Impact of a nurse vaccination program on hepatitis B immunity in a Swiss HIV clinic

We evaluated the impact of a nurse program for hepatitis B virus vaccination in a center from the Swiss HIV Cohort Study. Immunity (anti-HBs >10 IU/mL) increased from 32% to 76% in the intervention center (n = 238) where vaccine management was endorsed by nurses, but only from 33% to 39% in control centers (n = 2712, P < 0.001) where management remained in charge of physicians. Immunity against HBV in the HIV population is insufficient in Switzerland. Specific nurse vaccination program may efficiently improve health care.

Immunologic response to antiretroviral therapy in hepatitis C virus-coinfected adults in a population-based HIV/AIDS treatment program

BACKGROUND: We sought to characterize the impact that hepatitis C virus (HCV) infection has on CD4 cells during the first 48 weeks of antiretroviral therapy (ART) in previously ART-naive human immunodeficiency virus (HIV)-infected patients. METHODS: The HIV/AIDS Drug Treatment Programme at the British Columbia Centre for Excellence in HIV/AIDS distributes all ART in this Canadian province. Eligible individuals were those whose first-ever ART included 2 nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor and who had a documented positive result for HCV antibody testing. Outcomes were binary events (time to an increase of > or = 75 CD4 cells/mm3 or an increase of > or = 10% in the percentage of CD4 cells in the total T cell population [CD4 cell fraction]) and continuous repeated measures. Statistical analyses used parametric and nonparametric methods, including multivariate mixed-effects linear regression analysis and Cox proportional hazards analysis. RESULTS: Of 1186 eligible patients, 606 (51%) were positive and 580 (49%) were negative for HCV antibodies. HCV antibody-positive patients were slower to have an absolute (P<.001) and a fraction (P = .02) CD4 cell event. In adjusted Cox proportional hazards analysis (controlling for age, sex, baseline absolute CD4 cell count, baseline pVL, type of ART initiated, AIDS diagnosis at baseline, adherence to ART regimen, and number of CD4 cell measurements), HCV antibody-positive patients were less likely to have an absolute CD4 cell event (adjusted hazard ratio [AHR], 0.84 [95% confidence interval [CI], 0.72-0.98]) and somewhat less likely to have a CD4 cell fraction event (AHR, 0.89 [95% CI, 0.70-1.14]) than HCV antibody-negative patients. In multivariate mixed-effects linear regression analysis, HCV antibody-negative patients had increases of an average of 75 cells in the absolute CD4 cell count and 4.4% in the CD4 cell fraction, compared with 20 cells and 1.1% in HCV antibody-positive patients, during the first 48 weeks of ART, after adjustment for time-updated pVL, number of CD4 cell measurements, and other factors. CONCLUSION: HCV antibody-positive HIV-infected patients may have an altered immunologic response to ART.

Low Risk of Death, but Substantial Program Attrition, in Pediatric HIV Treatment Cohorts in Sub-Saharan Africa

BACKGROUND: To date, an estimated 10% of children eligible for antiretroviral treatment (ART) receive it, and the frequency of retention in programs is unknown. We evaluated the 2-year risks of death and loss to follow-up (LTFU) of children after ART initiation in a multicenter study in sub-Saharan Africa. METHODS: Pooled analysis of routine individual data from 16 participating clinics produced overall Kaplan-Meier estimates of the probabilities of death or LTFU after ART initiation. Risk factors analysis used Weibull regression, accounting for between-cohort heterogeneity. RESULTS: The median age of 2405 children at ART initiation was 4.9 years (12%, younger than 12 months), 52% were male, 70% had severe immunodeficiency, and 59% started ART with a nonnucleoside reverse transcriptase inhibitor. The 2-year risk of death after ART initiation was 6.9% (95% confidence interval [CI]: 5.9 to 8.1), independently associated with baseline severe anemia (adjusted hazard ratio [aHR]: 4.10 [CI: 2.36 to 7.13]), immunodeficiency (adjusted aHR: 2.95 [CI: 1.49 to 5.82]), and severe clinical status (adjusted aHR: 3.64 [CI: 1.95 to 6.81]); the 2-year risk of LTFU was 10.3% (CI: 8.9 to 11.9), higher in children with severe clinical status. CONCLUSIONS: Once on treatment, the 2-year risk of death is low but the LTFU risk is substantial. ART is still mainly initiated at advanced disease stage in African children, reinforcing the need for early HIV diagnosis, early initiation of ART, and procedures to increase program retention.

Choice of Initial Combination Antiretroviral Therapy in Individuals With HIV Infection: Determinants and Outcomes

BACKGROUND Current guidelines give recommendations for preferred combination antiretroviral therapy (cART). We investigated factors influencing the choice of initial cART in clinical practice and its outcome. METHODS We analyzed treatment-naive adults with human immunodeficiency virus (HIV) infection participating in the Swiss HIV Cohort Study and starting cART from January 1, 2005, through December 31, 2009. The primary end point was the choice of the initial antiretroviral regimen. Secondary end points were virologic suppression, the increase in CD4 cell counts from baseline, and treatment modification within 12 months after starting treatment. RESULTS A total of 1957 patients were analyzed. Tenofovir-emtricitabine (TDF-FTC)-efavirenz was the most frequently prescribed cART (29.9%), followed by TDF-FTC-lopinavir/r (16.9%), TDF-FTC-atazanavir/r (12.9%), zidovudine-lamivudine (ZDV-3TC)-lopinavir/r (12.8%), and abacavir/lamivudine (ABC-3TC)-efavirenz (5.7%). Differences in prescription were noted among different Swiss HIV Cohort Study sites (P < .001). In multivariate analysis, compared with TDF-FTC-efavirenz, starting TDF-FTC-lopinavir/r was associated with prior AIDS (relative risk ratio, 2.78; 95% CI, 1.78-4.35), HIV-RNA greater than 100 000 copies/mL (1.53; 1.07-2.18), and CD4 greater than 350 cells/μL (1.67; 1.04-2.70); TDF-FTC-atazanavir/r with a depressive disorder (1.77; 1.04-3.01), HIV-RNA greater than 100 000 copies/mL (1.54; 1.05-2.25), and an opiate substitution program (2.76; 1.09-7.00); and ZDV-3TC-lopinavir/r with female sex (3.89; 2.39-6.31) and CD4 cell counts greater than 350 cells/μL (4.50; 2.58-7.86). At 12 months, 1715 patients (87.6%) achieved viral load less than 50 copies/mL and CD4 cell counts increased by a median (interquartile range) of 173 (89-269) cells/μL. Virologic suppression was more likely with TDF-FTC-efavirenz, and CD4 increase was higher with ZDV-3TC-lopinavir/r. No differences in outcome were observed among Swiss HIV Cohort Study sites. CONCLUSIONS Large differences in prescription but not in outcome were observed among study sites. A trend toward individualized cART was noted suggesting that initial cART is significantly influenced by physician's preference and patient characteristics. Our study highlights the need for evidence-based data for determining the best initial regimen for different HIV-infected persons.

Prevalence of risk factors for cardiovascular disease in HIV-infected patients over time: the Swiss HIV Cohort Study

OBJECTIVE: Metabolic changes caused by antiretroviral therapy (ART) may increase the risk of coronary heart disease (CHD). We evaluated changes in the prevalence of cardiovascular risk factors (CVRFs) and 10-year risk of CHD in a large cohort of HIV-infected individuals. METHODS: All individuals from the Swiss HIV Cohort Study (SHCS) who completed at least one CVRF questionnaire and for whom laboratory data were available for the period February 2000 to February 2006 were included in the analysis. The presence of a risk factor was determined using cut-offs based on the guidelines of the National Cholesterol Education Program (NCEP ATP III), the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), the American Diabetes Association, and the Swiss Society for Cardiology. RESULTS: Overall, 8,033 individuals completed at least one CVRF questionnaire. The most common CVRFs in the first completed questionnaire were smoking (57.0%), low high-density lipoprotein (HDL) cholesterol (37.2%), high triglycerides (35.7%), and high blood pressure (26.1%). In total, 2.7 and 13.8% of patients were categorized as being at high (>20%) and moderate (10-20%) 10-year risk for CHD, respectively. Over 6 years the percentage of smokers decreased from 61.4 to 47.6% and the percentage of individuals with total cholesterol >6.2 mmol/L decreased from 21.1 to 12.3%. The prevalence of CVRFs and CHD risk was higher in patients currently on ART than in either pretreated or ART-naive patients. CONCLUSION: During the 6-year observation period, the prevalence of CVRFs remains high in the SHCS. Time trends indicate a decrease in the percentage of smokers and individuals with high cholesterol.

Hepatitis C coinfection is independently associated with decreased adherence to antiretroviral therapy in a population-based HIV cohort

OBJECTIVE: To characterize the impact of hepatitis C (HCV) serostatus on adherence to antiretroviral treatment (ART) among HIV-infected adults initiating ART. METHODS: The British Columbia HIV/AIDS Drug Treatment Program distributes, at no cost, all ART in this Canadian province. Eligible individuals used triple combination ART as their first HIV therapy and had documented HCV serology. Statistical analyses used parametric and non-parametric methods, including multivariate logistic regression. The primary outcome was > or = 95% adherence, defined as receiving > or = 95% of prescription refills during the first year of antiretroviral therapy. RESULTS: There were 1186 patients eligible for analysis, including 606 (51%) positive for HCV antibody and 580 (49%) who were negative. In adjusted analyses, adherence was independently associated with HCV seropositivity [adjusted odds ratio (AOR), 0.48; 95% confidence interval (CI), 0.23-0.97; P = 0.003], higher plasma albumin levels (AOR, 1.07; 95% CI, 1.01-1.12; P = 0.002) and male gender (AOR, 2.53; 95% CI, 1.04-6.15; P = 0.017), but not with injection drug use (IDU), age or other markers of liver injury. There was no evidence of an interaction between HCV and liver injury in adjusted analyses; comparing different strata of HCV and IDU confirmed that HCV was associated with poor adherence independent of IDU. CONCLUSIONS: HCV-coinfected individuals and those with lower albumin are less likely to be adherent to their ART.

Are They Really Lost? "True" Status and Reasons for Treatment Discontinuation among HIV Infected Patients on Antiretroviral Therapy Considered Lost to Follow Up in Urban Malawi

INTRODUCTION Patients who are lost to follow-up (LTFU) while on antiretroviral therapy (ART) pose challenges to the long-term success of ART programs. We describe the extent to which patients considered LTFU are misclassified as true disengagement from care when they are still alive on ART and explain reasons for ART discontinuation using our active tracing program to further improve ART retention programs and policies. METHODS We identified adult ART patients who missed clinic appointment by more than 3 weeks between January 2006 and December 2010, assuming that such patients would miss their doses of antiretroviral drugs. Patients considered LTFU who consented during ART registration were traced by phone or home visits; true ART status after tracing was documented. Reasons for ART discontinuation were also recorded for those who stopped ART. RESULTS Of the 4,560 suspected LTFU cases, 1,384 (30%) could not be traced. Of the 3,176 successfully traced patients, 952 (30%) were dead and 2,224 (70%) were alive, of which 2,183 (99.5%) started ART according to phone-based self-reports or physical verification during in-person interviews. Of those who started ART, 957 (44%) stopped ART and 1,226 (56%) reported still taking ART at the time of interview by sourcing drugs from another clinic, using alternative ART sources or making brief ART interruptions. Among 940 cases with reasons for ART discontinuations, failure to remember (17%), too weak/sick (12%), travel (46%), and lack of transport to the clinic (16%) were frequently cited; reasons differed by gender. CONCLUSION The LTFU category comprises sizeable proportions of patients still taking ART that may potentially bias retention estimates and misdirect resources at the clinic and national levels if not properly accounted for. Clinics should consider further decentralization efforts, increasing drug allocations for frequent travels, and improving communication on patient transfers between clinics to increase retention and adherence.

A survey of paediatric HIV programmatic and clinical management practices in Asia and sub-Saharan Africa--the International epidemiologic Databases to Evaluate AIDS (IeDEA)

INTRODUCTION There are limited data on paediatric HIV care and treatment programmes in low-resource settings. METHODS A standardized survey was completed by International epidemiologic Databases to Evaluate AIDS paediatric cohort sites in the regions of Asia-Pacific (AP), Central Africa (CA), East Africa (EA), Southern Africa (SA) and West Africa (WA) to understand operational resource availability and paediatric management practices. Data were collected through January 2010 using a secure, web-based software program (REDCap). RESULTS A total of 64,552 children were under care at 63 clinics (AP, N=10; CA, N=4; EA, N=29; SA, N=10; WA, N=10). Most were in urban settings (N=41, 65%) and received funding from governments (N=51, 81%), PEPFAR (N=34, 54%), and/or the Global Fund (N=15, 24%). The majority were combined adult-paediatric clinics (N=36, 57%). Prevention of mother-to-child transmission was integrated at 35 (56%) sites; 89% (N=56) had access to DNA PCR for infant diagnosis. African (N=40/53) but not Asian sites recommended exclusive breastfeeding up until 4-6 months. Regular laboratory monitoring included CD4 (N=60, 95%), and viral load (N=24, 38%). Although 42 (67%) sites had the ability to conduct acid-fast bacilli (AFB) smears, 23 (37%) sites could conduct AFB cultures and 18 (29%) sites could conduct tuberculosis drug susceptibility testing. Loss to follow-up was defined as >3 months of lost contact for 25 (40%) sites, >6 months for 27 sites (43%) and >12 months for 6 sites (10%). Telephone calls (N=52, 83%) and outreach worker home visits to trace children lost to follow-up (N=45, 71%) were common. CONCLUSIONS In general, there was a high level of patient and laboratory monitoring within this multiregional paediatric cohort consortium that will facilitate detailed observational research studies. Practices will continue to be monitored as the WHO/UNAIDS Treatment 2.0 framework is implemented.

Prognosis of Children with HIV-1 Infection Starting Antiretroviral Therapy in Southern Africa: A Collaborative Analysis of Treatment Programs

BACKGROUND: Prognostic models for children starting antiretroviral therapy (ART) in Africa are lacking. We developed models to estimate the probability of death during the first year receiving ART in Southern Africa. METHODS: We analyzed data from children ≤10 years old who started ART in Malawi, South Africa, Zambia or Zimbabwe from 2004-2010. Children lost to follow-up or transferred were excluded. The primary outcome was all-cause mortality in the first year of ART. We used Weibull survival models to construct two prognostic models: one with CD4%, age, WHO clinical stage, weight-for-age z-score (WAZ) and anemia and one without CD4%, because it is not routinely measured in many programs. We used multiple imputation to account for missing data. RESULTS: Among 12655 children, 877 (6.9%) died in the first year of ART. 1780 children were lost to follow-up/transferred and excluded from main analyses; 10875 children were included. With the CD4% model probability of death at 1 year ranged from 1.8% (95% CI: 1.5-2.3) in children 5-10 years with CD4% ≥10%, WHO stage I/II, WAZ ≥-2 and without severe anemia to 46.3% (95% CI: 38.2-55.2) in children <1 year with CD4% <5%, stage III/IV, WAZ< -3 and severe anemia. The corresponding range for the model without CD4% was 2.2% (95% CI: 1.8-2.7) to 33.4% (95% CI: 28.2-39.3). Agreement between predicted and observed mortality was good (C-statistics=0.753 and 0.745 for models with and without CD4% respectively). CONCLUSION: These models may be useful to counsel children/caregivers, for program planning and to assess program outcomes after allowing for differences in patient disease severity characteristics.

Retention in care under universal antiretroviral therapy for HIV-infected pregnant and breastfeeding women ('Option B+') in Malawi

OBJECTIVE To explore the levels and determinants of loss to follow-up (LTF) under universal lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') in Malawi. DESIGN, SETTING, AND PARTICIPANTS We examined retention in care, from the date of ART initiation up to 6 months, for women in the Option B+ program. We analysed nationwide facility-level data on women who started ART at 540 facilities (n = 21 939), as well as individual-level data on patients who started ART at 19 large facilities (n = 11 534). RESULTS Of the women who started ART under Option B+ (n = 21 939), 17% appeared to be lost to follow-up 6 months after ART initiation. Most losses occurred in the first 3 months of therapy. Option B+ patients who started therapy during pregnancy were five times more likely than women who started ART in WHO stage 3/4 or with a CD4 cell count 350 cells/μl or less, to never return after their initial clinic visit [odds ratio (OR) 5.0, 95% confidence interval (CI) 4.2-6.1]. Option B+ patients who started therapy while breastfeeding were twice as likely to miss their first follow-up visit (OR 2.2, 95% CI 1.8-2.8). LTF was highest in pregnant Option B+ patients who began ART at large clinics on the day they were diagnosed with HIV. LTF varied considerably between facilities, ranging from 0 to 58%. CONCLUSION Decreasing LTF will improve the effectiveness of the Option B+ approach. Tailored interventions, like community or family-based models of care could improve its effectiveness.

Kaposi's Sarcoma in HIV-infected patients in South Africa: Multicohort study in the antiretroviral therapy era

The incidence of Kaposi's Sarcoma (KS) is high in South Africa but the impact of antiretroviral therapy (ART) is not well defined. We examined incidence and survival of KS in HIV-infected patients enrolled in South African ART programs. We analyzed data of three ART programs: Khayelitsha township and Tygerberg Hospital programs in Cape Town and Themba Lethu program in Johannesburg. We included patients aged >16 years. ART was defined as a regimen of at least three drugs. We estimated incidence rates of KS for patients on ART and not on ART. We calculated Cox models adjusted for age, sex and time-updated CD4 cell counts and HIV-1 RNA. A total of 18,254 patients (median age 34.5 years, 64% female, median CD4 cell count at enrolment 105 cells/μL) were included. During 37,488 person-years follow-up 162 patients developed KS. The incidence was 1,682/100,000 person-years (95% confidence interval [CI] 1,406-2,011) among patients not receiving ART and 138/100,000 person-years (95% CI 102-187) among patients on ART. The adjusted hazard ratio comparing time on ART with time not on ART was 0.19 (95% CI 0.13-0.28). Low CD4 cell counts (time-updated) and male sex were also associated with KS. Estimated survival of KS patients at one year was 72.2% (95% CI 64.9-80.2) and higher in men than in women. The incidence of KS is substantially lower on ART than not on ART. Timely initiation of ART is essential to prevent KS and KS-associated morbidity and mortality in South Africa and other regions in Africa with a high burden of HIV.

Detection and management of drug-resistant tuberculosis in HIV-infected patients in lower-income countries.

SETTING Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons. OBJECTIVE To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries. DESIGN We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n = 14), East Africa (n = 8), West Africa (n = 7), Central Africa (n = 5), Latin America (n = 7) and the Asia-Pacific (n = 6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs. RESULTS Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages. CONCLUSIONS Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.