Liviana Calzavara

Effect of Early versus Deferred Antiretroviral Therapy for HIV on Survival

BACKGROUND The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain. METHODS We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group). RESULTS In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001). CONCLUSIONS The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.

Late Presentation for Human Immunodeficiency Virus Care in the United States and Canada

BACKGROUND. Initiatives to improve early detection and access to human immunodeficiency virus (HIV) services have increased over time. We assessed the immune status of patients at initial presentation for HIV care from 1997 to 2007 in 13 US and Canadian clinical cohorts. METHODS. We analyzed data from 44,491 HIV-infected patients enrolled in the North American-AIDS Cohort Collaboration on Research and Design. We identified first presentation for HIV care as the time of first CD4(+) T lymphocyte (CD4) count and excluded patients who prior to this date had HIV RNA measurements, evidence of antiretroviral exposure, or a history of AIDS-defining illness. Trends in mean CD4 count (measured as cells/mm(3)) and 95% confidence intervals were determined using linear regression adjusted for age, sex, race/ethnicity, HIV transmission risk, and cohort. RESULTS. Median age at first presentation for HIV care increased over time (range, 40-43 years; P < .01), whereas the percentage of patients with injection drug use HIV transmission risk decreased (from 26% to 14%; P < .01) and heterosexual transmission risk increased (from 16% to 23%; P < .01). Median CD4 count at presentation increased from 256 cells/mm(3) (interquartile range, 96-455 cells/mm(3)) to 317 cells/mm(3) (interquartile range, 135-517 cells/mm(3)) from 1997 to 2007 (P < .01). The percentage of patients with a CD4 count > or = 350 cells/mm(3) at first presentation also increased from 1997 to 2007 (from 38% to 46%; P < .01). The estimated adjusted mean CD4 count increased at a rate of 6 cells/mm(3) per year (95% confidence interval, 5-7 cells/mm(3) per year). CONCLUSION. CD4 count at first presentation for HIV care has increased annually over the past 11 years but has remained <350 cells/mm(3), which suggests the urgent need for earlier HIV diagnosis and treatment.

Intimate partner violence is associated with incident HIV infection in women in Uganda

Objectives:To quantify the association between intimate partner violence (IPV) and incident HIV infection in women in the Rakai Community Cohort Study between 2000 and 2009. Design and methods:Data were from the Rakai Community Cohort Study annual surveys between 2000 and 2009. Longitudinal data analysis was used to estimate the adjusted incidence rate ratio (IRR) of incident HIV associated with IPV in sexually active women aged 15–49 years, using a multivariable Poisson regression model with random effects. The population attributable fraction was calculated. Putative mediators were assessed using Baron and Kennys criteria and the Sobel–Goodman test. Results:Women who had ever experienced IPV had an adjusted IRR of incident HIV infection of 1.55 (95% CI 1.25–1.94, P = 0.000), compared with women who had never experienced IPV. Risk of HIV infection tended to be greater for longer duration of IPV exposure and for women exposed to more severe and more frequent IPV. The adjusted population attributable fraction of incident HIV attributable to IPV was 22.2% (95% CI 12.5–30.4). There was no evidence that either condom use or number of sex partners in the past year mediated the relationship between IPV and HIV. Conclusion:IPV is associated with incident HIV infection in a population-based cohort in Uganda, although the adjusted population attributable fraction is modest. The prevention of IPV should be a public health priority, and could contribute to HIV prevention.

Increases in HIV incidence among men who have sex with men undergoing repeat diagnostic HIV testing in Ontario, Canada.

ObjectiveTo estimate HIV incidence density for different exposure categories among people undergoing repeat testing in Ontario, Canada. MethodsPersons using voluntary, diagnostic HIV testing at least twice were identified by computerized and manual record linkage. In the 1992–2000 period, 980 seroconverters and 340 994 repeat negative testers contributed 936 145 person years (PY) of observation. Incidence density (ID) was calculated according to Kitayaporn et al.. Poisson regression was used to evaluate differences in incidence. ResultsAmong men who have sex with men (MSM), ID declined between 1992–1996, from 1.23 per 100 PY in 1992 to 0.79 per 100 PY in 1996 [relative risk (RR), 0.86 per year; 95% confidence interval (CI), 0.77–0.96]. Subsequently, ID increased to 1.39 per 100 PY in 1999 (RR, 1.18 per year; 95% CI, 1.05–1.34). In 2000, ID was 1.16 per 100 PY but this decrease was not statistically significantly different from 1999. MSM in their twenties had the highest ID in 1992–1996, but in 1996–2000 MSM in their thirties had the highest risk of infection. Among injecting drug users (IDU), ID decreased from 0.64 per 100 PY in 1992 to 0.14 per 100 PY in 2000 (RR, 0.87 per year; 95% CI, 0.80–0.94). Among heterosexuals, annual incidence remained constant at about 0.03 per 100 PY in 1992–2000. ConclusionsIncreases in ID were identified among MSM from 1996 to 1999. These findings are consistent with other research. Continued vigilance and improved surveillance are needed to better understand and control the epidemic.

Prevalence of HIV and hepatitis C virus infections among inmates of Ontario remand facilities

Background: Each year more than 56 000 adult and young offenders are admitted to Ontarios remand facilities (jails, detention centres and youth centres). The prevalence of HIV infection in Ontario remand facilities was last measured over a decade ago, and no research on the prevalence of hepatitis C virus (HCV) infection has been conducted in such facilities. We sought to determine the prevalence of HIV infection, HCV infection and HIV–HCV coinfection among inmates in Ontarios remand facilities. Methods: A voluntary and anonymous cross-sectional prevalence study of HIV and HCV infections was conducted among people admitted to 13 selected remand facilities across Ontario between Feb. 1, 2003, and June 20, 2004. Data collection included a saliva specimen for HIV and HCV antibody screening and an interviewer-administered survey. Prevalence rates and 95% confidence intervals were calculated and examined according to demographic characteristics, region of incarceration and self-reported history of injection drug use. Results: In total, 1877 participants provided both a saliva specimen and survey information. Among the adult participants, the prevalence of HIV infection was 2.1% among men and 1.8% among women. Adult offenders most likely to have HIV infection were older offenders (≥ 30 years) and injection drug users. The prevalence of HCV infection was 15.9% among men, 30.2% among women and 54.7% among injection drug users. Adult offenders most likely to have HCV infection were women, older offenders (≥ 30 years) and injection drug users. The prevalence of HCV–HIV coinfection was 1.2% among men and 1.5% among women. It was highest among older inmates and injection drug users. Among the young offenders, none was HIV positive and 1 (0.4%) was HCV positive. On the basis of the study results, we estimated that 1079 HIV-positive adults and 9208 HCV-positive adults were admitted to remand facilities in Ontario from Apr. 1, 2003, to Mar. 31, 2004. Interpretation: Adult offenders entering Ontario remand facilities have a considerably higher prevalence of HIV and HCV infections than the general population.

Experiences of and responses to HIV among African and Caribbean communities in Toronto, Canada

Abstract African and Caribbean communities in Canada and other developed countries are disproportionately affected by HIV/AIDS. This qualitative study of African and Caribbean communities in Toronto sought to understand HIV-related stigma, discrimination, denial and fear, and the effects of multiple intersecting factors that influence responses to the disease, prevention practices and access to treatment and support services. Semi-structured interviews were conducted with 30 HIV-positive men and women and focus groups were conducted with 74 men and women whose HIV status was negative or unknown. We identified a range of issues faced by African and Caribbean people that may increase the risk for HIV infection, create obstacles to testing and treatment and lead to isolation of HIV-positive people. Our findings suggest the need for greater sensitivity and knowledge on the part of healthcare providers; more culturally specific support services; community development; greater community awareness; and expanded efforts to tackle housing, poverty, racism and settlement issues.

Trends in Multidrug Treatment Failure and Subsequent Mortality among Antiretroviral Therapy-Experienced Patients with HIV Infection in North America

BACKGROUND Although combination antiretroviral therapy continues to evolve, with potentially more effective options emerging each year, the ability of therapy to prevent multiple regimen failure and mortality in clinical practice remains poorly defined. METHODS Sixteen cohorts representing over 60 sites contributed data on all individuals who initiated combination antiretroviral therapy. We identified those individuals who experienced virologic failure (defined as a human immunodeficiency virus [HIV] RNA level >1000 copies/mL), received modified therapy, and subsequently had a second episode of virologic failure. Multivariate Cox regression was used to assess factors associated with time to second regimen failure and the time to death after the onset of second regimen failure. RESULTS Of the 42,790 individuals who received therapy, 7159 experienced a second virologic failure. The risk of second virologic failure decreased from 1996 (56 cases per 100 person-years) through 2005 (16 cases per 100 person-years; P < .001). The cumulative mortality after onset of second virologic failure was 26% at 5 years and decreased over time. A history of AIDS, a lower CD4(+) T cell count, and a higher plasma HIV RNA level were each independently associated with mortality. Similar trends were observed when analysis was limited to the subset of previously treatment-naive patients CONCLUSIONS Although the rates of multiple regimen failure have decreased dramatically over the past decade, mortality rates for those who have experienced failure of at least 2 regimens have remained high. Plasma HIV RNA levels, CD4(+) T cell counts at time of treatment failure, and a history of AIDS remain independent risk factors for death, which emphasizes that these factors remain important targets for those in need of more-aggressive therapeutic interventions.

A systematic review of the relationships between intimate partner violence and HIV/AIDS.

Background Intimate partner violence (IPV) is a significant health problem that has been associated with HIV infection in numerous studies. We aimed to systematically review the literature on relationships between IPV and HIV in order to describe the prevalence of IPV in people with HIV, the prevalence of HIV in people experiencing IPV, the association between IPV and HIV, and evidence regarding mechanisms of risk and interventions. Methods Data sources were 10 electronic databases and reference lists. Studies were included if they reported data on the relationship between IPV and HIV. All records were independently reviewed by two authors at the stages of title and abstract review and full text review. Any abstract considered eligible by either reviewer was reviewed in full, and any disagreement regarding eligibility of full texts or data extracted was resolved by discussion. Results 101 articles were included. Experiencing IPV and HIV infection were associated in unadjusted analyses in most studies, as well as in adjusted analyses in many studies. The findings of qualitative and quantitative studies assessing potential mechanisms linking IPV and HIV were variable. Few interventions have been assessed, but two identified in this review were promising in terms of preventing IPV, though not HIV infection. Conclusions Experiencing IPV and HIV infection tend to be associated in unadjusted analyses, suggesting that IPV screening and linkage with relevant programs and services may be valuable. It is unclear whether there is a causal association between experiencing IPV and HIV infection. Research should focus on defining parameters of IPV which are relevant to HIV infection, including type of IPV and period of exposure and risk, on assessing potential mechanisms, and on developing and assessing interventions which build on the strengths of existing studies.

Using serial observations to identify predictors of progression to aids in the Toronto Sexual Contact Study

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of an emerging heterosexual HIV epidemic in Russia.

Background: The Russian Federation is currently experiencing one of the fastest growing HIV epidemics worldwide. The objective was to identify sexual risk factors for recent heterosexually-acquired HIV infections. Methods: A case-control study of recent HIV infection was conducted in the regions of Altaiskiy Krai, Krasnoyarskiy Krai, Saratov Oblast, and Tverskaya Oblast. Data from 166 participants who did not report recent injection drug use were analyzed (19 male cases, 22 male controls, 67 female cases, 58 female controls). Independent risk factors for HIV infection are reported as adjusted odds ratios (AOR) with 95% confidence intervals (CI). Results: Risk factors were unprotected sex with an HIV-positive/status unknown regular partner (among women only: AOR 5.4, 95% CI 2.1–13); a regular sexual partner who was an injection drug user (AOR 3.6, 95% CI 1.5–8.5); 5 or more sexual partners (among men only: AOR 2.7, 95% CI 0.66–11); unprotected sex with a partner who had a diagnosed sexually transmitted infection (STI) or signs/symptoms of an STI (AOR 6.4, 95% CI 1.1–38); and undiagnosed signs/symptoms of an STI (AOR 3.4, 95% CI 1.5–7.6). Conclusions: These data provide evidence of bridging between the injecting and noninjecting populations. Concomitant STI seem to have a major role in fueling the Russian HIV epidemic.