Thomas P. Giordano

Retention in Care: A Challenge to Survival with HIV Infection

BACKGROUND Patients with human immunodeficiency virus (HIV) infection need lifelong medical care, but many do not remain in care. The effect of poor retention in care on survival is not known, and we sought to quantify that relationship. METHODS We conducted a retrospective cohort study involving persons newly identified as having HIV infection during 1997-1998 at any United States Department of Veterans Affairs hospital or clinic who started antiretroviral therapy after 1 January 1997. To be included in the study, patients had to have seen a clinician at least once after receiving their first antiretroviral prescription and to have survived for at least 1 year. Patients were divided into 4 groups on the basis of the number of quarters in that year during which they had at least 1 HIV primary care visit. Survival was measured through 2002. Because data were available for only a small number of women, female patients were excluded from the study. RESULTS A total of 2619 men were followed up for a mean of >4 years each. The median baseline CD4(+) cell count and median log(10) plasma HIV concentration were 228x10(6) cells/L and 4.58 copies/mL, respectively. Thirty-six percent of the patients had visits in <4 quarters, and 16% died during follow-up. In Cox multivariate regression analysis, compared with persons with visits in all 4 quarters during the first year, the adjusted hazard ratio of death was 1.42 (95% confidence interval, 1.11-1.83; P<.01), 1.67 (95% confidence interval, 1.24-2.25; P<.001), and 1.95 (95% confidence interval, 1.37-2.78; P<.001) for persons with visits in 3 quarters, 2 quarters, and 1 quarter, respectively. CONCLUSIONS Even in a system with few financial barriers to care, a substantial portion of HIV-infected patients have poor retention in care. Poor retention in care predicts poorer survival with HIV infection. Retaining persons in care may improve survival, and optimal methods to retain patients need to be defined.

Screening HIV-Infected Individuals for Anal Cancer Precursor Lesions: A Systematic Review

Individuals with human immunodeficiency virus (HIV) infection are at increased risk for human papillomavirus-related squamous cell cancer of the anus. Screening HIV-infected patients for squamous cell cancer of the anus and human papillomavirus-related anal dysplasia may prevent excess morbidity and mortality. We have conducted a systematic review of the indirect evidence in the literature regarding the utility of anal Papanicolau (Pap) smear screening of HIV-infected individuals in the highly active antiretroviral therapy era. Although there are no published studies evaluating the efficacy of anal Pap smear screening for preventing squamous cell cancer of the anus or anal intraepithelial neoplasia, we reviewed data regarding the burden of disease, anal Pap smear sensitivity and specificity, the prevalence of anal dysplasia, and 1 cost effectiveness study. The available evidence demonstrates that HIV-infected individuals have an increased risk for squamous cell cancer of the anus and anal intraepithelial neoplasia. This review identifies important areas for further study before routine anal Pap smear screening can be recommended.

Measuring Adherence to Antiretroviral Therapy in a Diverse Population Using a Visual Analogue Scale

Abstract Purpose: To examine the performance of an instrument to assess adherence based on a visual analogue scale, compared to an instrument based on 3-day recall, using unannounced pill counts in the place of residence as the gold standard. Method: We prospectively assessed adherence to antiretroviral therapy in 84 marginally housed indigent HIV-infected patients who were receiving stable antiretroviral therapy in San Francisco, California, with three adherence assessments over no more than 4 months. Results: Mean adherence using the visual analogue scale, 3-day recall, and unannounced pill count methods were 82.5%, 84.2%, and 75.9%, respectively. The correlation between visual analogue scale and unannounced pill count was high (r = 0.76) and was not statistically different from that between 3-day recall and unannounced pill count (r = 0.71; p = .52). Both methods were also similarly inversely correlated with HIV viral load (r = -0.49 and -0.34, respectively; p = .22 for the difference in the correlations). The visual analogue scale correlation with unannounced pill count was stable over time and remained high in all subpopulations examined. Conclusion: A visual analogue scale to assess adherence was performed as well as a more complicated 3-day recall instrument in this diverse population. Given its simplicity, the visual analogue scale adherence instrument will be useful in research and may be useful in routine patient care.

Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population-based study of U.S. veterans†

Hepatitis C virus (HCV) may increase the risk of hepatopancreaticobiliary tumors other than hepatocellular carcinoma (HCC). Previous case control studies indicated a possible association between HCV and intrahepatic cholangiocarcinoma (ICC). Little is known about the association between HCV and extrahepatic cholangiocarcinoma (ECC) or pancreatic cancer. We conducted a cohort study including 146,394 HCV‐infected and 572,293 HCV‐uninfected patients who received care at Veterans Affairs health care facilities. Patients with two visits between 1996 and 2004 with HCV infection were included, as were up to four matched HCV‐uninfected subjects for each HCV‐infected subject. Risks of ICC, ECC, pancreatic cancer, and HCC were assessed using proportional hazards regression. In the 1.37 million person‐years of follow‐up, which began 6 months after the baseline visit, there were 75 cases of ECC, 37 cases of ICC, 617 cases of pancreatic cancer, and 1679 cases of HCC. As expected, the risk of HCC associated with HCV was very high (hazard ratio [HR], 15.09; 95% confidence interval [95% CI], 13.44, 16.94). Risk for ICC was elevated with HCV infection 2.55; 1.31, 4.95), but risk for ECC was not significantly increased (1.50; 0.60, 1.85). Adjustments for cirrhosis, diabetes, inflammatory bowel disease, hepatitis B, alcoholism, and alcoholic liver disease did not reduce the risk for ICC below twofold. The risk of pancreatic cancer was slightly elevated (1.23; 1.02, 1.49), but was attenuated after adjusting for alcohol use, pancreatitis, and other variables. Conclusions: Findings indicated that HCV infection conferred a more than twofold elevated risk of ICC. Absence of an association with ECC was consistent in adjusted and unadjusted models. A significant association with pancreatic cancer was erased by alcohol use and other variables. (HEPATOLOGY > 2009;49:116‐123.)

Lower Pill Burden and Once-Daily Antiretroviral Treatment Regimens for HIV Infection: A Meta-Analysis of Randomized Controlled Trials

Once-daily compared with twice-daily antiretroviral therapy regimens increased adherence; however, the difference was modest and not associated with a difference in virological suppression. In addition, higher pill burden was associated with lower rates of virological suppression, whether once- or twice-daily regimens.

The validity of viral hepatitis and chronic liver disease diagnoses in Veterans Affairs administrative databases

Background  The validity of International Classification of Diseases‐9 codes for liver disease has not been determined.

Measuring Retention in HIV Care: The Elusive Gold Standard

Background:Measuring retention in HIV primary care is complex, as care includes multiple visits scheduled at varying intervals over time. We evaluated 6 commonly used retention measures in predicting viral load (VL) suppression and the correlation among measures. Methods:Clinic-wide patient-level data from 6 academic HIV clinics were used for 12 months preceding implementation of the Centers for Disease Control and Prevention/Health Resources and Services Administration (CDC/HRSA) retention in care intervention. Six retention measures were calculated for each patient based on scheduled primary HIV provider visits: count and dichotomous missed visits, visit adherence, 6-month gap, 4-month visit constancy, and the HRSA HIV/AIDS Bureau (HRSA HAB) retention measure. Spearman correlation coefficients and separate unadjusted logistic regression models compared retention measures with one another and with 12-month VL suppression, respectively. The discriminatory capacity of each measure was assessed with the c-statistic. Results:Among 10,053 patients, 8235 (82%) had 12-month VL measures, with 6304 (77%) achieving suppression (VL <400 copies/mL). All 6 retention measures were significantly associated (P < 0.0001) with VL suppression (odds ratio; 95% CI, c-statistic): missed visit count (0.73; 0.71 to 0.75, 0.67), missed visit dichotomous (3.2; 2.8 to 3.6, 0.62), visit adherence (3.9; 3.5 to 4.3,0.69), gap (3.0; 2.6 to 3.3, 0.61), visit constancy (2.8; 2.5 to 3.0, 0.63), and HRSA HAB (3.8; 3.3 to 4.4, 0.59). Measures incorporating “no-show” visits were highly correlated (Spearman coefficient = 0.83–0.85), as were measures based solely on kept visits (Spearman coefficient = 0.72–0.77). Correlation coefficients were lower across these 2 groups of measures (range = 0.16–0.57). Conclusions:Six retention measures displayed a wide range of correlation with one another, yet each measure had significant association and modest discrimination for VL suppression. These data suggest there is no clear gold standard and that selection of a retention measure may be tailored to context.

Patients referred to an urban HIV clinic frequently fail to establish care: factors predicting failure

Abstract To measure the success with which patients newly entering outpatient care establish regular care, and assess whether race/ethnicity was a predictive factor, we conducted a medical record review of new patients seen 20 April 1998 to 31 December 1998 at The Thomas Street Clinic, a county clinic for uninsured persons. Patients were considered ‘not established’ if they never saw a physician in the 6 months after intake (the ‘initial period’), ‘poorly established’ if seen but a > 6-month gap in care began in the initial period, and ‘established’ if there were no such gaps. Of 404 patients, 11% were ‘not established’, 37% ‘poorly established’, and 53% ‘established’. Injection drug use as HIV risk factor (IDU), admitted current alcohol and drug use, age < 35 years, and CD4 count > / = 200 cells/mm3 were most common in the ‘not established’ group and least common in the ‘established’ group. In multivariate ordinal logistic regression, difficulty establishing care was associated with IDU, admitted current alcohol use, and admitted former drug use. Age > 35 years was protective. Half the indigent patients entering care in this single-site study fail to establish regular care. Substance use and younger age are predictors of failure to establish care.

Racial disparities in HIV virologic failure: Do missed visits matter?

Background:Racial/ethnic health care disparities are well described in people living with HIV/AIDS, although the processes underlying observed disparities are not well elucidated. Methods:A retrospective analysis nested in the University of Alabama at Birmingham 1917 Clinic Cohort observational HIV study evaluated patients between August 2004 and January 2007. Factors associated with appointment nonadherence, a proportion of missed outpatient visits, were evaluated. Next, the role of appointment nonadherence in explaining the relationship between African American race and virologic failure (plasma HIV RNA >50 copies/mL) was examined using a staged multivariable modeling approach. Results:Among 1221 participants, a broad distribution of appointment nonadherence was observed, with 40% of patients missing at least 1 in every 4 scheduled visits. The adjusted odds of appointment nonadherence were 1.85 times higher in African American patients compared with whites [95% confidence interval (CI) = 1.61 to 2.14]. Appointment nonadherence was associated with virologic failure (odds ratio = 1.78, 95% CI = 1.48 to 2.13) and partially mediated the relationship between African American race and virologic failure. African Americans had 1.56 times the adjusted odds of virologic failure (95% CI = 1.19 to 2.05), which declined to 1.30 (95% CI = 0.98 to 1.72) when controlling for appointment nonadherence, a hypothesized mediator. Conclusions:Appointment nonadherence was more common in African American patients, associated with virologic failure, and seemed to explain part of observed racial disparities in virologic failure.

The effect of HIV coinfection on the risk of cirrhosis and hepatocellular carcinoma in U.S. veterans with hepatitis C.

OBJECTIVES:This study was conducted to determine whether HIV coinfection increases the risk of cirrhosis in HCV-infected patients in the HAART and pre-HAART eras. Further, the risk of hepatocellular carcinoma was also examined.METHODS:This retrospective cohort study was conducted among HCV-infected veterans who were seen at one of the 172 Veterans Health Administration hospitals between October 1, 1991 and September 30, 2000. Patients with prerecorded advanced liver disease were excluded. Incidence rates, cumulative incidence, and Cox proportional hazard ratios were calculated.RESULTS:There were 26,641 patients with HCV-only and 4,761 patients with HCV–HIV coinfection. The unadjusted incidence rate of cirrhosis was lower in patients with coinfection than HCV-only (p < 0.01). After controlling for demographics and confounders (including alcoholism and chronic hepatitis B), coinfection was not significantly associated with cirrhosis. However, there was an increased risk of cirrhosis in patients with coinfection compared to HCV-only during the pre-HAART era (before October 1, 1996) (hazard ratio = 1.48, 1.06–2.07, p= 0.02), but not among patients who entered the cohort during the HAART era. The unadjusted incidence rate of hepatocellular carcinoma in patients with coinfection and HCV-only was 1.3 and 2/1,000 person-years, respectively (p= 0.04). In the multivariate model, coinfection was not associated with hepatocellular carcinoma (hazard ratio = 0.84, p= 0.40).CONCLUSIONS:Coinfection was a significant risk factor for cirrhosis only during the pre-HAART era and was not associated with hepatocellular carcinoma, irrespective of time period.