ABSTRACT
BACKGROUND: Women with HIV are globally underrepresented in clinical research. Existing studies often focus on reproductive outcomes, seldom focus on older women, and are often underpowered to assess sex/gender differences. We describe CD4, HIV viral load (VL), clinical characteristics, comorbidity burden, and use of antiretroviral therapy (ART) among women with HIV in the RESPOND study and compare them with those of the men in RESPOND. METHODS: RESPOND is a prospective, multi-cohort collaboration including over 34 000 people with HIV from across Europe and Australia. Demographic and clinical characteristics, including CD4/VL, comorbidity burden, and ART are presented at baseline, defined as the latter of 1 January 2012 or enrolment into the local cohort, stratified by age and sex/gender. We further stratify men by reported mode of HIV acquisition, men who have sex with men (MSM) and non-MSM. RESULTS: Women account for 26.0% (n = 9019) of the cohort, with a median age of 42.2 years (interquartile range [IQR] 34.7-49.1). The majority (59.3%) of women were white, followed by 30.3% Black. Most women (75.8%) had acquired HIV heterosexually and 15.9% via injecting drug use. Nearly half (44.8%) were receiving a boosted protease inhibitor, 31.4% a non-nucleoside reverse transcriptase inhibitor, and 7.8% an integrase strand transfer inhibitor. The baseline year was 2012 for 73.2% of women and >2019 for 4.2%. Median CD4 was 523 (IQR 350-722) cells/µl, and 73.6% of women had a VL <200 copies/mL. Among the ART-naïve population, women were more likely than MSM but less likely than non-MSM (p < 0.001) to have CD4 <200 cells/µL and less likely than both MSM and non-MSM (p < 0.001) to have VL ≥100 000 copies/mL. Women were also more likely to be free of comorbidity than were both MSM and non-MSM (p < 0.0001). CONCLUSION: RESPOND women are diverse in age, ethnicity/race, CD4/VL, and comorbidity burden, with important differences relative to men. This work highlights the importance of stratification by sex/gender for future research that may help improve screening and management guidelines specifically for women with HIV.
ABSTRACT
Heterosexuals living with HIV report feeling additional HIV stigma compared to homosexual men, which may affect clinical outcomes. Yet, beyond routinely collected surveillance data, little is known about the characteristics of individuals who acquire HIV heterosexually and clinical outcomes by mode of sexual acquisition have not been directly compared. Using data from the Australian HIV Observational Database, we compared clinical characteristics of those with heterosexually-acquired (Het-HIV) to homosexually-acquired HIV (Hom-HIV) to investigate any differences and their implications for clinical management. 513 Het-HIV and 1467 Hom-HIV patients were included and contributed 3,127 and 9,457 person-years of follow-up, respectively. Compared with Hom-HIV, Het-HIV were more often born outside Australia (62.5% vs 39.9%, p<0.001), less likely to have Hepatitis C (4.8% vs 7.8%, p=0.029) and had lower median CD4 counts at diagnosis (292 vs 450 cells/µL, p<0.001) and cART initiation (270 vs 340 cells/µL, p<0.001). Despite these lower CD4 counts, there were no significant differences between groups for time to the major clinical endpoints of cART initiation, viral suppression, virological failure or all-cause mortality. Het-HIV had a lower risk of loss-to-follow-up than Hom-HIV (aHR 0.78; 95% CI 0.64-0.95). Further studies examining factors associated with, and interventions to inform retention in care are required.
Subject(s)
HIV Infections , Australia/epidemiology , CD4 Lymphocyte Count , HIV Infections/drug therapy , HIV Infections/epidemiology , Heterosexuality , Homosexuality , Humans , MaleABSTRACT
OBJECTIVES: Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real-world settings are limited. METHODS: The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12 ± 3 months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL < 200 HIV-1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4 count > 750 cells/µL or a 33% increase where the baseline CD4 count was ≥ 500 cells/µL. Poisson regression compared clinical failures (AIDS/death ≥ 14 days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint. RESULTS: Of 5198 ART-naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs; 880 (17.4%) were aged > 50 years, 2539 (49.4%) had CD4 counts < 350 cells/µL and 1891 (36.8%) had VL > 100 000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40-50 and > 50 years), CD4 count categories (≤ 350 vs. > 350 cells/µL) and VL categories at ART initiation (≤ 100 000 vs. > 100 000 copies/mL), with all investigated interactions being nonsignificant (P > 0.05). CONCLUSIONS: Differences among ART classes in virological, immunological and clinical outcomes in ART-naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.
Subject(s)
HIV Infections/drug therapy , HIV Integrase Inhibitors/therapeutic use , HIV-1/genetics , Protease Inhibitors/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , Adult , CD4 Lymphocyte Count , Cohort Studies , Female , HIV Infections/immunology , HIV Infections/virology , HIV Integrase Inhibitors/pharmacology , HIV-1/drug effects , Humans , International Cooperation , Logistic Models , Male , Middle Aged , Protease Inhibitors/pharmacology , RNA, Viral/drug effects , Reverse Transcriptase Inhibitors/pharmacology , Treatment Outcome , Viral LoadABSTRACT
OBJECTIVES: As HIV-positive people age, diagnosis and management of comorbidities associated with ageing are of increasing concern. In this study, we aimed to compare the self-reported prevalences of heart disease, stroke, thrombosis and diabetes in older Australian HIV-positive and HIV-negative gay and bisexual men (GBM). METHODS: We analysed data from the Australian Positive & Peers Longevity Evaluation Study (APPLES), a study of a prospectively recruited cross-sectional sample of 228 (51.1%) HIV-positive and 218 (48.9%) HIV-negative GBM, aged ≥ 55 years. Regression methods were used to assess the association of HIV status with self-reported comorbidities. RESULTS: Of 446 patients, 389 [200 (51.4%) HIV-positive] reported their disease history. The reported prevalence of comorbidities was higher in the HIV-positive group than in the HIV-negative group: heart disease, 19.5 versus 12.2%; stroke, 7.5 versus 4.2%; thrombosis, 10.5 versus 4.2%; and diabetes, 15.0 versus 9.0%, respectively. In adjusted analyses, HIV-positive GBM had significantly increased odds of reporting heart disease [adjusted odds ratio (aOR) 1.99; P = 0.03] and thrombosis (aOR 2.87; P = 0.01). In our analysis, HIV status was not significantly associated with either age at diagnosis of heart disease (median 53 years for HIV-positive GBM versus 55 years for HIV-negative GBM; P = 0.64) or 5-year cardiovascular disease (CVD) risk estimated using the Framingham risk score. CONCLUSIONS: HIV-positive GBM more commonly reported heart disease and thrombosis compared with their HIV-negative peers. These results further highlight the need to understand the impact of HIV on age-related comorbidities in GBM, to guide optimal screening and treatment strategies to reduce the risk of these comorbidities among the HIV-positive population.
Subject(s)
Cardiovascular Diseases/epidemiology , Diabetes Mellitus/epidemiology , HIV Infections/epidemiology , Homosexuality, Male/statistics & numerical data , Sexual and Gender Minorities/statistics & numerical data , Aged , Australia/epidemiology , Comorbidity , Cross-Sectional Studies , Humans , Male , Middle Aged , Prevalence , Prospective StudiesABSTRACT
Paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 12 weeks are approved for treatment of chronic HCV genotype 1 infection. This study assessed the efficacy of shortened duration paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 8 weeks among people with recent HCV infection. In this open-label single-arm trial conducted in Australia, England and New Zealand, adults with recent HCV (duration of infection <12 months) received paritaprevir/ritonavir/ombitasvir and dasabuvir (with weight-based ribavirin for genotypes 1a and 1, no subtype) for 8 weeks. The primary endpoint was sustained virological response at 12 weeks post-treatment (SVR12) in the intention-to-treat (ITT) population. Thirty people (median age 38 years, male 93%) commenced treatment (with ribavirin, 97%), of whom 77% (n = 23) were HIV-positive, 93% (n = 28) had genotype 1a infection and 53% (n = 16) had ever injected drugs. Median maximum ALT in the preceding 12 months was 433 IU/L (IQR 321, 1012). Acute clinical hepatitis with ALT > 10 x ULN was documented in 83% (n = 25); one participant (3%) had jaundice. At baseline, median estimated duration of infection was 30 weeks (range 11, 51), and median HCV RNA was 5.7 log10 IU/mL (range 2.7, 7.3). SVR12 was achieved in 97% (29/30; early discontinuation at week 2, n = 1; per protocol 100%, 29/29). No relapse or reinfection was observed. In conclusion, paritaprevir/ritonavir/ombitasvir and dasabuvir (with ribavirin) for eight weeks were highly effective among HIV-positive and HIV-negative individuals with recent HCV infection. These data support the use of this shortened duration direct-acting antiviral regimen in this population.
Subject(s)
Antiviral Agents/administration & dosage , Hepacivirus/genetics , Hepatitis C/drug therapy , 2-Naphthylamine , Adult , Anilides/administration & dosage , Anilides/adverse effects , Anilides/pharmacology , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , Australia/epidemiology , Carbamates/administration & dosage , Carbamates/adverse effects , Carbamates/pharmacology , Cyclopropanes , Drug Administration Schedule , Drug Therapy, Combination , England/epidemiology , Female , Genotype , Hepacivirus/drug effects , Hepatitis C/epidemiology , Hepatitis C/virology , Humans , Intention to Treat Analysis , Lactams, Macrocyclic , Macrocyclic Compounds/administration & dosage , Macrocyclic Compounds/adverse effects , Macrocyclic Compounds/pharmacology , Male , Middle Aged , New Zealand/epidemiology , Proline/analogs & derivatives , Prospective Studies , RNA, Viral/blood , Ribavirin/administration & dosage , Ribavirin/adverse effects , Ribavirin/pharmacology , Ritonavir/administration & dosage , Ritonavir/adverse effects , Ritonavir/pharmacology , Safety , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Sulfonamides/pharmacology , Treatment Outcome , Uracil/administration & dosage , Uracil/adverse effects , Uracil/analogs & derivatives , Uracil/pharmacology , ValineABSTRACT
One challenge to HCV elimination through therapeutic intervention is reinfection. The aim of this analysis was to calculate the incidence of HCV reinfection among both HIV-positive and HIV-negative individuals treated for recent HCV infection (estimated infection duration <18 months). Individuals with recent HCV infection who achieved an end-of-treatment response in four open-label studies between 2004 and 2015 in Australia and New Zealand were assessed for HCV reinfection, confirmed by sequencing of the Core-E2 and/or NS5B regions. Reinfection incidence was calculated using person-time of observation. Exact Poisson regression analysis was used to assess factors associated with HCV reinfection. The cohort at risk for reinfection (n=120; 83% male; median age 36 years) was composed of HIV-positive men-who-have-sex-with-men (53%) and people who inject drugs (current 49%, ever 69%). Total follow-up time at risk was 135 person-years (median 1.08 years, range 0.17, 2.53). Ten cases of HCV reinfection were identified, for an incidence of 7.4 per 100 py (95% CI 4.0, 13.8). Reinfection incidence was significantly higher among participants who reported injection drug use at end of or post-treatment, irrespective of HIV status (15.5 per 100 py, 95% CI 7.8, 31.1). In adjusted analysis, factors associated with reinfection were older age (aIRR 5.3, 95% CI 1.15, 51.5, P=.042) and injection drug use at end of or post-treatment (aIRR 7.9, 95% CI 1.6, 77.2, P=.008). High reinfection incidence following treatment for recent HCV infection in individuals with ongoing risk behaviour emphasizes the need for post-treatment surveillance, harm reduction strategies and education in at-risk populations.
Subject(s)
Anti-Retroviral Agents/therapeutic use , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Adult , Australia/epidemiology , Female , Follow-Up Studies , Genotype , Genotyping Techniques , Hepacivirus/classification , Hepacivirus/genetics , Hepacivirus/isolation & purification , Humans , Incidence , Male , Middle Aged , New Zealand/epidemiology , Phylogeny , Recurrence , Risk Factors , Risk-Taking , Sequence Analysis, DNA , Viral Proteins/geneticsABSTRACT
OBJECTIVES: There is evidence that HIV-positive patients are suffering from a greater burden of morbidity as they age due to nonAIDS-related complications. To date it has been difficult to determine what part of this excess risk is due to the health effects of HIV, its treatment or to lifestyle factors common to gay and bisexual men (GBM). We calculated overall and cause-specific hospitalisation rates and risk factors for hospitalisations in HIV-negative and HIV-positive cohorts of GBM and compare these with rates in the general male population. METHODS: We conducted a record linkage study, linking two cohorts of HIV-negative (n = 1325) and HIV-positive (n = 557) GBM recruited in Sydney, New South Wales (NSW), Australia with the NSW hospital discharge data register. We compared rates of hospitalisation in the two cohorts and risk factors for hospitalisation using random-effects Poisson regression methods. Hospitalisation rates for each cohort were further compared with those in the general male population using indirect standardisation. RESULTS: We observed 2032 hospitalisations in the HIV-negative cohort during 13,016 person-years (PYs) [crude rate: 15.6/100 PYs (95% CI: 14.9-16.3)] and 2130 hospitalisations in the HIV-positive cohort during 5571 PYs [crude rate: 38.2/100 PYs (95% CI: 36.6-39.9)]. HIV-positive individuals had an increased risk of hospitalisation compared with the HIV-negative individuals [adjusted-IRR: 2.34 (95% CI: 1.91-2.86)] and the general population [SHR: 1.45 (95% CI: 1.33-1.59)]. Hospitalisation rates were lower in the HIV-negative cohort compared with the general population [SHR: 0.72 (95% CI: 0.67-0.78)]. The primary causes of hospitalisation differed between groups. CONCLUSIONS: HIV-positive GBM continue to experience excess morbidity compared with HIV-negative GBM men and the general population. HIV-negative GBM had lower morbidity compared with the general male population suggesting that GBM identity does not confer excess risk.
Subject(s)
Bisexuality/statistics & numerical data , HIV Infections/epidemiology , Homosexuality, Male/statistics & numerical data , Hospitalization/statistics & numerical data , Adult , Australia/epidemiology , Cohort Studies , Comorbidity/trends , Humans , Male , Middle Aged , Regression Analysis , Risk FactorsABSTRACT
OBJECTIVES: We established a subcohort of HIV-positive individuals from 10 sexual health clinics within the Australian HIV Observational Database (AHOD). The aim of this study was to assess demographic and other factors that might be associated with an incident sexually transmitted infection (STI). METHODS: The cohort follow-up was from March 2010 to March 2013, and included patients screened at least once for an STI. We used survival methods to determine time to first new and confirmed incident STI infection (chlamydia, gonorrhoea, syphilis or genital warts). Factors evaluated included sex, age, mode of HIV exposure, year of AHOD enrolment, hepatitis B or C coinfection, time-updated CD4 cell count, time-updated HIV RNA viral load, and prior STI diagnosis. RESULTS: There were 110 first incident STI diagnoses observed over 1015 person-years of follow-up, a crude rate of 10.8 [95% confidence interval (CI) 9.0-13.0] per 100 person-years. Factors independently associated with increased risk of incident STI included younger age [≥ 50 vs. 30-39 years old, adjusted hazards ratio (aHR) 0.4; 95% CI 0.2-0.8; P < 0.0001]; prior STI infection (aHR 2.5; 95% CI 1.6-3.8; P < 0.001), and heterosexual vs. men who have sex with men (MSM) as the likely route of exposure (aHR 0.2; 95% CI 0.1-0.6; P < 0.001). CONCLUSIONS: In this cohort of individualsbeing treated with antiretroviral drugs, those who were MSM, who were 30-39 years old, and who had a prior history of STI, were at highest risk of a further STI diagnosis.
Subject(s)
Condylomata Acuminata/epidemiology , HIV Infections/complications , Sexually Transmitted Diseases, Bacterial/epidemiology , Adult , Anti-HIV Agents/therapeutic use , Follow-Up Studies , HIV Infections/drug therapy , Humans , Middle Aged , Prospective Studies , Risk FactorsABSTRACT
BACKGROUND: Australia has increased coverage of antiretroviral treatment (ART) over the past decade, reaching 73% uptake in 2014. While ART reduces AIDS-related deaths, accumulating evidence suggests that it could also bolster prevention efforts by reducing the risk of HIV transmission ('treatment as prevention'). While promising, evidence of community-level impact of treatment as prevention on reducing HIV incidence among gay and bisexual men is limited. We describe a study protocol that aims to determine if scale up of testing and treatment for HIV leads to a reduction in community viraemia and, in turn, if this reduction is temporally associated with a reduction in HIV incidence among gay and bisexual men in Australia's two most populous states. METHODS: Over the period 2009 to 2017, we will establish two cohorts making use of clinical and laboratory data electronically extracted retrospectively and prospectively from 73 health services and laboratories in the states of New South Wales and Victoria. The 'positive cohort' will consist of approximately 13,000 gay and bisexual men (>90% of all people living with HIV). The 'negative cohort' will consist of at least 40,000 HIV-negative gay and bisexual men (approximately half of the total population). Within the negative cohort we will use standard repeat-testing methods to calculate annual HIV incidence. Community prevalence of viraemia will be defined as the proportion of men with a viral load ≥200RNA copies/mm3, which will combine viral load data from the positive cohort and viraemia estimates among those with an undiagnosed HIV infection. Using regression analyses and adjusting for behavioural and demographic factors associated with infection, we will assess the temporal association between the community prevalence of viraemia and the incidence of HIV infection. Further analyses will make use of these cohorts to assess incidence and predictors of treatment initiation, repeat HIV testing, and viral suppression. DISCUSSION: This study will provide important information on whether 'treatment as prevention' is associated with a reduction in HIV incidence at a community level among gay and bisexual men.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Adult , Australia/epidemiology , Bisexuality , Cohort Studies , HIV/genetics , HIV/isolation & purification , HIV Infections/epidemiology , HIV Infections/virology , Homosexuality, Male , Humans , Longitudinal Studies , Male , Prevalence , RNA, Viral/blood , Retrospective Studies , Viral LoadABSTRACT
OBJECTIVES: The aim of the study was to statistically model the relative increased risk of cardiovascular disease (CVD) per year older in Data collection on Adverse events of anti-HIV Drugs (D:A:D) and to compare this with the relative increased risk of CVD per year older in general population risk equations. METHODS: We analysed three endpoints: myocardial infarction (MI), coronary heart disease (CHD: MI or invasive coronary procedure) and CVD (CHD or stroke). We fitted a number of parametric age effects, adjusting for known risk factors and antiretroviral therapy (ART) use. The best-fitting age effect was determined using the Akaike information criterion. We compared the ageing effect from D:A:D with that from the general population risk equations: the Framingham Heart Study, CUORE and ASSIGN risk scores. RESULTS: A total of 24 323 men were included in analyses. Crude MI, CHD and CVD event rates per 1000 person-years increased from 2.29, 3.11 and 3.65 in those aged 40-45 years to 6.53, 11.91 and 15.89 in those aged 60-65 years, respectively. The best-fitting models included inverse age for MI and age + age(2) for CHD and CVD. In D:A:D there was a slowly accelerating increased risk of CHD and CVD per year older, which appeared to be only modest yet was consistently raised compared with the risk in the general population. The relative risk of MI with age was not different between D:A:D and the general population. CONCLUSIONS: We found only limited evidence of accelerating increased risk of CVD with age in D:A:D compared with the general population. The absolute risk of CVD associated with HIV infection remains uncertain.
Subject(s)
Coronary Disease/etiology , HIV Infections/complications , Myocardial Infarction/etiology , Stroke/etiology , Adult , Age Factors , Aged , Anti-HIV Agents/adverse effects , HIV Infections/drug therapy , Humans , Male , Middle Aged , Prospective Studies , Regression Analysis , Risk FactorsABSTRACT
OBJECTIVES: The aim of this study was to describe the long-term changes in CD4 cell counts beyond 5 years of combination antiretroviral therapy (cART). If natural ageing leads to a long-term decline in the immune system via low-grade chronic immune activation/inflammation, then one might expect to see a greater or earlier decline in CD4 counts in older HIV-positive patients with increasing duration of cART. METHODS: Retrospective and prospective data were examined from long-term virologically stable HIV-positive adults from the Australian HIV Observational Database. We estimated mean CD4 cell count changes following the completion of 5 years of cART using linear mixed models. RESULTS: A total of 37 916 CD4 measurements were observed for 892 patients over a combined total of 9753 patient-years. Older patients (> 50 years old) at cART initiation had estimated mean (95% confidence interval) changes in CD4 counts by year-5 CD4 count strata (< 500, 500-750 and > 750 cells/µL) of 14 (7 to 21), 3 (-5 to 11) and -6 (-17 to 4) cells/µL/year. Of the CD4 cell count rates of change estimated, none were indicative of long-term declines in CD4 cell counts. CONCLUSIONS: Our results suggest that duration of cART and increasing age do not result in decreasing mean changes in CD4 cell counts for long-term virologically suppressed patients, indicating that the level of immune recovery achieved during the first 5 years of treatment is sustained through long-term cART.
Subject(s)
Aging/immunology , Antiretroviral Therapy, Highly Active , CD4-Positive T-Lymphocytes , HIV Infections/drug therapy , HIV Infections/immunology , Adult , CD4 Lymphocyte Count , Drug Therapy, Combination , Female , Humans , Linear Models , Male , Middle Aged , Prospective Studies , Retrospective StudiesABSTRACT
OBJECTIVES: 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). METHODS: 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. RESULTS: 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 < 100 cells/µL to 2.4/1000 PY (95% CI 1.62-3.39/1000 PY) for CD4 counts > 350 cells/µL. Lower CD4 cell count and prior AIDS diagnoses were significant predictors for both ADCs and NADCs. CONCLUSIONS: 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.
Subject(s)
Acquired Immunodeficiency Syndrome/epidemiology , Anti-HIV Agents/therapeutic use , Anus Neoplasms/epidemiology , Hodgkin Disease/epidemiology , Lung Neoplasms/epidemiology , Lymphoma, AIDS-Related/epidemiology , Melanoma/epidemiology , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/immunology , Adult , Aging , Antiretroviral Therapy, Highly Active , Anus Neoplasms/immunology , Australia/epidemiology , CD4 Lymphocyte Count , Databases, Factual , Female , Follow-Up Studies , Hodgkin Disease/immunology , Humans , Logistic Models , Lung Neoplasms/immunology , Lymphoma, AIDS-Related/drug therapy , Lymphoma, AIDS-Related/immunology , Male , Melanoma/immunology , Middle Aged , Prospective Studies , Risk FactorsSubject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Time-to-Treatment/trends , Adolescent , Adult , Aged , Aged, 80 and over , Antiretroviral Therapy, Highly Active , Australia/epidemiology , CD4 Lymphocyte Count , Female , HIV Infections/immunology , HIV Infections/mortality , Humans , Male , Middle Aged , Practice Guidelines as Topic , Young AdultABSTRACT
OBJECTIVES: The aim of the study was to estimate the rates of cardiovascular disease (CVD) events after stopping smoking in patients with HIV infection. METHODS: Patients who reported smoking status and no previous CVD prior to enrolment in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study were included in this study. Smoking status is collected at each visit as current smoker (yes/no) and ever smoker (yes/no). Time since stopping smoking was calculated for persons who had reported current smoking during follow-up and no current smoking subsequently. Endpoints were: myocardial infarction (MI); coronary heart disease (CHD: MI plus invasive coronary artery procedure or death from other CHD); CVD (CHD plus carotid artery endarterectomy or stroke); and all-cause mortality. Event rates were calculated for never, previous and current smokers, and smokers who stopped during follow-up. Incidence rate ratios (IRRs) were determined using Poisson regression adjusted for age, sex, cohort, calendar year, family history of CVD, diabetes, lipids, blood pressure and antiretroviral treatment. RESULTS: A total of 27 136 patients had smoking status reported, with totals of 432, 600, 746 and 1902 MI, CHD, CVD and mortality events, respectively. The adjusted IRR of CVD in patients who stopped smoking during follow-up decreased from 2.32 within the first year of stopping to 1.49 after >3 years compared with those who never smoked. Similar trends were observed for the MI and CHD endpoints. Reductions in risk were less pronounced for all-cause mortality. CONCLUSION: The risk of CVD events in HIV-positive patients decreased with increasing time since stopping smoking. Smoking cessation efforts should be a priority in the management of HIV-positive patients.
Subject(s)
Cardiovascular Diseases/epidemiology , HIV Infections/complications , Smoking Cessation/statistics & numerical data , Smoking/adverse effects , Adult , Argentina/epidemiology , CD4 Lymphocyte Count , Cardiovascular Diseases/etiology , Cardiovascular Diseases/psychology , Cohort Studies , Europe/epidemiology , Female , HIV Infections/epidemiology , HIV Infections/psychology , Humans , Incidence , Male , Middle Aged , Prospective Studies , Risk Factors , Smoking Cessation/psychology , United States/epidemiologyABSTRACT
OBJECTIVES: The aim of the study was to determine whether combination antiretroviral therapy (cART) with high central nervous system penetration-effectiveness (CPE) rank (neurocART) is associated with increased survival benefit compared with non-neurocART. METHODS: Prospective data were examined for HIV-positive patients in the Asia Pacific HIV Observational Database who had commenced cART. CPE rank was calculated using the 2010 rankings process. NeurocART status was assigned to regimens with a CPE rank of 8 or more. Survival was analysed using Cox proportional hazards models with covariates updated at changes in cART regimen and with deaths up to 90 days after regimen cessation attributed to that regimen. Sensitivity analyses were conducted to examine the robustness of analysis assumptions. RESULTS: Among 5882 patients, 308 deaths occurred. The hazard ratio (HR) for neurocART use was 0.89 (P=0.35) when data were stratified by cohort and adjusted for age, mode of HIV exposure, hepatitis B virus coinfection, AIDS-defining illness, CD4 count (cells/µL) and regimen count. Sensitivity analyses showed similar nonsignificant results. We also examined a composite endpoint of AIDS-defining illness or death (HR=0.93; P=0.61), baseline regimen as neurocART (HR=0.95; P=0.69), CPE category (P=0.71) and prior neurocART duration (P=0.16). No association between CD4 cell count and neurocART use was observed (P=0.52). CONCLUSIONS: Our findings do not show a significant overall survival benefit associated with neurocART compared with cART. The potential benefit associated with neurocART in terms of prevention of neurocognitive impairment did not translate into an improvement in overall survival in this population. These findings were limited by the low incidence of associated mortality. Further studies and more extensive data are needed to address these limitations.
Subject(s)
AIDS Dementia Complex/prevention & control , Anti-HIV Agents/pharmacokinetics , Central Nervous System/drug effects , HIV Infections/drug therapy , HIV Infections/mortality , AIDS Dementia Complex/mortality , Adult , Anti-HIV Agents/therapeutic use , Australia/epidemiology , CD4 Lymphocyte Count , Central Nervous System/physiopathology , Drug Therapy, Combination , Female , HIV Infections/complications , HIV Infections/physiopathology , Humans , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Survival AnalysisABSTRACT
OBJECTIVE: The aim of the study was to determine the effect of nucleoside reverse transcriptase inhibitors (NRTIs) on CD4 recovery in HIV-1-infected individuals receiving long-term suppressive combination antiretroviral therapy (cART). METHODS: A retrospective cohort study was carried out. The mean time-weighted CD4 change from baseline was determined at weeks 48, 96 and 144: its associations with exposure to NRTIs were assessed using linear regression. RESULTS: One hundred and five patients were included. Their median baseline CD4 count was 225 (interquartile range 91-362) cells/microL. A trend of greater CD4 change from baseline was observed for individuals who at baseline had CD4 counts >200 cells/microL (138 vs. 113, 176 vs. 134 and 204 vs. 173 cells/microL), or were =40 years old (136 vs. 118, 182 vs. 150, 208 vs. 174) at weeks 48, 96 and 144, respectively; however, all P-values were >0.05. Lower CD4 increases were observed in patients exposed to didanosine (ddI) or a combination of ddI and stavudine, although the difference was not statistically significant. For patients that commenced cART with CD4 count =200 cells/microL, a trend towards a CD4 count response <250 cells/microL at weeks 48, 96 and 144 was observed in patients receiving zidovudine. CONCLUSION: Exposure to different NRTIs in initial cART was not significantly associated with variable rises in CD4 cell count. However, these findings need to be confirmed in larger studies.
Subject(s)
CD4-Positive T-Lymphocytes/drug effects , HIV Infections/drug therapy , HIV-1 , Reverse Transcriptase Inhibitors/therapeutic use , Adult , CD4 Lymphocyte Count , Cohort Studies , Drug Administration Schedule , Drug Therapy, Combination , Female , HIV Infections/immunology , HIV Infections/virology , Humans , Male , Middle Aged , Retrospective Studies , Time Factors , Treatment Outcome , Viral LoadABSTRACT
OBJECTIVES: Poly-l-lactic acid (PLA) injections modestly increase objectively assessed facial thickness but not facial soft tissue volume (FSTV) over 24 weeks. The durability of this response has not been well defined objectively. METHODS: HIV-infected lipoatrophic adults were randomized to four open-label PLA treatments administered every 2 weeks from week 0 (immediate group, n=50) or from week 24 (deferred group, n=50). Endpoints included FSTV assessed by computed tomography, facial lipoatrophy severity, quality of life (QoL) and safety. Analyses were by intention to treat. RESULTS: Between weeks 24 and 48, soft tissue thickness increased modestly in injection planes, at the maxillary [mean 0.9 mm; 95% confidence interval (CI) 0.3-1.5 mm; P=0.007] and base of nasal septum levels (mean 0.4 mm; 95% CI 0.1-0.8; P=0.021), but not in untreated areas (P=0.79 and P=0.24). PLA durability assessed at week 48 in immediate group participants showed a mean change in FSTV of 14 cm(3) (95% CI-1 to 29 cm(3); P=0.060) and increased tissue depth at the maxillary (P<0.0001), base of nasal septum (P<0.0001) and mandibular (P=0.0035) levels. At week 48, clinicians and patients subjectively assessed facial lipoatrophy severity as reduced in immediate participants (83 and 91%, respectively), and the Mental Health scale score of the Short Form-36 Health Survey improved significantly in immediate participants relative to deferred participants (P=0.027). Subcutaneous injection-site nodule incidence at 48 weeks was 10%. CONCLUSIONS: PLA treatment benefits were durable, with objectively assessed modest increases in facial volume and tissue thickness sustained over 48 weeks in injection planes but not in other facial areas. Improvements in some QoL domains were maintained.
Subject(s)
Face , HIV-1 , HIV-Associated Lipodystrophy Syndrome/drug therapy , Lactic Acid/administration & dosage , Polymers/administration & dosage , Adult , Cosmetic Techniques , Female , Follow-Up Studies , HIV-Associated Lipodystrophy Syndrome/psychology , Humans , Injections, Subcutaneous , Male , Polyesters , Quality of Life/psychology , Severity of Illness Index , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: The association between anal high-grade squamous intraepithelial lesion (HSIL) and anal symptoms has not been systematically investigated. METHODS: The Study of Prevention of Anal Cancer is a prospective cohort study of men who have sex with men (MSM) ≥ 35 years old in Sydney, Australia. Self-reported symptoms were collected. Anal cytology and high-resolution anoscopy were undertaken. Using baseline visit data, men negative for squamous intra-epithelial lesion (SIL) were compared with men diagnosed with composite-HSIL (cytology and/or histology). Logistic regression analyses were performed to assess the association of symptoms with HSIL. RESULTS: Among 414 MSM included (composite-HSIL (n = 231); negative for SIL (n = 183)), 306 (73.9%) reported symptom(s) within the last 6 months. There was no association between any symptom and composite-HSIL. A significant association between anal lump and a larger burden of HSIL (at least 2 intra-anal octants) (anal lump within last month: p = 0.014; anal lump within last 6 months: p = 0.010) became non-significant after adjusting for HIV-status and recent anal warts (anal lump within last month: p = 0.057; anal lump within last 6 months: p = 0.182). CONCLUSIONS: Among MSM age 35 years and older, most anal symptoms are not a useful marker of anal HSIL.
Subject(s)
Anal Canal/pathology , Homosexuality, Male , Papillomavirus Infections/complications , Squamous Intraepithelial Lesions/etiology , Adult , Anus Neoplasms/diagnosis , Anus Neoplasms/etiology , Anus Neoplasms/prevention & control , Australia , Female , Humans , Male , Middle Aged , Prospective Studies , Squamous Intraepithelial Lesions/complications , Squamous Intraepithelial Lesions/diagnosisABSTRACT
We performed a retrospective review of cases of human immunodeficiency virus-associated progressive multifocal leucoencephalopathy in four hospitals (three in Australia and one in Hong Kong) between 1987 and 2003 in order to describe the local experience with this disease and to evaluate parameters impacting upon survival. Eighty-seven cases were identified and demographic details, baseline parameters and treatment methods and response were described. Survival was substantially increased in the post-highly active antiretroviral therapy (HAART) era with a median survival increase from 14 to 64 weeks. On multivariate analysis, variables associated with prolonged survival included a CD4 count of >100 cells/mul at diagnosis and the use of HAART post-diagnosis, with no significant additional advantage from the use of neuroactive antiretrovirals.