The implementation of the DHHS guidelines for the use of antiretroviral agents in HIV-infected adults: a pilot study

The objective of this study was to assess whether United States DHHS guidelines for treatment with antiretroviral therapies are being implemented by health care providers when discussing treatment options with newly diagnosed HIV patients. Health care providers were observed interacting with HIV patients while making decisions about treatment. Observers assessed whether providers and patients discussed the five benefits and six risks of initiating antiretroviral therapy, as recommended in the DHHS Guidelines. Preliminary results indicate that the DHHS Guidelines are not being implemented in the way they were intended. The risks and benefits of antiretroviral therapy were infrequently discussed. No more than four of the 11 risk/benefit items were discussed with any patient, and four of the six risk items were never mentioned to any patient. Potential reasons why the guidelines are not being implemented are discussed.     

Incidence of and risk factors for bacteraemia in HIV-infected adults in the era of highly active antiretroviral therapy

Background

HIV‐infected patients have an increased risk for bacteraemia compared with HIV‐negative patients. Few data exist on the incidence of and risk factors for bacteraemia across time in the current era of highly active antiretroviral therapy (HAART).

Methods

We assessed the incidence of bacteraemia among patients followed between 2000 and 2008 at 10 HIV Research Network sites. This large multisite, multistate clinical cohort study collected demographic, clinical and therapeutic data longitudinally. International Statistical Classification of Diseases and Related Health Problems (ICD)‐9 codes were examined to identify all cases of in‐patient bacteraemia. Logistic regression analysis was used to assess risk factors for bacteraemia and trends over time in the odds of bacteraemia.

Results

A total of 39 318 patients were followed for 146 289 person‐years (PY). During the study period, there were 2025 episodes of bacteraemia (incidence 13.8 events/1000 PY). The most common bacteraemia diagnosis was ‘bacteraemia, not otherwise specified (NOS)’ (51%) followed by Staphylococcus aureus (16%) and Streptococcus species (6.5%). In multivariate analysis, the likelihood of bacteraemia was found to have increased in 2005–2008, compared with 2000. Other factors associated with higher odds of bacteraemia included a history of injection drug use (IDU), age ≥50 years, Black race and greater immunosuppression.

Conclusions

The likelihood of bacteraemia has risen slightly in recent years. Patients who are Black or have a history of IDU are at higher risk. Further research is needed to identify reasons for this increase and to evaluate programmes designed to reduce the bacteraemia risk.     

When to start highly active antiretroviral therapy in chronically HIV-infected patients: evidence from the ICONA study

OBJECTIVES: To compare the response to highly active antiretroviral therapy (HAART) in individuals starting HAART at different CD4 cell counts. DESIGN: The mean increase in CD4 cell count and rate of virological failure after commencing HAART were measured in antiretroviral-naive patients (1421) in a large, non-randomized multicentre, observational study in Italy (ICONA). Clinical endpoints were also evaluated in a subset of patients who started HAART with a very low CD4 cell count. RESULTS: After 96 weeks of therapy, the mean rise in CD4 cell count was 280, 281 and 186 x 10(6) cells/l in patients starting HAART with a CD4 cell count < 200, 201--350 and > 350 x 10(6) cells/l, respectively. Patients starting HAART with a CD4 cell count < 200 x 10(6) cells/l tended to have a higher risk of subsequent virological failure [relative hazard (RH), 1.15; 95% confidence interval (CI), 0.93--1.42] compared with patients starting with > 350 x 10(6) cells/l. There was no difference in risk between the 201--350 and the > 350 x 10(6) cells/l groups (RH, 1.0; 95% CI, 0.79--1.29). The incidence of new AIDS-defining diseases/death in patients who started HAART with a CD4 count < 50 was 0.03/person-year (95% CI, 0.10--0.33) during the time in which the patient's CD4 cell count had been raised to > 200 x 10(6) cells/l. CONCLUSIONS: There was no clear immunological or virological advantage in starting HAART at a CD4 cell count > 350 rather than at 200--350 x 10(6) cells/l. The increase in CD4 cells restored by HAART is meaningful in that they are associated with reduced risk of disease/death.     

Long-term kinetics of T cell production in HIV-infected subjects treated with highly active antiretroviral therapy

The long-term kinetics of T cell production following highly active antiretroviral therapy (HAART) were investigated in blood and lymph node in a group of HIV-infected subjects at early stage of established infection and prospectively studied for 72 wk. Before HAART, CD4 and CD8 T cell turnover was increased. However, the total number of proliferating CD4(+) T lymphocytes, i.e., CD4(+)Ki67(+) T lymphocytes, was not significantly different in HIV-infected (n = 73) and HIV-negative (n = 15) subjects, whereas proliferating CD8(+)Ki67(+) T lymphocytes were significantly higher in HIV-infected subjects. After HAART, the total body number of proliferating CD4(+)Ki67(+) T lymphocytes increased over time and was associated with an increase of both naive and memory CD4(+) T cells. The maximal increase (2-fold) was observed at week 36, whereas at week 72 the number of proliferating CD4(+) T cells dropped to baseline levels, i.e., before HAART. The kinetics of the fraction of proliferating CD4 and CD8 T cells were significantly correlated with the changes in the total body number of these T cell subsets. These results demonstrate a direct relationship between ex vivo measures of T cell production and quantitative changes in total body T lymphocyte populations. This study provides advances in the delineation of the kinetics of T cell production in HIV infection in the presence and/or in the absence of HAART.     

Durability and predictors of success of highly active antiretroviral therapy for ambulatory HIV-infected patients

OBJECTIVE: To evaluate the durability and correlates of the effectiveness of highly active antiretroviral therapy (HAART) in terms of AIDS-related mortality and morbidity, HIV viremia, and CD4 cell count. DESIGN AND SETTING: The HIV Outpatient Study (HOPS), a prospective observational cohort from eight clinics in the USA that has been running since 1994. PARTICIPANTS: Mortality and opportunistic infection (OI) rates were calculated for 1769 HOPS patients with CD4 cell count ever < 100 x 106/l. Data from 1022 HAART recipients with CD4 cell count ever < 500 x 106/l were analyzed. MAIN OUTCOME MEASURES: Mortality and AIDS-related OI rates. Treatment success was defined as a reduction in plasma HIV RNA copies/ml of 1.0 log10 or more, or to an undetectable level, with a stable or rising CD4 cell count. Durable success was a successful response lasting at least 12 consecutive months. RESULTS: HAART use remained high; mortality and OIs low. Patients received a mean of 1.8 HAART regimens. Median time on first HAART (n = 1022) was 11.8 months; second HAART (n = 424) 7.4 months; and third HAART (n = 213) 7.2 months. Treatment success was most likely for pre-HAART treatment naive patients; durably successful first HAART most often contained one protease inhibitor, particularly indinavir or nelfinavir (P = 0.006, adjusted for prior antiretroviral therapy). Durable success was most likely with first (49.0%) than with second (29.6%, P = 0.013) or third or more HAART regimens (14.9%, P < 0.0001). Time to success with first HAART was shorter for durable than non-durable responders (3.6 versus 5.3 months, respectively; unadjusted P = 0.002). CONCLUSIONS: Durable response to HAART was associated with being pre-HAART therapy naive, prompt response to HAART, and single protease inhibitor-based initial HAART (indinavir or nelfinavir). Sequential HAART regimens were of progressively shorter duration, demonstrated less viral suppression and CD4 cell count benefit, yet low morbidity and mortality rates were sustained.     

Discontinuation of maintenance therapy for cytomegalovirus retinitis in HIV-infected patients receiving highly active antiretroviral therapy

OBJECTIVE: To study the safety of discontinuing cytomegalovirus (CMV) maintenance therapy among patients with cured CMV retinitis receiving highly active antiretroviral therapy (HAART). METHODS: Patients with a history of CMV retinitis who were receiving anti-CMV maintenance therapy and who had a CD4 cell count > 75 x 10(6) cells/l and a plasma HIV RNA level < 30000 copies/ml while on HAART were included in a multicentre prospective study. Maintenance therapy for CMV retinitis was discontinued at enrolment and all the patients were monitored for 48 weeks by ophthalmological examinations and by determination of CMV markers, CD4 cell counts and plasma HIV RNA levels. T helper-1 anti-CMV responses were assessed in a subgroup of patients. The primary study endpoint was recurrence of CMV disease. RESULTS: At entry, the 48 assessable patients had been taking HAART for a median of 18 months. The median CD4 cell count was 239 x 10(6) cells/l and the median HIV RNA load was 213 copies/ml. Over the 48 weeks, 2 of the 48 patients had a recurrence of CMV disease. The cumulative probability of CMV retinitis relapse was 2.2% at week 48 (95% confidence interval, 0.4-11.3) and that of all forms of CMV disease 4.2%. CMV blood markers remained negative throughout follow-up. The proportion of patients with CMV-specific CD4 T cell reactivity was 46% at baseline and 64% at week 48. CONCLUSIONS: CMV retinitis maintenance therapy may be safely discontinued in patients with CD4 cell counts above 75 x 10(6) cells/l who have been taking HAART for at least 18 months.     

Randomized controlled trial of a personalized cellular phone reminder system to enhance adherence to antiretroviral therapy

Adherence to antiretroviral therapy (ART) represents one of the strongest predictors of progression to AIDS, yet it is difficult for most patients to sustain high levels of adherence. This study compares the efficacy of a personalized cell phone reminder system (ARemind) in enhancing adherence to ART versus a beeper. Twenty-three HIV-infected subjects on ART with self-reported adherence less than 85% were randomized to a cellular phone (CP) or beeper (BP). CP subjects received personalized text messages daily; in contrast, BP subjects received a reminder beep at the time of dosing. Interviews were scheduled at weeks 3 and 6. Adherence to ART was measured by self-report (SR, 7-day recall), pill count (PC, past 30 days at baseline, then past 3 weeks), Medication Event Monitoring System (MEMS; cumulatively at 3 and 6 weeks), and via a composite adherence score constructed by combining MEMS, pill count, and self report. A mixed effects model adjusting for baseline adherence was used to compare adherence rates between the intervention groups at 3 and 6 weeks. Nineteen subjects completed all visits, 10 men and 9 females. The mean age was 42.7 ± 6.5 years, 37% of subjects were Caucasian and 89% acquired HIV heterosexually. The average adherence to ART was 79% by SR and 65% by PC at baseline in both arms; over 6 weeks adherence increased and remained significantly higher in the ARemind group using multiple measures of adherence. A larger and longer prospective study is needed to confirm these findings and to better understand optimal reminder messages and user fatigue.     

Trends and predictors of quality of life among HIV-infected adults taking highly active antiretroviral therapy in rural Uganda

We examined trends and predictors of quality of life (QOL) over 12 months among a prospective cohort of 947 HIV-1-infected adults initiating highly active antiretroviral therapy (HAART) between May 2003 and May 2004 in rural Uganda. Participants provided clinical, demographic and psychosocial data at baseline and every three months thereafter. Outcome measures included physical and mental health summary scores based on the Medical Outcomes Study-HIV Health Survey (MOS-HIV). Generalised estimating equations were used to assess magnitude of change in summary scores and factors associated with QOL. Of 710 women and 237 men enrolled, the mean age was 38.7 years and mean baseline CD4 cell count was 124.1 cells/microL. At enrollment, physical and mental health summary scores were 39.2 and 40, respectively. By 12 months of HAART, scores increased by 11.2 points (p <0.001) and 7.4 points (p <0.001), respectively. For both scores, most gains were achieved by the third month of therapy. While several clinical, psychosocial and sociodemographic factors predicted QOL at HAART initiation, financial dependence on others was the only remaining predictor after controlling for time on HAART. Interventions to enhance the economic and employment opportunities of patients taking HAART in rural Africa may help maximise gains in QOL.     

The eldest of older adults living with HIV: response and adherence to highly active antiretroviral therapy

Objective

The study objective was to analyze the characteristics and the response to therapy in the eldest of the older adults living with human immunodeficiency virus.

Methods

The study included a cohort of patients with human immunodeficiency virus aged 55 years or more on initiating highly active antiretroviral therapy (HAART). Immunologic and virologic response, morbidity, and mortality were assessed. Patients were categorized as aged less than 65 years and 65 years or more.

Results

A total of 112 patients were included (82 patients aged < 65 years and 30 patients aged ≥ 65 years). There were no differences between the age groups in baseline characteristics, survival, and virologic response. There was a trend toward better adherence and a lower CD4+ cell increase after HAART in the older group.

Conclusion

A relationship was found between lower CD4+ cell increase after HAART and advanced age. We found the best adherence to treatment in the eldest of the older adults, and this has been shown to be the only protective independent factor related to virologic failure.     

Reconstitution of herpes simplex virus-specific T cell immunity in HIV-infected patients receiving highly active antiretroviral therapy

Production of herpes simplex virus (HSV)-specific interferon- gamma by peripheral-blood mononuclear cells (PBMCs) of HSV-seropositive healthy donors and human immunodeficiency virus-infected persons was determined by use of ELISPOT. The mean +/- SD number of spot-forming cells/10(6) PBMCs was 314 +/- 74 in 11 healthy donors, 360 +/- 69 in 3 long-term nonprogressors (LTNPs), 186 +/- 52 in 9 newly diagnosed patients, and 181 +/- 59 in 33 patients who were receiving highly active antiretroviral therapy (HAART) for a median period of 30 months (range, 1-109 months). In 9 patients monitored prospectively while receiving virologically and immunologically successful first-line HAART, the number of spot-forming cells increased by 5.6/month (95% confidence interval, 1.2-9.9 [P=.01]) and 21.3/100 CD4 cells/mm(3) gained (95% confidence interval, 13.8-28.7 [P<.0001]). Responses were correlated with LTNP status and CD4 cell count.     

Setting a minimum threshold CD4 count for initiation of highly active antiretroviral therapy in HIV-infected patients

The aim of our study was to determine a minimum threshold CD4 count for highly active antiretroviral therapy (HAART) initiation in HIV-infected patients. A schema using longitudinal data from a clinical cohort was designed. The presenting CD4 counts of asymptomatic HIV-infected patients in Hong Kong were evaluated in relation to their progression to AIDS within 1 year of diagnosis of HIV infection. A graph was generated to depict the changes in the percentage of cumulative AIDS diagnoses for every 10 cell/microL increase in presenting CD4 count. Of 181 patients, 24 had developed AIDS within 1 year of diagnosis of HIV infection. Setting the CD4 count threshold at 150 cells/microL gave a good balance between the number of preventable AIDS-defining events and the number of non-AIDS patients initiating HAART. No extra AIDS-defining events occurred when the CD4 count threshold was reduced from 200 to 150 cells/microL, despite the addition of 13 more patients. In multivariate Cox regression analysis, presenting CD4 count was a significant predictor for AIDS occurrence. The relative hazard for AIDS occurrence of patients with presenting CD4 counts 相似文献   

Discontinuation of secondary prophylaxis for opportunistic infections in HIV-infected patients receiving highly active antiretroviral therapy

BACKGROUND: Immune reconstitution following the introduction of highly active antiretroviral therapies (HAART) has lead to a remarkable reduction in the incidence of opportunistic infections (OI) in subjects with advanced HIV disease. Moreover, discontinuation of primary prophylaxis for some OI can be attempted without risk in patients experiencing a favourable response to treatment. However, data on the feasibility of discontinuing secondary prophylaxis are much more scarce, and restricted mainly to the withdrawal of maintenance treatment for cytomegalovirus (CMV) retinitis. PATIENTS AND METHODS: Retrospective review of the clinical outcome at 18 months in HIV-infected patients in whom discontinuation of secondary prophylaxis, for different OI, was recommended 3 months after the introduction of HAART, if both CD4 counts > 100 x 10(6) CD4 lymphocytes/l and plasma HIV-RNA < 500 copies/ml had been achieved. RESULTS: Fifty-three subjects were analysed. Secondary chemoprophylaxis was discontinued for the following OI: Pneumocystis carinii pneumonia (PCP) (n = 29), cerebral toxoplasmosis (n = 9), disseminated Mycobacterium avium complex infection (n = 7), CMV retinitis (n = 5), recurrent oroesophageal candidiasis (n = 5), Visceral leishmaniasis (n = 2), recurrent herpes zoster (n = 2), and chronic mucocutaneous herpes simplex infection (n = 1). In six individuals, OI prophylaxis was discontinued for two or more entities. Only two episodes of OI were recorded in these individuals during 18 months of follow-up. One developed tuberculous lymphadenitis despite having a good response to treatment, and another suffered a new episode of PCP after voluntary treatment interruption for 6 weeks. CONCLUSION: Secondary prophylaxis for OI can be attempted without major risk in HIV-infected patients experiencing a favourable response to HAART. The benefit of this intervention should reduce costs, drug side-effects and pharmacologic interactions, and indirectly will improve patient's quality of life and adherence to antiretroviral treatment.     

Assessing baseline religious practices and beliefs to predict adherence to highly active antiretroviral therapy among HIV-infected persons

The efficacy of highly active antiretroviral therapy (HAART) is dependent upon moderately high levels of adherence; however, predicting adherence before HAART initiation can be difficult. We conducted a prospective, longitudinal study among 350 HIV-infected adults attending a HIV clinic in San Diego, CA (USA) from January 2010 to December 2011 to examine both established and novel predictors of adherence, including religious practices and beliefs. Statistically significant (p < .05) variables identified in bivariate analyses were included in multivariate analyses predicting ≥90% adherence. Higher annual household income (p = .004) and religious affiliation (p = .031) were predictive of greater adherence. Participants who said their beliefs gave meaning to their lives, made them feel they had a connection with a higher being, were influential during their recovery, and helped them feel connected to humanity were more likely to be ≥90% adherent (p < .015). Conversely, participants who believed God created all things in the universe; that God will not turn his back on them; and those who regularly attended religious services, participated in religious rituals, and prayed and meditated to get in touch with God were less likely to be ≥90% adherent (p ≤ .025). Results indicate that a patient's religious beliefs and practices may predict medication adherence. Interventions should be designed to emphasize the use of positive religious coping strategies and address the adverse implications of religious fatalism.     

Predictors of immunological failure after initial response to highly active antiretroviral therapy in HIV-1-infected adults: a EuroSIDA study

BACKGROUND: Factors that determine the immunological response to highly active antiretroviral therapy (HAART) are poorly defined. OBJECTIVE: Our aim was to investigate predictors of immunological failure after initial CD4(+) response. METHODS: Data were from EuroSIDA, a prospective, international, observational human immunodeficiency virus (HIV) type 1 cohort. RESULTS: Of 2347 patients with an increase in CD4(+) cell count >or=100 cells/microL within 6-12 months of the initiation of HAART, 550 (23%) subsequently experienced immunological failure (CD4(+) count less than or equal to the pre-HAART value). The incidence of failure was 11.6 incidences/100 person-years of follow-up (95% confidence interval [CI], 10.2-13.4) during the first 12 months and decreased significantly over time (P<.0001). Independent predictors of immunological failure were pre-HAART CD4(+) cell count (per 50% higher; relative hazard [RH], 2.05; 95% CI, 1.83-2.31; P<.0001), time-updated virus load (per 1 log(10) higher; RH, 1.77; 95% CI, 1.64-1.92; P<.0001), and HIV-1 risk behavior (P=.047 for a global comparison of risk groups). CONCLUSION: The risk of immunological failure in patients with an immunological response to HAART diminishes with a longer time receiving treatment and is associated with pretreatment CD4(+) cell count, ongoing viral replication, and intravenous drug use.