The objective of this study was to examine supervised injecting facility (SIF) use among a cohort of 395 HIV-positive injection drug users (IDUs) in Vancouver, Canada. The correlates of SIF use were identified using generalized estimating equation analyses. In multivariate analyses, frequent SIF use was associated with homelessness (adjusted odds ratio [AOR] = 1.90), daily heroin injection (AOR = 1.56), and daily cocaine injection (AOR = 1.59). The reasons given for not using the SIF included a preference for injecting at home and already having a safe place to inject. The SIF services most commonly used were needle exchange and nursing services. The SIF appears to have attracted a high-risk subpopulation of HIV-positive IDUs; this coverage perhaps could be extended with the addition of HIV- specific services such as disease monitoring and the provision of antiretroviral therapy.
Individuals of Asian heritage represent the largest ethnic minority in Canada. Approximately 10% of the new HIV diagnoses in men in British Columbia occur among Asian-Canadians. However, the HIV risk patterns of Asian men who have sex with men (MSM) have not been extensively studied.
Participants aged ≥ 19 years were enrolled in a venue-based HIV serobehavioural survey of MSM in Vancouver, Canada. We compared the demographic characteristics, risk behaviours, and prevalence of HIV and other sexual and blood borne infections between Asian and non-Asian MSM using bivariate analysis and logistic regression confounder modelling.
Amongst 1132 participants, 110 (9.7%) self-identified as Asian. Asian participants were younger than non-Asian participants (median age 29 vs. 32 years; p < 0.001), but otherwise did not differ from other study participants. HIV prevalence was lower among Asian MSM compared to Non-Asian MSM (3.7% vs 19.0%, p <0.001). Among men who self-reported as HIV negative or unknown we found no differences in unprotected anal intercourse (UAI) with a discordant or unknown serostatus partner in the previous six months (11 vs. 13%; p = 0.503). However, Asian MSM were less likely to report ever using injection drugs (10.8% vs. 19.2%; p = 0.043) or using alcohol before having sex (52% vs. 64.4%; p = 0.017).
Asian MSM in our study reported similar rates of UAI as non-Asian MSM, but had a lower prevalence of HIV infection. Other factors, such as the use of drugs and alcohol, in relation to sex, may partly explain these differences. However this requires further investigation.
HIV; Homosexuality; Men who have sex with men; Asian
Food insecurity is increasingly recognized as a barrier to optimal treatment outcomes but there is little data on this issue. We assessed associations between food insecurity and mortality in HIV-infected antiretroviral therapy (ART)-treated individuals in Vancouver, British Columbia (BC), and whether body max index (BMI) modified associations.
Individuals were recruited from the BC HIV/AIDS drug treatment program in 1998 and 1999, and were followed until June 2007 for outcomes. Food insecurity was measured with the Radimer/Cornell questionnaire. Cox proportional hazard models were used to determine associations between food insecurity, BMI and non-accidental deaths when controlling for confounders.
Among 1119 participants, 536 (48%) were categorized as food insecure and 160 (14%) were categorized as underweight (BMI <18.5). After a median follow-up time of 8.2 years, 153 individuals (14%) had died from non-accidental deaths. After controlling for adherence, CD4 counts, and socioeconomic variables, people who were food insecure and underweight were nearly two times more likely to die (Adjusted hazard ratio [AHR]=1.94, 95% Confidence interval [CI]=1.10-3.40) compared with people who were not food insecure or underweight. There was also a trend towards increased risk of mortality among people who were food insecure and not underweight (AHR= 1.40, 95% CI=0.91-2.05). In contrast, people who were underweight but food secure were not more likely to die.
Food insecurity is a risk factor for mortality among ART-treated individuals in BC, particularly among individuals who are underweight. Innovative approaches to address food insecurity should be incorporated into HIV treatment programs.
Food insecurity; HIV/AIDS; mortality; Vancouver
Little is known about the potential impact of food insecurity on mortality among people living with HIV/AIDS. We examined the potential relationship between food insecurity and all-cause mortality among HIV-positive injection drug users (IDU) initiating antiretroviral therapy (ART) across British Columbia (BC).
Cross-sectional measurement of food security status was taken at participant ART initiation. Participants were prospectively followed from June 1998 to September 2011 within the fully subsidized ART program. Cox proportional hazard models were used to ascertain the association between food insecurity and mortality, controlling for potential confounders.
Among 254 IDU, 181 (71.3%) were food insecure and 108 (42.5%) were hungry. After 13.3 years of median follow-up, 105 (41.3%) participants died. In multivariate analyses, food insecurity remained significantly associated with mortality (adjusted hazard ratio [AHR] = 1.95, 95% CI: 1.07–3.53), after adjusting for potential confounders.
HIV-positive IDU reporting food insecurity were almost twice as likely to die, compared to food secure IDU. Further research is required to understand how and why food insecurity is associated with excess mortality in this population. Public health organizations should evaluate the possible role of food supplementation and socio-structural supports for IDU within harm reduction and HIV treatment programs.
Many people living with HIV in sub-Saharan Africa desire biological children. Implementation of HIV prevention strategies that support the reproductive goals of people living with HIV while minimizing HIV transmission risk to sexual partners and future children requires a comprehensive understanding of pregnancy in this population. We analyzed prospective cohort data to determine pregnancy incidence and predictors among HIV-positive women initiating antiretroviral therapy (ART) in a setting with high HIV prevalence and fertility.
Participants were enrolled in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort of HIV-positive individuals initiating ART in Mbarara. Bloodwork (including CD4 cells/mm3, HIV viral load) and questionnaires (including socio-demographics, health status, sexual behavior, partner dynamics, HIV history, and self-reported pregnancy) were completed at baseline and quarterly. Our analysis includes 351 HIV-positive women (18–49 years) who enrolled between 2005–2011. We measured pregnancy incidence by proximal and distal time relative to ART initiation and used multivariable Cox proportional hazards regression analysis (with repeated events) to identify baseline and time-dependent predictors of pregnancy post-ART initiation.
At baseline (pre-ART initiation), median age was 33 years [IQR: 27–37] and median prior livebirths was four [IQR: 2–6]. 38% were married with 61% reporting HIV-positive spouses. 73% of women had disclosed HIV status to a primary sexual partner. Median baseline CD4 was 137 cells/mm3 [IQR: 81–207]. At enrolment, 9.1% (31/342) reported current pregnancy. After ART initiation, 84 women experienced 105 pregnancies over 3.8 median years of follow-up, yielding a pregnancy incidence of 9.40 per 100 WYs. Three years post-ART initiation, cumulative probability of at least one pregnancy was 28% and independently associated with younger age (Adjusted Hazard Ratio (AHR): 0.89/year increase; 95%CI: 0.86–0.92) and HIV serostatus disclosure to primary sexual partner (AHR: 2.45; 95%CI: 1.29–4.63).
Nearly one-third of women became pregnant within three years of initiating ART, highlighting the need for integrated services to prevent unintended pregnancies and reduce periconception-related risks for HIV-infected women choosing to conceive. Association with younger age and disclosure suggests a role for early and couples-based safer conception counselling.
Previous studies of adherence to antiretroviral therapy (ART) for HIV among young injection drug users (IDU) have been limited because financial barriers to care disproportionately affect youth, thus confounding results. This study examines adherence among IDU in a unique setting where all medical care is provided free-of-charge. From May 1996 to April 2008, we followed a prospective cohort of 545 HIV-positive IDU of 18 years of age or older in Vancouver, Canada. Using generalized estimating equations (GEE), we studied the association between age and adherence (obtaining ART≥95% of the prescribed time), controlling for potential confounders. Using Cox proportional hazards regression, we also studied the effect of age on time to viral load suppression (<500 copies per milliliter), and examined adherence as a mediating variable. Five hundred forty-five participants were followed for a median of 23.8 months (interquartile range [IQR]=8.5–91.6 months). Odds of adherence were significantly lower among younger IDU (adjusted odds ratio [AOR]=0.76 per 10 years younger; 95% confidence interval [CI], 0.65–0.89). Younger IDU were also less likely to achieve viral load suppression (adjusted hazard ratio [AHR]=0.75 per 10 years younger; 95% CI, 0.64–0.88). Adding adherence to the model eliminated this association with age, supporting the role of adherence as a mediating variable. Despite absence of financial barriers, younger IDU remain less likely to adhere to ART, resulting in inferior viral load suppression. Interventions should carefully address the unique needs of young HIV-positive IDU.
Evidence is needed to improve HIV treatment outcomes for individuals who use injection drugs (IDU). Although studies have suggested higher rates of plasma viral load (PVL) rebound among IDU on antiretroviral therapy (ART), risk factors for rebound have not been thoroughly investigated.
We used data from a long-running community-recruited prospective cohort of IDU in Vancouver, Canada, linked to comprehensive ART and clinical monitoring records. Using proportional hazards methods, we modeled the time to confirmed PVL rebound above 1000 copies/mL among IDU on ART with sustained viral suppression, defined as two consecutive undetectable PVL measures.
Between 1996 and 2009, 277 individuals had sustained viral suppression. Over a median follow-up of 32 months, 125 participants (45.1%) experienced at least one episode of virologic failure for an incidence of 12.6 (95% Confidence Interval [CI]: 10.5 – 15.0) per 100 person years. In a multivariate model, PVL rebound was independently associated with sex trade involvement (Adjusted Hazard Ratio [AHR] = 1.40, 95% CI: 1.08 – 1.82) and recent incarceration (AHR = 1.83, 95% CI: 1.33 – 2.52). Methadone maintenance therapy (AHR = 0.79, 95% CI: 0.66 – 0.94) was protective. No measure of illicit drug use was predictive.
In this setting of free ART, several social and environmental factors predicted higher risks of viral rebound among IDU, including sex trade involvement and incarceration. These findings should help inform efforts to identify individuals at risk of viral rebound as well as targeted interventions to treat and retain individuals in effective ART.
human immunodeficiency virus (HIV) infection; antiretroviral therapy (ART); injection drug user (IDU); plasma HIV-1 RNA viral load; viral suppression; viral rebound
To characterize the impact of longitudinal adherence on survival in drug-naive individuals starting currently recommended highly active antiretroviral therapy (HAART) regimens.
Eligible study participants initiated HAART between January 2000 and November 2004 and were followed until November 2005 (N = 903). HAART regimens contained efavirenz, nevirapine, or ritonavir-boosted atazanavir or lopinavir. Marginal structural modeling was used to address our objective.
The all-cause mortality was 11%. Individual adherence decreased significantly over time, with the mean adherence shifting from 79% within the first 6 months of starting HAART to 72% within the 24- to 30-month period (P value < 0.01). Nonadherence over time (<95%) was strongly associated with higher risk of mortality (hazard ratio: 3.13; 95% confidence interval (CI): 1.95 to 5.05). Nonadherent (<95%) patients on nonnucleoside reverse transcriptase inhibitor (NNRTI)–based and boosted protease inhibitor–based regimens were, respectively, 3.61 times (95% CI: 2.15 to 6.06) and 3.25 times (95% CI: 1.63 to 6.49) more likely to die than adherent patients. Within the NNRTI-based regimens, nonadherent individuals on efavirenz were at a higher risk of mortality.
Incomplete adherence to modern HAART over time was strongly associated with increased mortality, and patients on efavirenz-based NNRTI therapies were particularly at a higher risk if nonadherent. These results highlight the need to develop further strategies to help sustain high levels of adherence on a long-term basis.
adherence; boosted PI; HAART; marginal structural models; mortality; NNRTI
The objective of this study was to develop a reliable HAART optimism scale among HIV-positive women in Uganda and to test the scale’s validity against measures of fertility intentions, sexual activity, and unprotected sexual intercourse. We used cross-sectional survey data of 540 women (18–50 years) attending Mbarara University’s HIV clinic in Uganda. Women were asked how much they agreed or disagreed with 23 statements about HAART. Data were subjected to a principal components and factor analyses. Subsequently, we tested the association between the scale and fertility intentions and sexual behaviour using Wilcoxon rank sum test. Factor analysis yielded three factors, one of which was an eight-item HAART optimism scale with moderately high internal consistency (α = 0.70). Women who reported that they intended to have (more) children had significantly higher HAART optimism scores (median = 13.5 [IQR: 12–16]) than women who did not intend to have (more) children (median = 10.5 [IQR: 8–12]; P <0.0001). Similarly, women who were sexually active and who reported practicing unprotected sexual intercourse had significantly higher HAART optimism scores than women who were sexually abstinent or who practiced protected sexual intercourse. Our reliable and valid scale, termed the Women’s HAART Optimism Monitoring and EvaluatioN scale (WHOMEN’s scale), may be valuable to broader studies investigating the role of HAART optimism on reproductive intentions and sexual behaviours of HIV-positive women in high HIV prevalence settings.
HIV; HAART; Uganda; Scale; HAART optimism; Women; Fertility intentions; Sexual behaviour; HAART optimism scale
To assess the association between antiretroviral therapy (ART) and fertility history and desire among HIV-positive Ugandan women, we conducted a cross-sectional study among HIV-positive Ugandan women aged 18–50 years who attended an HIV clinic at Mbarara University in western Uganda between November 1, 2005 and June 6, 2006. Of 538 women approached, 501 were enrolled. ART use was associated with increased odds of fertility desire (AOR 2.99, 95% CI 1.38–6.28), and decreased odds of pregnancy (AOR 0.56, 95% CI 0.33–0.95) and live birth (AOR 0.30, 95% CI 0.13–0.66). ART was associated with an increase in fertility desire, but was not associated with an increase in fertility. Additional studies will be needed to determine if this greater fertility desire among ART-treated women leads to an increase in fertility as ART use expands.
Uganda; Fertility; HIV/AIDS; Fertility desires; Antiretroviral therapy
To investigate the relationship between HIV-1 drug resistance and adherence and the accumulation rate of resistance mutations in 1191 HIV-infected, antiretroviral-naive adults initiating highly active antiretroviral therapy in British Columbia, Canada.
Plasma samples with plasma viral load >1000 copies per milliliter collected within 30 months of follow-up were genotyped for drug resistance. Adherence was estimated using prescription refills and plasma drug levels. The primary outcome measure was time to detection of drug resistance. Cox proportional hazard regression was used to calculate hazard ratios (HRs) associated with baseline variables.
The accumulation rates of multiple primary and secondary mutations were similar in patients initiating highly active antiretroviral therapy with protease inhibitor versus nonnucleoside reverse transcriptase inhibitor (NNRTI). Rates decreased approximately 50% per additional mutation. At 80%–90% adherence based on refills, there was greater risk of detecting lamivudine (3TC) [HR 3.0, 95% confidence interval (CI): 1.9 to 4.7; P < 0.0001] and NNRTI mutations (HR 6.0, 95% CI: 3.3 to 10.9; P < 0.0001) compared with the ≥95% refill reference group. In a multivariate model, individuals with <95% refills and consistently detectable plasma drug levels were at increased risk for 3TC (HR 4.5, 95% CI: 2.6 to 7.9; P = 0.0001) and NNRTI resistance (HR 7.0, 95% CI: 3.4 to 14.5; P = 0.0001) compared with the reference group of ≥95% refills with consistently detectable drug levels. Adherence–resistance relationships were much weaker for protease inhibitors and nucleoside reverse transcriptase inhibitors as there was little variance in HRs among the different adherence strata compared with 3TC and NNRTIs.
The relationships between resistance, adherence, and mutation accumulation differ between HIV drug classes.
adherence; HAART; HIV-1 drug resistance; mutations
To define a population-level cohort of individuals infected with the human immunodeficiency virus (HIV) in the province of British Columbia from available registries and administrative datasets using a validated case-finding algorithm.
Individuals were identified for possible cohort inclusion from the BC Centre for Excellence in HIV/AIDS (CfE) drug treatment program (antiretroviral therapy) and laboratory testing datasets (plasma viral load (pVL) and CD4 diagnostic test results), the BC Centre for Disease Control (CDC) provincial HIV surveillance database (positive HIV tests), as well as databases held by the BC Ministry of Health (MoH); the Discharge Abstract Database (hospitalizations), the Medical Services Plan (physician billing) and PharmaNet databases (additional HIV-related medications). A validated case-finding algorithm was applied to distinguish true HIV cases from those likely to have been misclassified. The sensitivity of the algorithms was assessed as the proportion of confirmed cases (those with records in the CfE, CDC and MoH databases) positively identified by each algorithm. A priori hypotheses were generated and tested to verify excluded cases.
A total of 25,673 individuals were identified as having at least one HIV-related health record. Among 9,454 unconfirmed cases, the selected case-finding algorithm identified 849 individuals believed to be HIV-positive. The sensitivity of this algorithm among confirmed cases was 88%. Those excluded from the cohort were more likely to be female (44.4% vs. 22.5%; p<0.01), had a lower mortality rate (2.18 per 100 person years (100PY) vs. 3.14/100PY; p<0.01), and had lower median rates of health service utilization (days of medications dispensed: 9745/100PY vs. 10266/100PY; p<0.01; days of inpatient care: 29/100PY vs. 98/100PY; p<0.01; physician billings: 602/100PY vs. 2,056/100PY; p<0.01).
The application of validated case-finding algorithms and subsequent hypothesis testing provided a strong framework for defining a population-level cohort of HIV infected people in BC using administrative databases.
The U.S. National HIV/AIDS Strategy targets for 2015 include increasing access to care and improving health outcomes for persons living with HIV in the United States (PLWH-US).
To demonstrate the utility of the NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) for monitoring trends in the HIV epidemic in the United States and to present trends in HIV treatment and related health outcomes.
Trends from annual cross-sectional analyses comparing patients from pooled, multicenter, prospective, clinical HIV cohort studies with PLWH-US, as reported to national surveillance systems in 40 states.
U.S. HIV outpatient clinics.
HIV-infected adults with 1 or more HIV RNA plasma viral load (HIV VL) or CD4 T-lymphocyte (CD4) cell count measured in any calendar year from 1 January 2000 to 31 December 2008.
Annual rates of antiretroviral therapy use, HIV VL, and CD4 cell count at death.
45 529 HIV-infected persons received care in an NA-ACCORD–participating U.S. clinical cohort from 2000 to 2008. In 2008, the 26 030 NA-ACCORD participants in care and the 655 966 PLWH-US had qualitatively similar demographic characteristics. From 2000 to 2008, the proportion of participants prescribed highly active antiretroviral therapy increased by 9 percentage points to 83% (P < 0.001), whereas the proportion with suppressed HIV VL (≤2.7 log10 copies/mL) increased by 26 percentage points to 72% (P < 0.001). Median CD4 cell count at death more than tripled to 0.209 × 109 cells/L (P < 0.001).
The usual limitations of observational data apply.
The NA-ACCORD is the largest cohort of HIV-infected adults in clinical care in the United States that is demographically similar to PLWH-US in 2008. From 2000 to 2008, increases were observed in the percentage of prescribed HAART, the percentage who achieved a suppressed HIV VL, and the median CD4 cell count at death.
Primary Funding Source
National Institutes of Health, Centers for Disease Control and Prevention, Canadian Institutes of Health Research, Canadian HIV Trials Network, and the government of British Columbia, Canada.
We aimed to characterize changes in patterns of new HIV diagnoses, HIV-related mortality, and HAART use in Canada from 1995 to 2008.
Data on new HIV diagnoses were obtained from Health Canada, HIV-related mortality statistics were obtained from Statistics Canada, and information on the number of people on HAART was obtained from the single antiretroviral distribution site in British Columbia (BC), and the Intercontinental Marketing Services Health for Ontario and Quebec. Trends of new HIV-positive tests were assessed using Spearman rank correlations and the association between the number of individuals on HAART and new HIV diagnoses were estimated using generalized estimating equations (GEE).
A total of 34,502 new HIV diagnoses were observed. Rates of death in BC are higher than those in Ontario and Quebec with the rate being 2.03 versus 1.06 and 1.21 per 100,000 population, respectively. The number of HIV infected individuals on HAART increased from 5,091 in 1996 to 20,481 in 2008 in the three provinces (4 fold increase). BC was the only province with a statistically significant decrease (trend test p<0.0001) in the rate of new HIV diagnoses from 18.05 to 7.94 new diagnoses per 100,000 population. Our analysis showed that for each 10% increment in HAART coverage the rate of new HIV diagnoses decreased by 8% (95% CI: 2.4%, 13.3%)
Except for British Columbia, the number of new HIV diagnoses per year has remained relatively stable across Canada over the study period. The decline in the rate of new HIV diagnoses per year may be in part attributed to the greater expansion of HAART coverage in this province.
Background. HIV-infected women are disproportionately burdened by gynaecological complications, psychological disorders, and certain sexually transmitted infections that may not be adequately addressed by HIV-specific care. We estimate the prevalence and covariates of women's health care (WHC) utilization among harder-to-reach, treatment-experienced HIV-infected women in British Columbia (BC), Canada. Methods. We used survey data from 231 HIV-infected, treatment-experienced women enrolled in the Longitudinal Investigations into Supportive and Ancillary Health Services (LISA) study, which recruited harder-to-reach populations, including aboriginal people and individuals using injection drugs. Independent covariates of interest included sociodemographic, psychosocial, behavioural, individual health status, structural factors, and HIV clinical variables. Logistic regression was used to generate adjusted estimates of associations between use of WHC and covariates of interest.
Results. Overall, 77% of women reported regularly utilizing WHC. WHC utilization varied significantly by region of residence (P value <0.01). In addition, women with lower annual income (AOR (95% CI) = 0.14 (0.04–0.54)), who used illicit drugs (AOR (95% CI) = 0.42 (0.19–0.92)) and who had lower provider trust (AOR (95% CI) = 0.97 (0.95–0.99)), were significantly less likely to report using WHC. Conclusion. A health service gap exists along geographical and social axes for harder-to-reach HIV-infected women in BC. Women-centered WHC and HIV-specific care should be streamlined and integrated to better address women's holistic health.
We developed and validated a new and simple metric, the Programmatic Compliance Score (PCS), based on the IAS-USA antiretroviral therapy management guidelines for HIV-infected adults, as a predictor of all-cause mortality, at a program-wide level. We hypothesized that non-compliance would be associated with the highest probability of mortality.
Methods and Findings
3543 antiretroviral-naive HIV-infected patients aged ≥19 years who initiated antiretroviral therapy between January 1, 2000 and August 31, 2009 in British Columbia (BC), Canada, were followed until August 31, 2010. The PCS is composed by six non-performance indicators based on the IAS-USA guidelines: (1) having <3 CD4 count tests in the first year after starting antiretroviral therapy; (2) having <3 plasma viral load tests in the first year after starting antiretroviral therapy; (3) not having drug resistance testing done prior to starting antiretroviral therapy; (4) starting on a non-recommended antiretroviral therapy regimen; (5) starting therapy with CD4 <200 cells/mm3; and (6) not achieving viral suppression within 6 months since antiretroviral therapy initiation. The sum of these six indicators was used to develop the PCS score - higher score indicates poorer performance. The main outcome was all-cause mortality. Each PCS component was independently associated with mortality. In the mortality analysis, the odds ratio (OR) for PCS ≥4 versus 0 was 22.37 (95% CI 10.46–47.84).
PCS was strongly associated with all-cause mortality. These results lend independent validation to the IAS-USA treatment guidelines for HIV-infected adults. Further efforts are warranted to enhance the PCS as a means to further improve clinical outcomes. These should be specifically evaluated and targeted at healthcare providers and patients.
The generalizability of antiretroviral therapy (ART) clinical trial efficacy findings to routine care settings is not well studied. We compared the relative effectiveness of initial ART regimens estimated in AIDS Clinical Trial Group (ACTG) randomized controlled trials with that among patients receiving ART at Antiretroviral Therapy Cohort Collaboration (ART-CC) study sites.
Treatment-naive HIV-infected patients initiating identical ART regimens in ACTG trials (A5095 and A5142) and at 15 ART-CC cohort study sites were included. Virological failure (HIV-1 RNA >200 copies/ml) at 24- and 48-weeks, incident AIDS-defining events and mortality were measured according to study design (ART-CC cohort vs. ACTG trial) and stratified by 3rd drug [Abacavir (ABC), Efavirenz (EFV), and Lopinavir/r (LPV/r)]. We used logistic regression to estimate and compare odds ratios for virological failure between different regimens and study designs, and used Cox models to estimate and compare hazard ratios for AIDS and death.
Compared with patients receiving ABC, those receiving EFV had roughly half the odds of 24-week virologic failure (>200 copies/mL) in both ACTG 5095 (OR=0.53, 95% CI 0.36–0.79) and ART-CC (0.46, 0.37–0.57). Virologic superiority of EFV (vs. ABC) appeared comparable in ART-CC and ACTG 5095 (ratio of ORs 0.86, 95% CI 0.54–1.35). Odds ratios for 48-week virologic failure, comparing EFV with LPV/r, were also comparable in ACTG 5142 and ART-CC (ratio of ORs 0.87, 0.45–1.69).
Between ART regimen virologic efficacy of 3rd drugs ABC, EFV, and LPV/r observed in the ACTG 5095 and 5142 trials appear generalizable to the routine care setting of ART-CC clinical cohorts.
HIV; AIDS; Antiretroviral therapy; Comparative effectiveness; Viral load
Background. Screening for tuberculosis prior to highly active antiretroviral therapy (HAART) initiation is not routinely performed in low-incidence settings. Identifying factors associated with developing tuberculosis after HAART initiation could focus screening efforts.
Methods. Sixteen cohorts in the United States and Canada contributed data on persons infected with human immunodeficiency virus (HIV) who initiated HAART December 1995–August 2009. Parametric survival models identified factors associated with tuberculosis occurrence.
Results. Of 37845 persons in the study, 145 were diagnosed with tuberculosis after HAART initiation. Tuberculosis risk was highest in the first 3 months of HAART (20 cases; 215 cases per 100000 person-years; 95% confidence interval [CI]: 131–333 per 100000 person-years). In a multivariate Weibull proportional hazards model, baseline CD4+ lymphocyte count <200, black race, other nonwhite race, Hispanic ethnicity, and history of injection drug use were independently associated with tuberculosis risk. In addition, in a piece-wise Weibull model, increased baseline HIV-1 RNA was associated with increased tuberculosis risk in the first 3 months; male sex tended to be associated with increased risk.
Conclusions. Screening for active tuberculosis prior to HAART initiation should be targeted to persons with baseline CD4 <200 lymphocytes/mm3 or increased HIV-1 RNA, persons of nonwhite race or Hispanic ethnicity, history of injection drug use, and possibly male sex.
Determination of the prevalence of accumulated antiretroviral drug resistance among persons infected with human immunodeficiency virus (HIV) is complicated by the lack of routine measurement in clinical care. By using data from 8 clinic-based cohorts from the North American AIDS Cohort Collaboration on Research and Design, drug-resistance mutations from those with genotype tests were determined and scored using the Genotypic Resistance Interpretation Algorithm developed at Stanford University. For each year from 2000 through 2005, the prevalence was calculated using data from the tested subset, assumptions that incorporated clinical knowledge, and multiple imputation methods to yield a complete data set. A total of 9,289 patients contributed data to the analysis; 3,959 had at least 1 viral load above 1,000 copies/mL, of whom 2,962 (75%) had undergone at least 1 genotype test. Using these methods, the authors estimated that the prevalence of accumulated resistance to 2 or more antiretroviral drug classes had increased from 14% in 2000 to 17% in 2005 (P < 0.001). In contrast, the prevalence of resistance in the tested subset declined from 57% to 36% for 2 or more classes. The authors’ use of clinical knowledge and multiple imputation methods revealed trends in HIV drug resistance among patients in care that were markedly different from those observed using only data from patients who had undergone genotype tests.
antiretroviral therapy, highly active; drug resistance; genotype; HIV
To establish the reliability and validity of a shortened (10-item) depression scale used among HIV-positive patients enrolled in the Drug Treatment Program in British Columbia, Canada.
The 10-item CES-D (Center for Epidemiologic Studies Depression Scale) was examined among 563 participants who initiated antiretroviral therapy (ART) between August 1, 1996 and June 30, 2002. Internal consistency of the scale was measured by Cronbach’s alpha. Using the original CES-D 20 as primary criteria, comparisons were made using the Kappa statistic. Predictive accuracy of CES-D 10 was assessed by calculating sensitivity, specificity, positive predictive values and negative predictive values. Factor analysis was also performed to determine if the CES-D 10 contained the same factors of positive and negative affect found in the original development of the CES-D.
The correlation between the original and the shortened scale is very high (Spearman correlation coefficient = 0.97 (P<0.001). Internal consistency reliability coefficients of the CES-D 10 were satisfactory (Cronbach α = 0.88). The CES-D 10 showed comparable accuracy to the original CES-D 20 in classifying participants with depressive symptoms (Kappa = 0.82, P<0.001). Sensitivity of CES-D 10 was 91%; specificity was 92%; and positive predictive value was 92%. Factor analysis demonstrates that CES-D 10 contains the same underlying factors of positive and negative affect found in the original development of the CES-D 20.
The 10-item CES-D is a comparable tool to measure depressive symptoms among HIV-positive research participants.
(See the editorial commentary by Flanigan and Beckwith, on pages 1201–3.)
Background. Although some studies have identified impressive clinical gains for incarcerated HIV-seropositive injection drug users (IDUs) undergoing antiretroviral therapy (ART), the effect of incarceration on adherence to ART remains undetermined.
Methods. We used data from a long-term community-recruited cohort of HIV-seropositive IDUs, including comprehensive ART dispensation records, in a setting where HIV care is free. We estimated the relationship between the cumulative burden of incarceration, measured longitudinally, and the odds of <95% adherence to ART, with use of multivariate modeling.
Results. From 1996 through 2008, 490 IDUs were recruited and contributed 2220 person-years of follow-up; 271 participants (55.3%) experienced an incarceration episode, with the number of incarcerations totaling 1156. In a multivariate model, incarceration had a strong dose-dependent effect on the likelihood of nonadherence to ART: 1-2 incarceration events (adjusted odds ratio [AOR], 1.49; 95% confidence interval [95% CI], 1.03–2.05), 3–5 events (AOR, 2.48; 95% CI, 1.62–3.65), and > 5 events (AOR, 3.11; 95% CI, 1.86–4.95).
Conclusions. Among HIV-seropositive IDUs receiving ART, an increasing burden of incarceration was associated with poorer adherence in a dose-dependent fashion. Our findings support improved adherence support for HIV-seropositive IDUs experiencing incarceration.
To model the effect of adherence and duration of viral suppression on the risk of viral rebound.
Viral rebound was defined as the first of at least 2 consecutive viral loads >400 copies/mL following initial viral suppression. The main exposures were adherence, presence of ARV class resistance before rebound or censoring date, and the percentage of follow-up time with viral suppression.
A total of 274 (N=1305; 21%) individuals experienced viral rebound. Median time of suppression before rebound was 2 years. Viral rebound was less likely to occur among those with longer duration of continuous viral suppression (odds ratio 0.37; 95% confidence interval [CI] 0.32-0.42). Among individuals with moderate levels of adherence (80%-<95%), the probability of virologic failure was 0.85 after being suppressed for 12 months and it was 0.08 after 72 months being suppressed (p-value <0.01). Individuals with drug resistance were at a higher risk of viral rebound.
The risk of viral rebound decreased with longer duration of viral suppression within each of adherence strata studied. While perfect adherence remains an important goal of therapy to prevent disease progression, individuals with long-term viral suppression may be able to miss more doses without experiencing viral rebound.
Adherence; HAART; virologic failure; viral rebound; resistance; long-term suppression
Because men in Africa are less likely to access HIV/AIDS care than women, we aimed to determine if men have differing outcomes from women across a nationally representative sample of adult patients receiving combination antiretroviral therapy in Uganda.
We estimated survival distributions for adult male and female patients using Kaplan-Meier, and constructed multivariable regressions to model associations of baseline variables with mortality. We assessed person-years of life lost up to age 55 by sex. To minimize the impact of patient attrition, we assumed a weighted 30% mortality rate among those lost to follow up.
We included data from 22,315 adults receiving antiretroviral therapy. At baseline, men tended to be older, had lower CD4 baseline values, more advanced disease, had pulmonary tuberculosis and had received less treatment follow up (all at p < 0.001). Loss to follow up differed between men and women (7.5 versus 5.9%, p < 0.001). Over the period of study, men had a significantly increased risk of death compared with female patients (adjusted hazard ratio 1.43, 95% CI 1.31-1.57, p < 0.001). The crude mortality rate for males differed importantly from females (43.9, 95% CI 40.7-47.0/1000 person-years versus 26.9, 95% CI 25.4-28.5/1000 person years, p < 0.001). The probability of survival was 91.2% among males and 94.1% among females at 12 months. Person-years of life lost was lower for females than males (689.7 versus 995.9 per 1000 person-years, respectively).
In order to maximize the benefits of antiretroviral therapy, treatment programmes need to be gender sensitive to the specific needs of both women and men. Particular efforts are needed to enroll men earlier into care.
Few studies have examined the link between health system strength and important public health outcomes across nations. We examined the association between health system indicators and mortality rates.
We used mixed effects linear regression models to investigate the strength of association between outcome and explanatory variables, while accounting for geographic clustering of countries. We modelled infant mortality rate (IMR), child mortality rate (CMR), and maternal mortality rate (MMR) using 13 explanatory variables as outlined by the World Health Organization.
Significant protective health system determinants related to IMR included higher physician density (adjusted rate ratio [aRR] 0.81; 95% Confidence Interval [CI] 0.71-0.91), higher sustainable access to water and sanitation (aRR 0.85; 95% CI 0.78-0.93), and having a less corrupt government (aRR 0.57; 95% CI 0.40-0.80). Out-of-pocket expenditures on health (aRR 1.29; 95% CI 1.03-1.62) were a risk factor. The same four variables were significantly related to CMR after controlling for other variables. Protective determinants of MMR included access to water and sanitation (aRR 0.88; 95% CI 0.82-0.94), having a less corrupt government (aRR 0.49; 95%; CI 0.36-0.66), and higher total expenditures on health per capita (aRR 0.84; 95% CI 0.77-0.92). Higher fertility rates (aRR 2.85; 95% CI: 2.02-4.00) were found to be a significant risk factor for MMR.
Several key measures of a health system predict mortality in infants, children, and maternal mortality rates at the national level. Improving access to water and sanitation and reducing corruption within the health sector should become priorities.