Summary

The incidence of and risk factors for community-acquired pneumonia (CAP) are described from 2000–2005 in a multicenter US cohort of HIV-infected children. In 736 patients, 87 episodes of CAP (33.2 events/1,000 PY) had a mean CD4% of 23% (controls: 30%) and mean CD4 count of 668 cells/mm3 (controls: 870 cells/mm3). CAP incidence decreased 44% from 2000–2001 to 2002–2005. On multivariate analysis, viral load ≥100,000 copies/mL (OR 3.98; CI: 1.05–15.13) was associated with CAP. Herd immunity through pneumococcal immunization may have diluted the effect of individual immunization in this cohort.

Objective

Geographic location may be related to the receipt of quality HIV healthcare services. Clinical outcomes and healthcare utilization were evaluated in rural, urban and peri-urban patients seen at high-volume U.S. urban-based HIV care sites.

Methods

Zip codes for 8,773 HIV patients followed in 2005 at 7 HIV Research Network sites were categorized as rural (population<10K), peri-urban (10K – 100K) and urban (>100K). Clinical and demographic characteristics, inpatient and outpatient (OP) utilization, AIDS defining illness rates, receipt of highly active antiretroviral therapy (HAART), opportunistic infection (OI) prophylaxis usage and virologic suppression were compared among patients, using Χ2 tests for categorical variables, t-tests for means, and logistic regression for HAART utilization.

Results

HIV-infected rural (n=170) and peri-urban (n=215) patients were less likely to be Black or Hispanic than urban HIV patients. Peri-urban subjects were more likely to report MSM as their HIV risk factor than rural or urban subjects. Age, gender, CD4 or HIV-RNA distribution, virologic suppression, HAART usage or OI prophylaxis did not differ by geographic location. In multivariate analysis, rural and peri-urban patients were less likely to have ≥4 annual outpatient visits than urban patients. Rural patients were less likely to receive HAART if they were Black. Overall, geographic location (as defined by home zip code) did not affect receipt of HAART or OI prophylaxis.

Conclusion

Although demographic and healthcare utilization differences were seen among rural, peri-urban, and urban HIV patients, most HIV outcomes and medication use were comparable across geographic areas. As with HIV care for urban-dwelling patients, areas for improvement for non-urban HIV patients include access to HAART among minorities and IDUs.

Background

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).

Objective

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.

Design

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.

Setting

U.S. HIV outpatient clinics.

Patients

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.

Measurements

Annual rates of antiretroviral therapy use, HIV VL, and CD4 cell count at death.

Results

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).

Limitation

The usual limitations of observational data apply.

Conclusion

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.

Objectives

Since 2003, U.S. organizations have recommended universal screening, rather than targeted screening, of HIV-infected persons for gonorrhea (NG) and Chlamydia (CT). Our objective was to determine whether wider testing resulting from these guidelines would produce an increase in NG/CT diagnoses.

Methods

We studied 3,283 patients receiving HIV care 1999–2007 in the Johns Hopkins Hospital HIV clinic. The two primary outcomes were: 1) the occurrence of any NG/CT testing in each year of care and 2) the occurrence of any positive result(s) in years of testing. The proportion of all patients in care who were diagnosed with NG/CT was defined as the number of patients with positive results divided by the number of patients in care. Trends were analyzed with repeated measures logistic regression.

Results

The proportion of patients tested for NG/CT increased steadily from 0.12 in 1999 to 0.33 in 2007 (OR per year for being tested, 1.17 [1.15, 1.19]). The proportion positive among those tested decreased significantly after 2003 (OR per year 0.67 [0.55, 0.81]). The proportion of all patients in care diagnosed with NG/CT therefore remained generally stable 1999–2007 (OR per year 0.97 [0.91, 1.04]).

Conclusions

Universal annual screening, as implemented, did not increase the proportion of all patients in care who were diagnosed with NG/CT. Similarly low implementation rates have been reported in cross-sectional studies. If future efforts to enhance implementation do not yield increases in diagnoses, then guidelines focusing on targeted screening of high risk groups rather than universal screening may be warranted.

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.

HIV is no longer a contraindication to transplantation. For HIV-infected patients, HIV-infected deceased donors (HIVDD) could attenuate the organ shortage and waitlist mortality. However, this practice would violate United States federal law. The goal of this study was to estimate the potential impact of legalizing transplantation of HIV-infected organs by quantifying the potential pool of HIVDD. Using Nationwide Inpatient Sample (NIS) data, HIV-infected deaths compatible with donation were enumerated. Using HIV Research Network (HIVRN) data, CD4 count, plasma HIV-1 RNA level, AIDS-defining illnesses, and causes of death were examined in potential HIVDD. Using UNOS data, evaluated donors who later demonstrated unanticipated HIV infections were studied. From NIS, a yearly average of 534 (range: 481–652) potential HIVDD were identified, with 63 (range: 39–90) kidney-only, 221 (range: 182–255) liver-only, and 250 (range: 182–342) multi-organ donors. From HIVRN, a yearly average of 494 (range: 441–533) potential HIVDD were identified. Additionally, a yearly average of 20 (range: 11–34) donors with unanticipated HIV-infection were identified from UNOS. Deceased HIV-infected patients represent a potential of approximately 500–600 donors per year for HIV-infected transplant candidates. In the current era of HIV management, a legal ban on the use of these organs seems unwarranted and likely harmful.

Objective

We examined whether having a psychiatric disorder among HIV-infected individuals is associated with differential rates of discontinuation of HAART and whether the number of mental health visits impact these rates.

Design

This longitudinal study (fiscal year: 2000–2005) used discrete time survival analysis to evaluate time to discontinuation of HAART. The predictor variable was presence of a psychiatric diagnosis (serious mental illness versus depressive disorders versus none).

Setting

Five United States outpatient HIV sites affiliated with the HIV Research Network. Patients: The sample consisted of 4989 patients. The majority was nonwhite (74.0%) and men (71.3%); 24.8% were diagnosed with a depressive disorder, and 9% were diagnosed with serious mental illness.

Main outcome measures

Time to discontinuation of HAART adjusting for demographic factors, injection drug use history, and nadir CD4 cell count.

Results

Relative to those with no psychiatric disorders, the hazard probability for discontinuation of HAART was significantly lower in the first and second years among those with SMI [adjusted odds ratio: first year, 0.57 (0.47–0.69); second year, 0.68 (0.52–0.89)] and in the first year among those with depressive disorders [adjusted odds ratio: first year, 0.61 (0.54–0.69)]. The hazard probabilities did not significantly differ among diagnostic groups in subsequent years. Among those with psychiatric diagnoses, those with six or more mental health visits in a year were significantly less likely to discontinue HAART compared with patients with no mental health visits.

Conclusion

Individuals with psychiatric disorders were significantly less likely to discontinue HAART in the first and second years of treatment. Mental health visits are associated with decreased risk of discontinuing HAART.

Objectives

Screening HIV-infected men for gonorrhea (GC) and Chlamydia (CT) may decrease HIV transmission and reduce the incidence of pelvic inflammatory disease in female partners. This study determined GC/CT testing rates in a clinical HIV cohort before and after 2003 when the U.S. Centers for Disease Control and Prevention issued guidelines for GC/CT screening.

Methods

First GC/CT testing episodes were identified for all men enrolling in a Baltimore HIV clinic 1999–2007. Multivariate Cox and logistic regression were used to assess clinical and demographic factors associated with being tested and with having a positive result.

Results

Among 1110 men, the rate of GC/CT testing upon clinic enrollment increased from 4.0% prior to 2003 to 16.5% afterward, and the rate of ever being tested increased from 34.2% to 49.1% (P <0.001 for both comparisons). Among men with same sex contact, 10% of first testing episodes included extragenital sites. Among the 342 men ever-tested, 5.2% had positive results on first testing. Predictors of testing included enrolling after 2003, younger age, frequent visits, and black race. Predictors of a positive test result included CD4 count ≥200 cells/mm3 and younger age.

Conclusions

GC/CT testing rates among men increased substantially after the 2003 guidelines but remain low. Disseminating existing evidence for GC/CT screening and promoting operational interventions to facilitate it are warranted.

Objective

Although co-occurring psychiatric disorders are highly prevalent among those with HIV, little is known about use of outpatient mental health services (MHS) and psychotropic medication in the HAART era.

Methods

During 2003, 951 patients were interviewed at 14 sites in the HIV Research Network. Patients were questioned about use of MHS and psychotropic medications. Logistic regression was used to identify socio-demographic and clinical factors associated with MHS and psychotropic medication utilization

Results

The sample characteristics were: 68% male, 52% Black, 14% Hispanic, median age 46 years (range 20-85), 69% were on HAART. Approximately 34% reported at least one MHS within 6 months and 37% reported use of psychotropic medication for a mental health condition. In multivariate logistic regression, MHS was greater among disabled patients (AOR: 2.39[1.53 – 3.72]), current (2.26[1.53 - 3.35]) and former drug users (1.84[1.24 - 2.73]) and those with more than seven primary care visits in the past 6 months. Blacks (0.61[0.41 – 0.92]) were significantly less likely to use MHS compared to Whites. Similarly, usage of psychotropic medications was greater among disabled patients (AOR:1.79[1.14- 2.82]), women (AOR 1.66[1.13-2.43]), ]) and those with more than seven primary care visits. Blacks (0.37[0.24-0.58)]), and Hispanics (0.39[0.22-0.72]) were less likely to use a psychotropic medication. HAART utilization was not associated with MHS or psychiatric medication use

Conclusions

In the HAART era, self reported rates of mental health service and psychotropic medication utilization are high. Blacks continue report lower use of MHS and psychotropic medication compared to Whites.

Objective

To determine the impact of age and initial HAART regimen class on virologic and immunologic response within 24 months after initiation.

Design

Pooled analysis of data from 19 prospective cohort studies in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).

Methods

Twelve thousand, one hundred and ninety-six antiretroviral-naive adults who initiated HAART between 1998 and 2008 using a boosted protease inhibitor-based regimen or a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen were included in our study. Discrete time-to-event models estimated adjusted hazard odds ratios (aHOR) and 95% confidence intervals (CIs) for suppressed viral load (≤500 copies/ml) and, separately, at least 100 cells/μl increase in CD4 cell count. Truncated, stabilized inverse probability weights accounted for selection biases from discontinuation of initial regimen class.

Results

Among 12 196 eligible participants (mean age = 42 years), 50% changed regimen classes after initiation (57 and 48% of whom initiated protease inhibitor and NNRTI-based regimens, respectively). Mean CD4 cell count at initiation was similar by age. Virologic response to treatment was less likely in those initiating using a boosted protease inhibitor [aHOR = 0.77 (0.73, 0.82)], regardless of age. Immunologic response decreased with increasing age [18–<30: ref; 30–<40: aHOR 0.92 (0.85, 1.00); 40–<50: aHOR = 0.85 (0.78, 0.92); 50–<60: aHOR = 0.82 (0.74, 0.90); ≥60: aHOR=0.74 (0.65, 0.85)], regardless of initial regimen.

Conclusion

We found no evidence of an interaction between age and initial anti-retroviral regimen on virologic or immunologic response to HAART; however, decreased immunologic response with increasing age may have implications for age-specific when-to-start guidelines.

Highly active antiretroviral treatment has resulted in dramatically increased life expectancy among patients with HIV infection who are now aging while receiving treatment and are at risk of developing chronic diseases associated with advanced age. Similarities between aging and the courses of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome suggest that HIV infection compresses the aging process, perhaps accelerating comorbidities and frailty. In a workshop organized by the Association of Specialty Professors, the Infectious Diseases Society of America, the HIV Medical Association, the National Institute on Aging, and the National Institute on Allergy and Infectious Diseases, researchers in infectious diseases, geriatrics, immunology, and gerontology met to review what is known about HIV infection and aging, to identify research gaps, and to suggest high priority topics for future research. Answers to the questions posed are likely to help prioritize and balance strategies to slow the progression of HIV infection, to address comorbidities and drug toxicity, and to enhance understanding about both HIV infection and aging.

The prevalence of HIV in patients over the age of 50 years is increasing. Although older patients may achieve equal or better virologic suppression at equal rates compared with younger patients, the immunologic bene3 t of highly active antiretroviral therapy (HAART) in older patients may be reduced compared with younger patients. Comorbidities are more common in older patients than younger patients and can impact management of HIV in these patients. Providers must be cognizant of drug-drug interactions and side effects of HAART regimens when selecting an antiretroviral regimen in older HIV patients. As the HIV-infected population ages, there is a growing need to better determine the ideal HAART regimen and timing of HAART initiation in older patients.

Background:

Initiatives to improve early detection and access to HIV services have increased over time. We assessed the immune status of patients at initial presentation for HIV care from 1997-2007 in 13 US and Canadian clinical cohorts.

Methods:

We analyzed data from 44,491 HIV-infected patients enrolled in the North American – AIDS Cohort Collaboration on Research and Design. We identified first presentation for HIV care as the time of first CD4+ T-lymphocyte (CD4) measurement and excluded patients who prior to this date had HIV RNA measurements, evidence of antiretroviral exposure, or a history of AIDS-defining illness. Trends in mean CD4 count (measured as cells/mm3) and 95% confidence intervals ([,]) were determined using linear regression adjusted for age, gender, race/ethnicity, HIV transmission risk and cohort.

Results:

Median age at first presentation for HIV care increased over time (range 40-43 years, p<0.01), while the proportion of patients with injection drug use HIV transmission risk decreased (26% to 14%, p<0.01) and heterosexual transmission risk increased (16% to 23%, p<0.01). Median CD4 at presentation increased from 256 (IQR: 96-455) to 317 (IQR: 135-517) in 1997 to 2007 (p<0.01). The proportion with a CD4 count ≥350 at first presentation also increased from 1997 to 2007 (38% to 46%, p=<0.01). The estimated adjusted mean CD4 count increased at a rate of 6 [5, 7] per year.

Conclusion:

CD4 count at first presentation for HIV care has increased annually over the past 11 years, but has remained <350 cells/mm3, suggesting the urgent need for earlier HIV diagnosis and treatment.

Objective

This study examines the frequency of inpatient hospitalization, the number of inpatient days, and factors associated with inpatient utilization in a multi-state HIV cohort between 2002 and 2007.

Design

A prospective cohort study of HIV-infected adults in care at 11 U.S. HIV primary and specialty care sites located in different geographic regions.

Methods

Demographic, clinical, and resource utilization data were collected from medical records for the years 2002–2007. Rates of resource use were calculated for number of hospital admissions, total inpatient days, and mean length of stay (LOS) per admission.

Results

Annual inpatient hospitalization rates significantly decreased from 35 to 27 per 100 persons from 2002 to 2007. The number of inpatient days per year significantly decreased over time, while mean LOS per admission was stable. Women, patients 50 years or older, Blacks, injection drug users, and patients without private insurance had higher hospitalization rates than their counterparts. Admission rates were lower for patients with high CD4 counts and low HIV-1 RNA levels.

Conclusion

Inpatient hospitalization rates and number of inpatient days decreased for HIV patients in this multi-state cohort between 2002 and 2007. Sociodemographic disparities in inpatient utilization persist.

Context

A large proportion of people with human immunodeficiency virus (HIV) infection enter care late in the HIV disease course. Late entry can increase expenditures for care.

Objective

To estimate direct medical care expenditures for HIV patients as a function of disease status at initial presentation to care. Late entry is defined as initial CD4 test result ≤200 cells/mm3, intermediate entry as initial CD4 counts >200, and ≤500 cells/mm3; and early entry as initial CD4 count >500.

Patients

The study included 8348 patients who received HIV primary care and who were newly enrolled between 2000 and 2006 at one of 10 HIV clinics participating in the HIV Research Network.

Design

We reviewed medical record data from 2000 to 2007. We estimated costs per outpatient visit and inpatient day, and monthly medication costs (antiretroviral and opportunistic illness prophylaxis). We multiplied unit costs by utilization measures to estimate expenditures for inpatient days, outpatient visits, HIV medications, and laboratory tests. We analyzed the association between cumulative expenditures and initial CD4 count, stratified by years in care.

Results

Late entrants comprised 43.1% of new patients. The number of years receiving care after enrollment did not differ significantly across initial CD4 groups. Mean cumulative treatment expenditures ranged from $27,275 to $61,615 higher for late than early presenters. After 7 to 8 years in care, the difference was still substantial.

Conclusions

Patients who enter medical care late in their HIV disease have substantially higher direct medical treatment expenditures than those who enter at earlier stages. Successful efforts to link patients with medical care earlier in the disease course may yield cost savings.

We assessed CD4 count at initial presentation for HIV care among ≥50-year-olds from 1997-2007 in 13 US and Canadian clinical cohorts and compared to <50-year-olds. 44,491 HIV-infected individuals in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were included in our study. Trends in mean CD4 count (measured as cells/mm3) and 95% confidence intervals ([,]) were determined using linear regression stratified by age category and adjusted for gender, race/ethnicity, HIV transmission risk and cohort. From 1997-2007, the proportion of individuals presenting for HIV care who were ≥50-years-old increased from 17% to 27% (p-value < 0.01). The median CD4 count among ≥50 year-olds was consistently lower than younger adults. The interaction of age group and calendar year was significant (p-value <0.01) with both age groups experiencing modest annual improvements over time (< 50-year-olds: 5 [4 , 6] cells/mm3; ≥50-year-olds: 7 [5 , 9] cells/mm3), after adjusting for sex, race/ethnicity, HIV transmission risk group and cohort; however, increases in the two groups were similar after 2000. A greater proportion of older individuals had an AIDS-defining diagnosis at, or within three months prior to, first presentation for HIV care compared to younger individuals (13% vs. 10%, respectively). Due to the increasing proportion, consistently lower CD4 counts, and more advanced HIV disease in adults ≥50-year-old at first presentation for HIV care, renewed HIV testing efforts are needed.

Background

Most HIV-infected persons in the US present to care with advanced disease and many discontinue therapy prematurely. We sought to evaluate gender and racial/ethnic disparities in life-years lost due to risk behavior, late presentation and early discontinuation of HIV care, and to compare these survival losses in HIV-infected persons with losses from high-risk behavior and HIV disease itself.

Methods

Using a state-transition model of HIV disease, we simulated cohorts of HIV-infected persons and compared them to non-infected individuals with similar demographic characteristics. We estimated non-HIV-related mortality using risk-adjusted standardized mortality ratios as well as years of life lost due to late presentation and early discontinuation of antiretroviral therapy (ART) for HIV infection. Data from the national HIV Research Network, stratified by gender and race/ethnicity, were used for estimating CD4 counts at ART initiation.

Results

In HIV-uninfected persons in the US with risk profiles similar to those with HIV, the projected life expectancy starting at age 33 was 34.58 years, compared to 42.91 years for the general US population. Those with HIV lost an additional 11.92 years if they received HIV care concordant with guidelines; late treatment initiation resulted in 2.60 additional years of life lost, while premature ART discontinuation led to 0.70 more years of life lost. Losses from late initiation and early discontinuation were greatest for Hispanics (3.90 years).

Conclusions

The high-risk profile of HIV-infected persons, HIV infection itself, as well as late initiation and early discontinuation of care, all lead to substantial decreases in life expectancy. Survival disparities from late initiation and early discontinuation are most pronounced for Hispanic HIV-infected men and women. Interventions focused on risk behaviors as well as earlier linkage and better retention in care will lead to improved survival of HIV-infected persons in the US.

Background

Although combination antiretroviral therapy continues to evolve, with potentially more effective options emerging each year, the ability of therapy to prevent multiple regimen failure and mortality in clinical practice remains poorly defined.

Methods

Sixteen cohorts representing over 60 sites contributed data on all individuals who initiated combination antiretroviral therapy. We identified those individuals who experienced virologic failure (defined as a human immunodeficiency virus [HIV] RNA level >1000 copies/mL), received modified therapy, and subsequently had a second episode of virologic failure. Multivariate Cox regression was used to assess factors associated with time to second regimen failure and the time to death after the onset of second regimen failure.

Results

Of the 42,790 individuals who received therapy, 7159 experienced a second virologic failure. The risk of second virologic failure decreased from 1996 (56 cases per 100 person-years) through 2005 (16 cases per 100 person-years; P < .001). The cumulative mortality after onset of second virologic failure was 26% at 5 years and decreased over time. A history of AIDS, a lower CD4+ T cell count, and a higher plasma HIV RNA level were each independently associated with mortality. Similar trends were observed when analysis was limited to the subset of previously treatment-naive patients

Conclusions

Although the rates of multiple regimen failure have decreased dramatically over the past decade, mortality rates for those who have experienced failure of at least 2 regimens have remained high. Plasma HIV RNA levels, CD4+ T cell counts at time of treatment failure, and a history of AIDS remain independent risk factors for death, which emphasizes that these factors remain important targets for those in need of more-aggressive therapeutic interventions.

Background

The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain.

Methods

We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group).

Results

In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001).

Conclusions

The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.