Intrathecal Drug Delivery Systems (IDDS): The Implantable Systems Performance Registry (ISPR).

OBJECTIVES: The ISPR was initially created to monitor the product performance of Medtronic implanted intrathecal drug infusion and spinal cord systems available in the United States. MATERIALS AND METHODS: Data were collected from 50 representative sites implanting and following patients with intrathecal drug delivery systems across the United States between August 7, 2003 and January 31, 2014. Device performance over time was estimated using life table survival methods. RESULTS: Of the 6093 patients enrolled in the ISPR, 3405 (55.9%) were female and 2675 (43.9%) were male, and 13 (0.2%) did not provide gender data. The average age at enrollment was 52.9 years (SD =17.6 years) and average follow-up time was 29.6 months. Currently, the estimates of device survival from pump-related events exceed 90% for all pump models across the applicable follow-up time points. The majority of product performance events were catheter-related. At 5 years of follow-up, all applicable catheter models, with the exception of revised not as designed or grafted not as designed catheters, had greater than 81% survival from catheter-related events. CONCLUSIONS: The ISPR is designed to serve as an ongoing source of system and device-related information with a focus on "real-world" safety and product performance. ISPR data continue to be used to guide future product development efforts aimed at improving product reliability and quality.

Spinal Cord Stimulation (SCS)-The Implantable Systems Performance Registry (ISPR).

OBJECTIVES: The Implantable Systems Performance Registry (ISPR) was created to monitor the product performance of Medtronic Spinal Cord Stimulation (SCS) and implanted intrathecal drug infusion systems available in the United States. MATERIALS AND METHODS: Data were collected on 2605 patients from 44 centers from various geographic regions across the United States implanting and following patients with SCS systems between June 25, 2004 and January 31, 2014. Actuarial life table methods are used to estimate device performance over time. Of the 2605 patients, 1490 (57.2%) were female, 1098 (42.1%) were male and 17 (0.7%) did not provide gender data. The average age at enrollment was 56.3 years (range: 4-97, SD = 14.3) and average follow-up time was 20.1 months (SD = 22.5). RESULTS: Currently the estimates of device survival from neurostimulator-related events exceed 97% for all neurostimulator models across the applicable follow-up time points and all applicable extension models had greater than 95% survival from extension events. The majority of product performance events were lead-related. At 5 years of follow-up, all applicable lead families, with the exception of the Pisces-Quad LZ family, had greater than 75% survival from lead events. CONCLUSIONS: The ISPR is designed to serve as an ongoing source of system and device-related information with a focus on "real-world" safety and product performance. ISPR data continue to be used to guide future product development efforts aimed at improving product reliability and quality.

Relationship between inflammatory and coagulation biomarkers and cardiac autonomic function in HIV-infected individuals.

AIM: To examine the relationship between inflammatory and coagulation biomarkers and cardiac autonomic function (CAF) as measured by heart rate variability in persons with HIV. MATERIALS & METHODS: This analysis included 4073 HIV-infected persons from the Strategies for Management of Antiretroviral Therapy study. We examined the association between IL-6, high-sensitivity C-reactive protein (hsCRP) and D-dimer with heart rate variability measures (SDNN and rMSSD), both cross-sectionally and longitudinally. RESULTS: Cross-sectional analysis revealed significant inverse associations between IL-6, hsCRP and d-dimer with SDNN and rMSSD (p < 0.01 for all comparisons). However, longitudinal analysis failed to show a significant association between baseline IL-6, hsCRP and d-dimer with change in CAF over time. CONCLUSION: Cross-sectionally, higher levels of inflammatory and coagulation biomarkers were associated with lower levels of CAF in the Strategies for Management of Antiretroviral Therapy trial. Although deterioration in CAF was observed during followup, baseline levels of inflammatory and coagulation markers were not predictive of the decline in CAF over time.

Race/ethnicity and HAART initiation in a military HIV infected cohort.

BACKGROUND: Prior studies have suggested that HAART initiation may vary by race/ethnicity. Utilizing the U.S. military healthcare system, which minimizes confounding from healthcare access, we analyzed whether timing of HAART initiation and the appropriate initiation of primary prophylaxis among those at high risk for pneumocystis pneumonia (PCP) varies by race/ethnicity. METHODS: Participants in the U.S. Military HIV Natural History Study from 1998-2009 who had not initiated HAART before 1998 and who, based on DHHS guidelines, had a definite indication for HAART (CD4 <200, AIDS event or severe symptoms; Group A), an indication to consider HAART (including CD4 <350; Group B) or electively started HAART (CD4 >350; Group C) were analyzed for factors associated with HAART initiation. In a secondary analysis, participants were also evaluated for factors associated with starting primary PCP prophylaxis within four months of a CD4 count <200 cells/mm3. Multiple logistic regression was used to compare those who started vs. delayed therapy; comparisons were expressed as odds ratios (OR). RESULTS: 1262 participants were evaluated in the analysis of HAART initiation (A = 208, B = 637, C = 479 [62 participants were evaluated in both Groups A and B]; 94% male, 46% African American, 40% Caucasian). Race/ethnicity was not associated with HAART initiation in Groups A or B. In Group C, African American race/ethnicity was associated with lower odds of initiating HAART (OR 0.49, p = 0.04). Race and ethnicity were also not associated with the initiation of primary PCP prophylaxis among the 408 participants who were at risk. CONCLUSIONS: No disparities in the initiation of HAART or primary PCP prophylaxis according to race/ethnicity were seen among those with an indication for therapy. Among those electively initiating HAART at the highest CD4 cell counts, African American race/ethnicity was associated with decreased odds of starting. This suggests that free healthcare can potentially overcome some of the observed disparities in HIV care, but that unmeasured factors may contribute to differences in elective care decisions.

Determinants of developing widened spatial QRS-T angle in HIV-infected individuals: results from the Strategies for Management of Antiretroviral Therapy [SMART] Study.

BACKGROUND: A widened electrocardiographic spatial QRS-T angle has been shown to be predictive of cardiovascular disease in HIV-infected individuals. However, determinants and risk factors of developing widened QRS-T angle over time in this population remain unknown. METHODS AND RESULTS: Spatial QRS-T angle was automatically measured from standard electrocardiogram of 1444 HIV-infected individuals without baseline widened spatial QRS-T angle from the Strategies for Management of Antiretroviral Therapy [SMART], a clinical trial comparing two antiretroviral treatment strategies [Drug Conservation (DC) vs. Viral Suppression (VS)]. Conditional logistic regression analysis was used to examine the association between baseline characteristics and incident widened spatial QRS-T angle (a new angle>93° in males and>74° in females). During 2544 person-years of follow-up, 199 participants developed widened angle at a rate of 7.8 per 100 person-years. In unadjusted models, female sex, black race (vs. white), DC treatment strategy, current and past smokers (vs. never), history of alcohol abuse, greater body mass index, history of diabetes and higher levels of hs-C-reactive protein were associated with incident widened spatial QRS-T angle. When these variables were entered together in the same model with adjustment for demographics and treatment strategy, DC treatment strategy [OR (95% CI): 1.50 (1.09, 2.07)], female gender [1.69 (1.17, 2.45)], current and past smoking (vs. never) [2.49 (1.63, 3.81) and 1.93 (1.21, 3.09), respectively], and diabetes [2.28 (1.33, 3.91)] predicted incident widened spatial QRS-T angle. CONCLUSIONS: Drug conservation treatment strategy, female gender, smoking, and diabetes are independently predictive of incident widened spatial QRS-T angle in HIV-infected individuals.

Improved neurocognitive test performance in both arms of the SMART study: impact of practice effect.

We evaluated factors associated with improvement in neurocognitive performance in 258 HIV-infected adults with baseline CD4 lymphocyte counts above 350 cells/mm³ randomized to intermittent, CD4-guided antiretroviral therapy (ART) (128 participants) versus continuous therapy (130) in the Neurology substudy of the Strategies for Management of Antiretroviral Therapy trial. Participants were enrolled in Australia, North America, Brazil, and Thailand, and neurocognitive performance was assessed by a five-test battery at baseline and month 6. The primary outcome was change in the quantitative neurocognitive performance z score (QNPZ-5), the average of the z scores of the five tests. Associations of the 6-month change in test scores with ART use, CD4 cell counts, HIV RNA levels, and other factors were determined using multiple regression models. At baseline, median age was 40 years, median CD4 cell count was 513 cells/mm³, 88 % had plasma HIV RNA ≤ 400 copies/mL, and mean QNPZ-5 was -0.68. Neurocognitive performance improved in both treatment groups by 6 months; QNPZ-5 scores increased by 0.20 and 0.13 in the intermittent and continuous ART groups, respectively (both P < 0.001 for increase and P = 0.26 for difference). ART was used on average for 3.6 and 5.9 out of the 6 months in the intermittent and continuous ART groups, respectively, but the increase in neurocognitive test scores could not be explained by ART use, changes in CD4, or plasma HIV RNA, which suggests a practice effect. The impact of a practice effect after 6 months emphasizes the need for a control group in HIV studies that measure intervention effects using neurocognitive tests similar to ours.

Protease inhibitors and cardiac autonomic function in HIV-infected patients: a cross-sectional analysis from the Strategies for Management of Antiretroviral Therapy (SMART) Trial.

OBJECTIVE: To compare cardiac autonomic function as measured by heart rate variability for HIV-infected participants taking protease inhibitors (PIs) with those taking a non-nucleoside reverse transcriptase inhibitor without a PI (NNRTI-no PI) regimen. DESIGN: Cross-sectional analysis. SETTING: Multicentre study. PARTICIPANTS: 2998 participants (average age 44 years, 28% females) enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) trial. PRIMARY OUTCOME MEASURES: Heart rate and two heart rate variability measures (the SD of all filtered RR intervals over the length of the recording (SDNN) and the root mean square of successive differences in normal RR intervals (rMSSD)). RESULTS: At study entry, 869 participants were taking a boosted PI (PI/r), 579 a non-boosted PI and 1550 an NNRTI-no PI. Median values (IQR) of heart rate, SDNN and rMSSD were: 68 (60-75) beats/min (bpm), 21 (13-33) ms, 22 (13-35) ms in the PI/r group, 68 (60-75) bpm, 21 (13-33) ms and 21 (14-33) ms in the non-boosted PI group and 69 (62-77) bpm, 20 (13-31) ms and 21(13-33) ms in the NNRTI-no PI group. After adjustment for baseline factors, for those given PI/r and non-boosted PI, heart rate was 2.2 and 2.8 bpm, respectively, lower than the NNRTI-no PI group (p<0.001 for both). On the other hand, compared with the NNRTI-no PI group, log SDNN and log rMSSD were significantly greater for those in the non-boosted PI (p values for baseline adjusted differences in log-transformed SDNN and rMSSD were 0.004 and 0.001) but not for those in the PI/r group at the 0.01 α-level. CONCLUSIONS: Compared to an NNRTI-no PI regimen, heart rate was lower for those taking a PI/r or non-boosted PI and heart rate variability was greater, reflecting better cardiac autonomic function, for those taking a non-boosted PI regimen but not PI/r.

Electrocardiographic spatial QRS-T angle and incident cardiovascular disease in HIV-infected patients (from the Strategies for the Management of Antiretroviral Therapy [SMART] study).

Widening of the electrocardiographic (ECG) spatial QRS-T angle has been predictive of cardiovascular disease (CVD) events in the general population. However, its prognostic significance in human immunodeficiency virus (HIV)-infected patients remains unknown. The spatial QRS-T angle was derived from the baseline resting 12-lead electrocardiogram of 4,453 HIV-infected patients aged 43.5 ± 9.3 years from the Strategies for Management of Antiretroviral Therapy (SMART) trial. CVD events were identified during a median follow-up of 28.7 months. Quartiles of the spatial QRS-T angle was calculated for men and women separately, and values in the upper quartile were considered as a widened angle (values >74° for women and >93° for men). A multivariate Cox proportional hazards analysis was used to examine the association between a widened baseline spatial QRS-T angle and incident CVD events. During 11,965 person-years of follow-up, 152 CVD events occurred at a rate of 1.27 events/100 person-years. The rate of CVD events in those with a widened spatial QRS-T angle was almost double the rate in those with a normal spatial QRS-T angle (rate ratio 1.94, 95% confidence interval 1.40 to 2.69; p <0.001). In a model adjusted for study treatment arm, demographics, CVD risk factors, HIV characteristics, inflammatory markers, and other ECG abnormalities, a widened spatial QRS-T angle was associated with a >50% increased risk of CVD events compared to a normal spatial QRS-T angle (hazard ratio 1.53, 95% confidence interval 1.07 to 2.17; p = 0.02). No interaction was seen by SMART trial arm (p value for interaction = 0.37) or gender (p value for interaction = 0.84). In conclusion, a widened spatial QRS-T angle was independently predictive of CVD events in HIV-infected patients receiving antiretroviral therapy. This highlights the potential role of routine electrocardiography as a simple noninvasive CVD risk-screening tool in HIV-infected patients.

Hepatitis B virus coinfection negatively impacts HIV outcomes in HIV seroconverters.

BACKGROUND: Understanding the impact of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) coinfection has been limited by heterogeneity of HIV disease. We evaluated HBV coinfection and HIV-related disease progression in a cohort of HIV seroconverters. METHODS: Participants with HIV diagnosis seroconversion window of ≤ 3 years and serologically confirmed HBV infection (HB) status were classified at baseline into 4 HB groups. The risk of clinical AIDS/death in HIV seroconverters was calculated by HB status. RESULTS: Of 2352 HIV seroconverters, 474 (20%) had resolved HB, 82 (3%) had isolated total antibody to hepatitis B core antigen (HBcAb), and 64 (3%) had chronic HB. Unadjusted rates (95% confidence intervals [CIs]) of clinical AIDS/death for the HB-negative, resolved HB, isolated HBcAb, and chronic HB groups were 2.43 (2.15-2.71); 3.27 (2.71-3.84); 3.75 (2.25-5.25); and 5.41 (3.41-7.42), respectively. The multivariable risk of clinical AIDS/death was significantly higher in the chronic HB group compared to the HB-negative group (hazard ratio [HR], 1.80; 95% CI, 1.20-2.69); while the HRs were increased but nonsignificant for those with resolved HB (HR, 1.17; 95% CI, .94-1.46) and isolated HBcAb (HR, 1.14; 95% CI, .75-1.75). CONCLUSIONS: HBV coinfection has a significant impact on HIV outcomes. The hazard for an AIDS or death event is almost double for those with chronic HB compared, with HIV-monoinfected persons.

Development of chronic hepatitis B virus infection in hepatitis B surface antigen negative HIV/HBV co-infected adults: a rare opportunistic illness.

Changes in serologic status in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infected individuals with either isolated anti-HBc or resolved HBV infection have been reported, but the frequency of clinically meaningful long-term serologic changes is not well-defined. This study therefore, examined longitudinal serologic status for hepatitis B surface antigen (HBsAg)-negative HIV/HBV co-infected participants in a large cohort. Among 5,222 cohort participants, 347 (7%) were initially isolated anti-HBc positive, and 1,073 (21%) had resolved HBV infection (concurrently reactive for anti-HBc and anti-HBs). Thirty-three (10%) of the 347 participants with isolated anti-HBc were later positive for HBsAg at least once, compared with 3 (0.3%) of those with resolved HBV (P < 0.001). A total of 14 participants became persistently positive for HBsAg and were thus classified as having late-onset chronic HBV infection at a median of 3.7 years after initial HBV diagnosis. For those initially with HBsAg-negative HIV/HBV co-infection, the rate of late-onset chronic HBV infection was 1.39/1,000 person-years. Those with late-onset chronic HBV infection experienced significant decreases in CD4 cell counts (P = 0.002) with a mean of 132 cells/µl at the time of late-onset chronic HBV infection, but no factor distinguished those who were positive for HBsAg only once from those that developed late-onset chronic HBV infection. Over a median of 2.9 years following late-onset chronic HBV infection, 3 of 14 subsequently lost HBsAg. The occurrence of late-onset chronic HBV infection in HBsAg negative HIV/HBV co-infected adults appears to be one important, albeit rare, clinical event seen almost exclusively in those with isolated anti-HBc and low CD4 cell count.

Long-term safety and serologic response to measles, mumps, and rubella vaccination in HIV-1 infected adults.

We analyzed HIV viral load (VL) and CD4 count changes, and antibody responses following MMR vaccination of individuals in the U.S. Military HIV Natural History Study cohort. Cases receiving at least one dose of MMR vaccine after HIV diagnosis were matched 1:2 to HIV-positive controls not receiving the vaccine. Baseline was defined as time of vaccination for cases and indexed and matched to the time post-HIV diagnosis for controls. Changes in CD4 count and VL at 6, 12, 18 and 24 months were compared between cases and controls using a general linear model. Available sera from cases were tested for MMR seropositivity at baseline and post-vaccination at 6, 12, 18, and 24 months. Overall mean CD4 count change from baseline through 24 months was 20 (±23) cells/µL greater for cases than controls (p=0.39). Similar non-significant changes in CD4 cell count were seen in the subset of those not on HAART at baseline. VL changes were small and similar between groups (mean differential change -0.04 (±0.18) log(10) copies/mL; p=0.84). Of 21 vaccinated participants with baseline serologic testing, 14 (67%) were reactive to measles, 19 (91%) to mumps, and 20 (95%) to rubella. Three (43%) of 7 participants nonreactive to measles developed measles IgG; for mumps, 1 (50%) of 2 developed mumps IgG; for rubella, 1 (100%) developed rubella IgG. MMR vaccination did not result in detrimental immunologic or virologic changes through 24 months post-vaccination.

Boosted protease inhibitors and the electrocardiographic measures of QT and PR durations.

BACKGROUND: There are contradictory reports regarding the effects of protease inhibitors on the ECG measures of QT and PR interval durations. The effect of interrupting use of protease inhibitors on QT and PR progression is also unknown. METHODS: This analysis included 3719 participants from the Strategies for Management of Antiretroviral Therapy (SMART) study, of whom 1879 were randomized to receive intermittent antiretroviral therapy (ART) (drug conservation group), whereas the rest received these drugs continuously (viral suppression group). Linear regression analysis was used to compare four ritonavir-boosted protease inhibitor (protease inhibitor/r) regimens [saquinavir (SQV/r), lopinavir (LPV/r), atazanavir (ATV/r), and other protease inhibitor/r], and nonboosted protease inhibitor regimens with nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens for Bazett's (QTcB) and Fredericia's (QTcF) heart rate corrected QT and PR. Changes in QTcB, QTcF, and PR after 12 and 24 months of randomization were compared in the drug conservation group and viral suppression group. RESULTS: Average levels of QTcB, QTcF, and PR duration at entry were 415, 406, and 158 ms. At study entry, 49% of participants were taking an NNRTI (no protease inhibitor)-based regimen and 31% were prescribed a boosted protease inhibitor, the most common being LPV/r. After adjustment for baseline factors, QTcB and QTcF levels did not vary by boosted protease inhibitor group (P = 0.26 and P = 0.34, respectively). For those given any of the boosted protease inhibitors, QTcB was 1.5 ms lower than the NNRTI group (P = 0.04). Both boosted and nonboosted protease inhibitor-containing regimens were significantly associated (P < 0.01 for each) with longer PR intervals compared to the NNRTI group. After adjustment, the difference between boosted protease inhibitors and the NNRTI group was 5.11 ms (P < 0.01); for nonboosted protease inhibitors, this difference was 3.00 ms (P < 0.01). Following ART interruption, PR duration declined for both the boosted and nonboosted protease inhibitor groups and compared to the viral suppression group, significant changes in PR interval were observed 24 months after ART interruption of boosted protease inhibitors (P < 0.01). CONCLUSION: Different protease inhibitor-based regimens have a similar, minimal effect on QT compared to NNRTI-based regimens. All protease inhibitor-based regimens (boosted and nonboosted) were associated with prolongation of PR, and interruption of protease inhibitor regimens reduced the prolonged PR duration. Further research is needed to confirm the findings of this study and assess the clinical relevance of the differences.

Prevalence and prognostic significance of ECG abnormalities in HIV-infected patients: results from the Strategies for Management of Antiretroviral Therapy study.

BACKGROUND: It remains debated whether to include resting electrocardiogram (ECG) in the routine care of human immunodeficiency virus (HIV)-infected patients. METHODS: This analysis included 4518 HIV-infected patients (28% women and 29% blacks) from the Strategies for Management of Antiretroviral Therapy study, a clinical trial aimed to compare 2 HIV treatment strategies. ECG abnormalities were classified using the Minnesota Code. Cox proportional hazards analysis was used to examine the association between baseline ECG abnormalities and incident cardiovascular disease (CVD). RESULTS: More than half of the participants (n = 2325, or 51.5%) had either minor or major ECG abnormalities. Minor ECG abnormalities (48.6%) were more common than major ECG abnormalities (7.7%). During a median follow-up of 28.7 months, 155 participants (3.4%) developed incident CVD. After adjusting for the study-treatment arms, the presence of major, minor, and either minor or major ECG abnormalities was significantly predictive of incident CVD (hazard ratio [95% confidence interval]: 2.76 [1.74-4.39], P < .001; 1.58 [1.14-2.20], P = .006; 1.57 [1.14-2.18], P = .006, respectively). However, after adjusting for demographics, CVD risk factors, and HIV characteristics (full model), presence of major ECG abnormalities were still significantly predictive of CVD (1.83 [1.12-2.97], P = .015) but not minor or major abnormalities taken together (1.26 [0.89-1.79], P = .18; 1.25 [0.89-1.76], P = .20, respectively). Individual ECG abnormalities that significantly predicted CVD in the fully adjusted model included major isolated ST-T abnormalities, major prolongation of QT interval, minor isolated ST-T, and minor isolated Q-QS abnormalities. CONCLUSION: Nearly 1 in 2 of the HIV-infected patients in our study had ECG abnormalities; 1 in 13 had major ECG abnormalities. Presence of ECG abnormalities, especially major ECG abnormalities, was independently predictive of incident CVD. These results suggest that the ECG could provide a convenient risk-screening tool in HIV-infected patients.

Natural history of colonization with gram-negative multidrug-resistant organisms among hospitalized patients.

OBJECTIVE: To determine the anatomic sites and natural history of colonization with gram-negative multidrug-resistant organisms (MDROs). DESIGN: Prospective, longitudinal cohort study. SETTING: Walter Reed Army Medical Center, a 236-bed tertiary care center in Washington, DC. PATIENTS: Deployed subjects (ie, inpatients medically evacuated from Iraq or Afghanistan) or nondeployed subjects admitted to the same hospital. METHODS: Consenting patients had 6 anatomic sites cultured every 3 days for 2 weeks and then weekly. Gram-negative organisms resistant to 3 or more classes of antibiotics were considered MDROs. Isolates were genotyped using pulsed-field gel electrophoresis. Clinical data, data on antibiotic use, and clinical culture results were collected. RESULTS: Of 60 deployed subjects, 14 (23%) were colonized with an MDRO at admission, and 13 (22%) had incident colonization during hospitalization. The groin was the most sensitive anatomic site for detecting MDRO colonization, and all but one subject remained colonized for the duration of their hospitalization. Sixty percent of subjects with incident Acinetobacter colonization and 25% of subjects with incident Klebsiella colonization had strains that were related to those isolated from other subjects. Of 60 nondeployed subjects, 5 (8%) were colonized with an MDRO at admission; all had recent healthcare contact, and 1 nondeployed subject had an isolate related to a strain recovered from a deployed subject. CONCLUSIONS: Colonization with gram-negative MDROs is common among patients with war-related trauma admitted to a military hospital and also occurs among nondeployed patients with recent healthcare contact. The groin is the most sensitive anatomic site for active surveillance, and spontaneous decolonization is rare.

Pneumonia in HIV-infected persons: increased risk with cigarette smoking and treatment interruption.

RATIONALE: Bacterial pneumonia is a major cause of morbidity for HIV-infected persons and contributes to excess mortality in this population. OBJECTIVES: To evaluate the frequency and risk factors for occurrence of bacterial pneumonia in the present era of potent antiretroviral therapy. METHODS: We evaluated data from a randomized trial of episodic antiretroviral therapy. The study, Strategies for Management of Antiretroviral Therapy, enrolled 5,472 participants at 318 sites in 33 countries. Study patients had more than 350 CD4 cells at baseline. Diagnosis of bacterial pneumonia was confirmed by a blinded clinical-events committee. MEASUREMENTS AND MAIN RESULTS: During a mean follow-up of 16 months, 116 participants (2.2%) developed at least one episode of bacterial pneumonia. Patients randomized to receive episodic antiretroviral therapy were significantly more likely to develop pneumonia than patients randomized to receive continuous antiretroviral therapy (hazard ratio, 1.55; 95% confidence interval, 1.07-2.25; P = 0.02). Cigarette smoking was a major risk factor: Current-smokers had more than an 80% higher risk of pneumonia compared with never-smokers (hazard ratio, 1.82; 95% confidence interval, 1.09-3.04; P = 0.02). Participants who were on continuous HIV treatment and were current smokers were three times more likely to develop bacterial pneumonia than nonsmokers. Current smoking status was significant, but a past history of smoking was not. CONCLUSIONS: Bacterial pneumonia is a major source of morbidity, even for persons on potent antiretroviral therapy, including those with high CD4 cells. Efforts to reduce this illness should stress the importance of uninterrupted antiretroviral therapy and attainment and/or maintenance of nonsmoking status.

The impact of episodic CD4 cell count-guided antiretroviral therapy on quality of life.

OBJECTIVE: To evaluate the effect of episodic antiretroviral therapy on quality of life (QOL). DESIGN: This was a substudy of the Strategies of Management of Antiretroviral Therapy study, in which patients were randomized to continuous versus CD4 cell count-guided episodic antiretroviral therapy. QOL assessments included an analog scale for current health and the Short-Form 12 Item Survey, a standard abbreviated QOL instrument. RESULTS: A total of 1225 patients had QOL assessments over a mean follow-up time of 2.4 years. Most (76%) were on antiretroviral therapy at enrollment; the median CD4 lymphocyte count was 575 (interquartile range: 455 to 784) cells/mm3; and mean current health was 75 on a scale from 0 to 100, and 50% reported very good or excellent general health. Through follow-up, whenever QOL outcomes differed, the results were inferior among patients in the episodic therapy group compared with the continuous therapy group (current health, Physical Health Component Score [both P = 0.05], general health perceptions, physical functioning, and energy [all P = 0.03]). HIV disease progression (opportunistic disease or death) was more common in the episodic therapy arm and was preceded by marked declines in QOL, but excluding participants with disease progression had minimal effect on QOL comparisons. CONCLUSION: CD4 count-guided episodic use of antiretroviral therapy resulted in inferior QOL compared with continuous therapy.