sex-, and period-adjusted standardized incidence ratios (SIR) were calculated for individual cancers occurring in 1980-1993 in people with AIDS registered before 1996. RESULTS: During the study period, 3616 people were registered with AIDS; 716 cases of AIDS-defining cancer and 62 cases of non-AIDS-defining cancer were identified. People with AIDS had a significantly increased incidence of Hodgkin's disease [SIR 18.3; 95% confidence interval (CI) 8.39-34.8], multiple myeloma (SIR 12.1; 95% CI 2.50-35.4), leukaemia (SIR 5.76; 95% CI 1.57-14.7), lip cancer (SIR 5.94; 95% CI 1.92-13.8) and lung cancer (SIR 3.80; 95% CI 1.39-8.29). The incidence of Hodgkin's disease increased significantly around the time of AIDS diagnosis (P = 0.008 for trend with time), suggesting an association with immunodeficiency. CONCLUSIONS: This study provides strong support for the hypothesis that Hodgkin's disease is an AIDS-associated condition. There was an increased incidence of several other forms of cancer, some of which are known to occur at increased rates in transplant recipients who have received immunosuppressive therapy. Improved survival in people with HIV infection may lead to increases in the number that develop these forms of cancer.     

New therapy explains the fall in AIDS incidence with a substantial rise in number of persons on treatment expected

BACKGROUND: A marked decline in the number of reported AIDS cases has been observed in the United Kingdom, as in many industrialized countries, in 1996 and 1997. In England and Wales, a large reduction in AIDS cases has been recorded among homosexual and bisexual men. OBJECTIVES: To investigate, using data from the homosexuals and bisexuals in England and Wales as an example, possible explanations for the above decline such as the effects of new anti-retroviral therapies, or a decrease in the incidence of HIV in recent years. METHODS: A multistage model of HIV infection, HIV diagnosis, treatment and of AIDS diagnosis has been used to represent the pattern of HIV and AIDS incidence in homosexual and bisexual men in England and Wales up to the end of 1995. Scenarios for the post-1995 period were examined under different assumptions about changes in HIV incidence in recent years and treatment uptake and efficacy. RESULTS: The fall in the incidence of AIDS is unlikely to be the result of a reduction in HIV transmission during the 1990s. The most plausible explanation for this fall is the effect of new, more effective, anti-retroviral therapies. As a consequence, the number of individuals on treatment is likely to increase by 50 to 100% compared with the pre-1996 levels by the year 2001. Also, if the effect of the new therapies has a limited duration, or the use of such therapies is not well tolerated, the incidence of AIDS will rise again in the near future. CONCLUSIONS: These findings indicate that a substantial workload increase is under way for the healthcare system, and reiterate the need for measures to reduce HIV transmission as a means of bringing about a sustainable change in the incidence of AIDS.     

The world‐wide incidence of Kaposi's sarcoma in the HIV/AIDS era

Objectives

Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of endothelial origin typically occurring in the context of immunosuppression or immunodeficiency. Consequently, KS is one of the most common cancers in HIV‐infected individuals and frequently occurs among transplant recipients. Nevertheless, its incidence in different populations is not well understood.

Methods

We searched online databases for publications on KS incidence. A random‐effect meta‐analysis was performed to combine the KS incidences and incidence rate ratios (IRRs) for associated risk factors.

Results

Seventy‐six eligible studies representing 71 time periods were included. For HIV‐infected people, the overall KS incidence was 481.54 per 100 000 person‐years with a 95% confidential interval (CI) of 342.36–677.32 per 100 000 person‐years. HIV‐infected men who have sex with men (MSM) had the highest incidence of KS (1397.11 per 100 000 person‐years; 95% CI 870.55–2242.18 per 100 000 person‐years). The incidence of KS was significantly lower in female than in male individuals (IRR 3.09; 95% CI 1.70–5.62). People receiving highly active antiretroviral therapy (HAART) had a lower incidence compared with people who had never received HAART (IRR 6.57; 95% CI 1.91–24.69). The incidence of KS was 68.59 (95% CI 31.39–149.86) per 100 000 person‐years in transplant recipients, 52.94 (95% CI 39.90–70.20) per 100 000 person‐years in children with HIV infection, and 1.53 (95% CI 0.33–7.08) per 100 000 person‐years in the general population.

Conclusions

Globally, a relatively high incidence of KS was found among HIV‐seropositive people and, in particular, in HIV‐infected MSM. The introduction of HAART has largely prevented the development of KS, but it has not entirely removed the challenge of KS. In Africa, in particular, KS imposes a very heavy disease burden, which can mainly be attributed to the high prevalence of KS‐associated herpesvirus and poor access to HAART.

     

AIDS-related tumors: integrating antiviral and anticancer therapy

The introduction of highly active antiretroviral therapy (HAART) has changed dramatically the landscape of HIV disease. Deaths from AIDS-related diseases have been reduced by 75% since protease inhibitor therapy and combination antiretroviral therapy came into use in late 1995. While KS is declining, the situation for non-Hodgkin's lymphoma is more complex with a reduced incidence of primary central nervous system lymphoma, but a relative stability in the number of patients developing systemic NHL. AIDS-related NHL appears not to be markedly decreased by the introduction of HAART and it is the greatest therapeutic challenge in the area of AIDS oncology. The emphasis has now shifted to cure while maintaining vigilance regarding the unique vulnerability of HIV-infected hosts. Furthermore, also for the prolongation of the survival expectancy of these patients, other non-AIDS-defining tumors, such as Hodgkin's disease, anal, head and neck, lung and testicular cancer, and melanoma have been recently reported with increased frequency in patients with HIV infection.     

Trends in non-Hodgkin lymphoma (NHL) and HIV-associated NHL deaths in the United States

Since a significant number of lymphomas have been associated with the human immunodeficiency virus (HIV), the purpose of this study was to describe the impact of HIV infection on non-Hodgkin's lymphoma (NHL) mortality trends and demographics. Multiple-cause-of-death data for the United States from 1979 through 1996 were obtained from the National Center for Health Statistics, Centers for Disease Control and Prevention. Annual NHL deaths rates for the United States were calculated as the number of NHL deaths per 100,000 persons, based on estimates of the U.S. resident population. The time periods 1979-1982, 1986-1989, and 1993-1996 were examined for changes over time. To describe NHL and HIV infection mortality, the characteristics of NHL deaths with HIV infection listed anywhere on the death records were examined beginning in 1987. This study found that despite reports of a lower incidence rate of NHL among blacks with HIV/AIDS, death rates from lymphomas associated with HIV/AIDS have markedly increased in black males and females over time. It was also noted that in agreement with other studies, this study documented a decrease in NHL/HIV mortality in 1996.     

AIDS diagnoses at higher CD4 counts in Australia following the introduction of highly active antiretroviral treatment

OBJECTIVES: To assess whether AIDS cases in Australia have been diagnosed at higher CD4 counts since the widespread availability of highly active antiretroviral treatment (HAART) in mid-1996. METHODS: Data on the CD4 count at AIDS diagnosis for AIDS cases diagnosed between 1 January 1992 and 31 December 1997, and reported to the National AIDS Registry in Australia by 31 March 1998, were analysed. The median CD4 count at AIDS diagnosis, and the proportions of AIDS diagnoses with a CD4 count above 100 cells/microl, and above 200 cells/microl, were calculated by the year of diagnosis, both for all AIDS-defining illnesses, and for each illness separately. Analyses were also stratified by the time interval between HIV and AIDS diagnoses (less than or equal to, or more than, 3 months) because people diagnosed with HIV close to the diagnosis of AIDS would generally not have received any antiretroviral treatment before the diagnosis of AIDS, and so no trends in CD4 counts at the diagnosis of AIDS would be expected in this group. RESULTS: There was an increase in CD4 count at AIDS diagnosis in 1996 and 1997, although this increase was only apparent for AIDS-defining illnesses other than Pneumocystis carinii pneumonia (PCP), and was limited to AIDS cases diagnosed with HIV more than 3 months before AIDS. In cases of AIDS other than PCP, and diagnosed with HIV more than 3 months before AIDS, the median CD4 count increased from 50 cells/microl in 1995 to 80 cells/microl in 1996 and 134 cells/microl in 1997. CONCLUSIONS: There has been an increase in the CD4 count at AIDS diagnosis for most AIDS-defining illnesses in Australia coincident with the widespread availability of HAART.     

Risk of cancer in patients with HIV disease. London African HIV/AIDS Study Group

The aim of this study was to compare cancer incidence in a cohort of HIV-infected patients with the incidence rates in the population of South East England. Data collected for a retrospective cohort study of 2048 HIV-infected patients were analysed to examine the incidence of cancer. Cases of cancer occurring in South East England from 1985-1995 were obtained from the Thames Cancer Registry. Standardized incidence ratios were calculated by comparison of the observed number of cases for each cancer type in HIV-infected non-Africans with the numbers expected, calculated from the age and sex specific registration rates for the South East England population using person-years of observation. The crude incidence rates of cancer were calculated for HIV-infected Africans. The incidence of non-AIDS defining cancers such as Hodgkin's disease (standardized incidence ratio 22; 95% CI: 3-80) and anal cancer (standardized incidence ratio 125; 95% CI: 3-697) were significantly increased for non-African males with HIV disease. Anal cancer was also significantly increased for non-African females (standardized incidence ratio 1667; 95% CI: 43-9287). Kaposi's sarcoma (KS) was the commonest cancer among HIV-infected Africans and males had an incidence which was nearly 3 times that of females. There is evidence to suggest that the risks for other non-AIDS defining cancers were significantly increased in persons with HIV disease which may have implications for HIV/AIDS surveillance.     

HIV-related non-Hodgkin's lymphoma among European AIDS patients

Abstract: The epidemiology of HIV associated non-Hodgkin's lymphoma (NHL) was investigated in 6550 European patients with AIDS. NHL was diagnosed in 3.5% of all patients at the time of the AIDS diagnosis. Although the probability of being diagnosed with NHL at AIDS diagnosis was significantly higher among intravenous drug users than among homosexual men, and was associated with increasing age, the observed incidences of NHL were more strikingly similar than any differences. The rate of developing NHL after a previous AIDS diagnosis was 2.4 per 100 patient years of follow-up, and remained constant during a 5-year follow-up period. While primary brain lymphomas comprised only 9% of NHL diagnosed at the time of AIDS, they comprised 38% of NHL diagnosed after AIDS (p<0.001). The prognosis for patients with NHL at AIDS diagnosis was poor with a median survival of 5 months. A diagnosis of primary brain lymphoma was uniformly associated with a poor outcome. It is concluded that the probability of developing NHL in late stage HIV infection is lower than previously anticipated from the results of small studies on patients receiving long-term anti-retroviral therapy.     

Estimating the population impact in Australia of improved antiretroviral treatment for HIV infection

OBJECTIVE: To estimate the reduction in AIDS incidence, if any, which has occurred in Australia following the availability of new combination antiretroviral treatments from 1995. DESIGN: Analyses were based on national surveillance data. METHODS: Back-projection analyses based on quarterly AIDS counts to the end of 1994 were used to estimate the numbers of AIDS diagnoses which would have occurred if new treatments had not reduced the rate of progression to AIDS. Estimates of the reduction in AIDS diagnoses between 1995 and 1998 were made by subtracting the observed delay-adjusted AIDS counts from the predicted AIDS incidence. RESULTS: AIDS incidence between 1995 and 1998 was estimated to have been reduced by 1093 cases (33%) following the availability of new antiretroviral treatments (95% confidence interval 831 (25%) to 1425 (43%) cases). The majority of this reduction in AIDS incidence was estimated to have occurred during 1997 (434 cases) and 1998 (427 cases). CONCLUSIONS: AIDS incidence in Australia has declined since 1995 coincidental with introduction of new antiretroviral treatments. In particular, the more rapid decline in AIDS incidence since mid-1996 coincided with the availability and widespread uptake of combinations including protease inhibitors.     

Decreasing trends of bacteraemia among HIV-infected Ugandan adults: incidence, aetiology, clinical outcomes and effect of antiretroviral therapy in a semi-urban setting (2000-2008)

Objective To investigate the effect of antiretroviral therapy on trends of incidence, aetiology and clinical outcomes of bacteraemia among HIV‐infected Ugandans in a semi‐urban setting. Methods A cohort of HIV‐1‐infected Ugandans aged 15 or older was followed from 2000 to 2008. Clinical, haematological and immunological measurements were taken at 6‐monthly visits. Additionally, patients reported to outpatient clinics whenever they were ill. Patients with elevated axillary temperature above 37.4 °C consistently triggered clinical assessment (with mandatory blood cultures) and empirical management protocol. Daily cotrimoxazole prophylaxis and highly active antiretroviral therapy (HAART) were introduced stepwise to eligible patients in August 2000 and February 2003, respectively. We compared the rates of bacteraemia across five calendar periods using random‐effects Poisson regression for the effect of HAART at the population level. Results A total of 246 bacteraemia episodes (including multiple episodes) were documented among 188 individuals (crude incidence: 42.4 events per 1000 person‐years; 95% CI: 35.0, 51.4). The most common species isolated was Streptococcus pneumoniae. After adjustment for current age, clinical characteristics at enrolment (CD4+ T‐cell counts and WHO stage) and time since enrolment, the incidence of bacteraemia dropped significantly when HAART was widely available compared with the period when treatment was not available (adjusted hazard ratio: 0.17; 95% CI: 0.09, 0.35). No poor health outcomes (death or lack of clinical response to antibiotics) after bacteraemia occurred after complete access to HAART. Conclusions HAART availability in a resource‐poor setting substantially reduced the trends of bacteraemia among HIV‐infected adults. This may further impact on future morbidity and healthcare costs of HIV‐infected people.     

Castleman's disease and HIV infection in Australia

OBJECTIVES: To describe, retrospectively, the Australian experience of multi-centric Castleman's disease (MCD) in the setting of HIV infection, specifically with the advent of HAART, and newer chemotherapeutic agents. PATIENTS AND METHODS: HIV-infected patients diagnosed with MCD since 1994, were identified from three major HIV treatment centres in Australia. Demographic and disease characteristic variables were collated by the National Centre in HIV Epidemiology and Clinical Research. RESULTS: Eleven patients were identified with MCD. Medial follow up was 46 (18-57) months. All had CD4 cell counts less than 500 cells/microL. All but one patient was receiving HAART at the time of diagnosis. Nine of the 11 patients had Kaposi's sarcoma (KS) and two patients also developed non-Hodgkin's Lymphoma (NHL). All patients received chemotherapy for MCD. The response rate from Chemotherapy was 64%. Only two patients achieved sustained remissions. The median survival was 21.9 (1-52) months. The mortality was 45% from MCD and its related complications. CONCLUSION: MCD in HIV infected patients is a rare and life-threatening disorder. There is limited recent information on optimal treatment for MCD. MCD in our series appeared to be a chemo-responsive disease. In our experience, treatment with liposomal anthracycline was associated with good response rates and acceptable toxicity in several patients, and therefore merits further exploration to establish its role. Treatment in the future may concentrate on novel agents such as anti-interleukin 6, anti-CD20 antibodies, thalidomide and viral ablation.     

Pneumococcal pneumonia in HIV-infected patients by antiretroviral therapy periods

OBJECTIVE: To ascertain the relationship between periods of various antiretroviral therapies and the incidence of first community-acquired pneumococcal pneumonia (CAPP) among HIV-1 infected patients. METHODS: We analysed 4075 patients enrolled prospectively in the Lyon section of the French Hospital Database on HIV between 1993 and 2004, stratified into three groups. The first group (G1) included patients for whom enrolment and last follow-up were before the highly active antiretroviral therapy (HAART) period (beginning 1 July 1996); the second group (G2) comprised patients who were enrolled before HAART but had last follow-up in the HAART period; the third group (G3) included patients for whom both enrolment and last follow-up took place in the HAART period. RESULTS: Fifty-five CAPP episodes were identified. The incidence of CAPP per 1000 patient-years declined over time, from 10.6 to 1.5 and 2.5 in calendar periods G1, G2 and G3, respectively (P=0.004 for linear trend). Factors associated with a decreased risk of CAPP were lower age, baseline CD4 count >or=200 cells/microL and more recent years of enrolment, when HAART use became extensive (P<0.001). The use of intravenous drugs increased the risk of CAPP (P<0.001). CONCLUSIONS: There has been a significant reduction in the incidence of CAPP in HIV-1 infected patients since the advent of HAART.