Antiretroviral Therapy In Patients Research Articles

Antiretroviral considerations in HIV-infected patients undergoing bariatric surgery.

With the advent of antiretroviral therapy and the resultant decrease in mortality among adults living with human immunodeficiency virus (HIV), there is now an increased incidence of obesity and obesity-related comorbidities in these patients. Bariatric surgery is becoming an increasingly common treatment option for patients who are classified as clinically obese. There are limited data regarding the use of antiretroviral therapy in patients who have undergone bariatric surgery. The purpose of this review was to evaluate the available literature regarding antiretroviral therapy and pharmaceutical properties in this special population. Literature review was performed through PubMed, utilizing search terms of bariatric surgery, sleeve gastrectomy, Roux-en-Y, HIV infection, obesity and antiretroviral. Direct medical information requests to antiretroviral pharmaceutical manufacturers were also completed. Several case series and case reports have been published which demonstrate minimal risk of complications and maintenance of virologic suppression in the vast majority of patients. Bariatric surgery appears to be an effective mechanism for assistance in controlling obesity in patients infected with HIV; however, numerous factors may impact the safe and effective use of antiretroviral therapy. Due to the physiologic changes and postoperative management following bariatric surgery, evaluation of the patients' medication regimens must be considered and several factors should be taken into account when choosing the appropriate antiretroviral regimen for these patients. Furthermore, communication between the patients' surgeon, HIV provider and a clinical pharmacist should occur prior to surgery to ensure the patient is optimized to achieve the best outcome including maintaining virologic suppression.

Use of a Self-Report Medication Adherence Scale for Measuring Adherence to Antiretroviral Therapy in Patients With HIV/AIDS.

This study examined the psychometric properties of a 9-item Morisky Medication Adherence Scale (MMAS-9) adapted specifically for patients with HIV/AIDS. We used data from two randomized controlled trials investigating telephone-delivered interventions for improving adherence to antiretroviral therapy to assess reliability (Cronbach's α and Pearson's product correlation) and validity (convergent and concurrent) of the MMAS-9. The internal consistency (Cronbach's α) of the MMAS-9 was .66 (study 1) and .69 (study 2); 3-month test-retest reliability (Pearson's correlation) ranged from .50 to .74. Validity was supported by associations with electronic event monitored adherence, social support, depressive symptoms, self-efficacy, stigma, regimen complexity, and impact of side effects in the hypothesized direction. The adapted MMAS-9 demonstrated good convergent validity but somewhat lower internal consistency reliability than other reports.

Protocolo diagnóstico de la afectación hematológica importada

Haematological disorders are a very common occurrence in both travellers and immigrants. The most frequent disorders are eosinophilia, neutropaenia, anaemia and thrombocytopenia, whose diagnosis should be followed by a detailed and protocolised examination. Particularly among the immigrant population, it is crucial to first rule out an HIV infection, in which case the haematological alterations could be due to the infection itself, the adverse effects of the patient's antiretroviral therapy, certain immune conditions or other HIV-associated processes. Once an HIV infection has been ruled out, we should continue the diagnostic process by differentiating between travellers and immigrants, as the cause of these disorders differs between the two groups. Apart from an HIV infection, the presence of pancytopenia should generally lead to an initial diagnosis of either malaria or visceral leishmaniasis.

Renal effects of non-tenofovir antiretroviral therapy in patients living with HIV

A review of literature published regarding non-tenofovir antiretroviral agents causing renal adverse effects was conducted. The literature involving renal adverse effects and antiretroviral therapy is most robust with protease inhibitors, specifically atazanavir and indinavir, and includes reports of crystalluria, leukocyturia, nephritis, nephrolithiasis, nephropathy and urolithiasis. Several case reports describe potential nephropathy (including Fanconi syndrome) secondary to administration of abacavir, didanosine, lamivudine and stavudine. Case reports documented renal events such as acute renal failure, nephritis, proteinuria and renal stones with efavirenz administration. Regarding rilpivirine, a small increase of serum creatinine levels (SCr) was found in clinical trials; however, the clinical significance and impact on actual renal function is unknown. The integrase strand transfer inhibitors and enfuvirtide have a relatively safe renal profile, although studies have shown dolutegravir and raltegravir cause mild elevations in SCr without an impact on actual renal function. This is similar to the reaction observed with cobicistat, the pharmacokinetic enhancer frequently given with elvitegravir.

Prioritization of antiretroviral therapy in patients with high CD4 counts, and retention in care: lessons from the START and Temprano trials.

Initiation of antiretroviral therapy is not a once in a lifetime opportunity. In some resource constrained settings financial limitations make it necessary to prioritize treatment initiation for some groups of patients. In developed countries, there are patients who are reluctant to initiate treatment. Subgroup analysis of the START trial can inform recommendations for which patients with CD4 counts >500 cells mm3 temporary postponement of treatment initiation is safer. These include individuals aged <30 years and/or with CD4/CD8 ratio of >0.8 and/or viral load of <5000. This is because these individuals are at very low risk of disease progression in the subsequent 2 to 3 years, the risk is minimally diminished by antiretroviral therapy and is virtually identical in the first 18 months of therapy regardless of treatment initiation. In addition, asymptomatic young individuals are at higher risk of loss‐to‐follow and of low adherence to treatment, and those with low viral loads are less likely to transmit the virus. In addition, lessons from START and Temprano can help design trials to investigate strategies to decrease losses‐to‐follow‐up, while minimizing risks to patients.

Long-term Therapeutic Impact of the Timing of Antiretroviral Therapy in Patients Diagnosed With Primary Human Immunodeficiency Virus Type 1 Infection.

We aimed to determine the consequences of delayed human immunodeficiency virus type 1 (HIV-1) infection diagnosis by comparing long-term outcomes depending on the time of combination antiretroviral therapy (cART) initiation in patients diagnosed during primary HIV infection (PHI). We selected patients from the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) PRIMO cohort, treated for ≥36 months, with sustained HIV RNA <50 copies/mL: 77 treated within 1 month following PHI diagnosis (immediate ART) and 73 treated >12 months after infection (deferred ART). We measured inflammatory biomarkers from PHI through the last visit on cART, and CD4+ and CD8+ T-cell activation and plasma ultrasensitive HIV RNA at the last visit. Inflammation/activation levels were compared with those of uninfected controls. We modeled CD4+ count, CD4:CD8 ratio, and HIV DNA dynamics on cART. The decrease of HIV DNA levels was more marked in the immediate than deferred ART group, leading to a sustained mean difference of -0.6 log10 copies/106 peripheral blood mononuclear cells. Immediate ART led to improved CD4+ T-cell counts and CD4:CD8 ratios over the first 4 years of cART. At the last visit (median, 82 months), there was no difference between groups in CD4+ counts, CD4:CD8 ratio, ultrasensitive HIV RNA, or inflammation/activation marker levels. Long-term suppressive cART failed to normalize inflammation levels, which were not associated with immunovirological markers. Antiretroviral therapy initiated during PHI promotes long-term reduction of HIV reservoir size. In patients with sustained virologic suppression, inflammation may be driven by non-HIV-related factors.

Tuberculosis Meningitis.

As the most severe form of tuberculosis (TB), TB meningitis disproportionately affects developing countries and results in significant morbidity and mortality. In this report, we review recent updates in the epidemiology, diagnosis, and management of TB meningitis. Young children and people living with HIV continue to be at highest risk for TB meningitis. Early diagnosis remains challenging, especially since conventional diagnostic tests have sub-optimal sensitivity and specificity. Recently, nucleic acid amplification testing emerged as the preferred diagnostic modality due to its rapid turnaround time and high specificity. Several recent studies have assessed the optimal treatment for TB meningitis. While the benefit of treatment intensification, by increasing rifampin dosing or adding a fluoroquinolone, is unclear, a growing body of evidence suggests that steroids confer a survival advantage, particularly in patients with mild disease. Additionally, TB meningitis management is further complicated by high rates of HIV co-infection. Recent data suggest that unlike other forms of TB, early initiation of antiretroviral therapy in patients with TB meningitis is associated with higher rates of adverse reactions, without improved survival. TB meningitis continues to be a significant problem worldwide. Despite recent advances, more studies are warranted to improve early disease detection and optimize therapy.

Measuring and managing cognitive impairment in HIV

: Cognitive impairment remains a frequently reported complaint in HIV-positive patients despite virologically suppressive antiretroviral therapy. Rates of cognitive impairment in antiretroviral treated HIV-positive cohorts vary and strongly depend on definitions utilized.The underlying pathogenesis is likely to be multifactorial and includes immune activation, neuroinflammation, antiretroviral neurotoxicity, the presence of noninfectious comorbidities such as vascular disease and depression and patient lifestyle factors such as recreational drug use.Contributing factors to cognitive impairment may change over time with ageing HIV-positive populations. Cerebrovascular disease and neurodegenerative causes of cognitive impairment may become more common with advancing age; how these factors interact with HIV-associated cognitive impairment is not yet known.Cerebrospinal fluid HIV RNA escape may occur in up to 10% of patients undergoing lumbar puncture clinically and can be associated with compartmentalized and resistant virus.Changes in antiretroviral therapy in patients with cognitive impairment should be based on current and historic resistance profiles of cerebrospinal fluid and plasma virus, or on potential antiretroviral drug neurotoxicity. Whether and how antiretroviral therapy should be changed in the absence of these factors is not known and requires study in adequately powered randomized trials in carefully selected clinical cohorts.

Durability of viral suppression with first-line antiretroviral therapy in patients with HIV in the UK: an observational cohort study

SummaryBackgroundThe length of time that people with HIV on antiretroviral therapy (ART) with viral load suppression will be able to continue before developing viral rebound is unknown. We aimed to investigate the rate of first viral rebound in people that have achieved initial suppression with ART, to determine factors associated with viral rebound, and to use these estimates to predict long-term durability of viral suppression.MethodsThe UK Collaborative HIV Cohort (UK CHIC) Study is an ongoing multicentre cohort study that brings together in a standardised format data on people with HIV attending clinics around the UK. We included participants who started ART with three or more drugs and who had achieved viral suppression (≤50 copies per mL) by 9 months after the start of ART (baseline). Viral rebound was defined as the first single viral load of more than 200 copies per mL or treatment interruption (for ≥1 month). We investigated factors associated with viral rebound with Poisson regression. These results were used to calculate the rate of viral rebound according to several key factors, including age, calendar year at start of ART, and time since baseline.ResultsOf the 16 101 people included, 4519 had a first viral rebound over 58 038 person-years (7·8 per 100 person-years, 95% CI 7·6–8·0). Of the 4519 viral rebounds, 3105 (69%) were defined by measurement of a single viral load of more than 200 copies per mL, and 1414 (31%) by a documented treatment interruption. The rate of first viral rebound declined substantially over time until 7 years from baseline. The other factors associated with viral rebound were current age at follow-up and calendar year at ART initiation (p<0·0001) and HIV risk group (p<0·0001); higher pre-ART CD4 count (p=0·0008) and pre-ART viral load (p=0·0003) were associated with viral rebound in the multivariate analysis only. For 1322 (29%) of the 3105 people with observed viral rebound, the next viral load value after rebound was 50 copies per mL or less with no regimen change. For HIV-positive men who have sex with men, our estimates suggest that the probability of first viral rebound reaches a plateau of 1·4% per year after 45 years of age, and 1·0% when accounting for the fact that 29% of viral rebounds are temporary elevations.InterpretationA substantial proportion of people on ART will not have viral rebound over their lifetime, which has implications for people with HIV and the planning of future drug development.FundingUK Medical Research Council.

Total cellular HIV-1 DNA decreases after switching to raltegravir-based regimens in patients with suppressed HIV-1 RNA

BackgroundThe integrase inhibitor raltegravir has been used to intensify antiretroviral therapy in patients with undetectable plasma HIV-1RNA, resulting in variable perturbation of HIV-1 nucleic acids levels in peripheral blood. ObjectivesWe aimed at monitoring residual plasma HIV-1RNA and total cellular HIV-1DNA in virologically suppressed patients switching to raltegravir-based regimens. Study designFifty-eight subjects on protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens, with plasma HIV-1RNA levels <40 copies/ml for ≥6 months and CD4 counts >200cells/μl for ≥12 months were enrolled. Thirty-four patients were from the treatment simplification RASTA randomized study switching standard therapy to a raltegravir-based regimen (RASTA group), while 24 continued a PI or NNRTI based-regimen (controls). Residual plasma HIV-1RNA (5-40copies/mL) and HIV-1DNA were assessed at 0, 24 and 48 weeks. ResultsAt week 0 (W0), HIV-1DNA was detected in all patients while at W48 it was detectable in 82.4% of the RASTA group vs 100% of controls (p=0.03). There was a significant decline of HIV-1DNA at W48 in the RASTA group (mean change from baseline −0.21 [95% CI −0.41; −0.01] log10 copies/106 CD4; p=0.03) but not in controls. Ultrasensitive HIV-1RNA was detectable at baseline in 50% of RASTA group vs 67% of controls and at W48 in 32.4% vs 42%, respectively. No differences were found between HIV-1RNA levels at baseline and W48 within and between groups. ConclusionsSwitching successful therapy to raltegravir-based regimens may be associated with a decrease of the HIV-1 reservoir, as measured by peripheral blood cellular HIV-1DNA levels.

Association of knowledge on ART line of treatment, scarcity of treatment options and adherence.

BackgroundAdherence to Antiretroviral Therapy (ART) is critical piece in the management of HIV infected patients. Despite the benefits of ART, non-adherence to ART persists. This study explores association between patient’s knowledge of the ART line of treatment, availability of future treatment options and adherence.MethodsA cross sectional survey of HIV infected adolescent and adults was conducted. Cumulative optimal and sub-optimal adherence was defined as percentage adherence of ≥ 95 % and < 95 %, respectively. Binomial regression models were used to assess the association of patient’s knowledge of the ART line of treatment, availability of future treatment options and adherence.ResultsOf the 402 patients reviewed, 101 (25.1 %) patients knew their ART line of treatment and were aware that future treatment options are limited. Compared to those who were not aware of the ART line of treatment and/or scarcity of future treatment options, those who were aware were more likely to be adherent (adjusted prevalence ratio [APR], 1.1; 95 % CI, 1.0–1.3).ConclusionThe study reports knowledge of patient’s ART line of treatment and future treatment options is important indicator of adherence to ART. Although majority of the patients did not have the knowledge, those who had the knowledge demonstrated to be more adherent. It is critical for the physicians/health care providers in these settings to clearly educate patients about ART line of treatment and limited availability of future treatment options as such information is likely to influence individual behavior and improve patient’s adherence to ART.

Protective efficiency of “Phosphogliv” at high active antiretroviral therapy in patients with HIV-infection, associated with chronic viral hepatitis C

Protective efficiency of “Phosphogliv” at high active antiretroviral therapy in patients with HIV-infection, associated with chronic viral hepatitis C

HIV INFECTION STAGE, ANTIRETROVIRAL THERAPY SCHEME AND PATIENT IMMUNE STATUS INFLUENCE ON HIV/TB CO-INFECTION OUTCOME

Retrospective research of 381 clinical records is conducted to study HIV infection influence on stationary stage of tuberculosis treatment outcome in HIV-TB co-infected patients. All cases were divided depending on a hospitalization outcome on favorable and adverse. At most of patients tuberculosis of respiratory organs met. Immunological researches were conducted, the stage of HIV infection was registered and the issue of purpose of anti-retroviral therapy was resolved. Besides, as indirect signs of an immunodeficiency at the patients with a combination of tuberculosis and HIV infection who were on hospitalization the indicators received when carrying out clinical laboratory trials were analyzed: absolute and relative quantity of lymphocytes according to the general blood test, the contents the globulin fractions and circulating immune complexes concentration according to the clinical chemistry blood test. At an assessment of results in both groups of research more than at a half of patients existence of HIV infection at late stages that speaks about late identification and neglect of an immunodeficiency was revealed. At patients with tuberculosis of lungs in combination with HIV infection at a failure statistically significant decrease in an immunoregulatory index is revealed. It is interesting that the level of CD4 lymphocytes and a stage of HIV infection had no impact on the co-infection’s outcome. However, existence of virus loa ding more than 100 000 copies/ml reduced probability favorable an outcome of treatment of tuberculosis at the patient with HIV infection. Timely purpose of anti-retroviral therapy at patients with co-infection increased chances of treatment of tuberculosis at patients with an immunodeficiency. Frequency of adverse side effect of antiviral therapy met equally often at patients in both groups. Thus, patients at any stages of HIV infection with any forms of tuberculosis, including generalized, had a chance to have a favorable outcome of a disease. We consider the reasonable recommendation about carrying out anti-retroviral therapy of patients by all with a combination of tuberculosis and HIV infection, irrespective of the HIV infection stage.

Clinical and Pharmacoeconomic Results of the Usage of Various HIV Reverse Transcriptase Inhibitors in the Schemes of Antiretroviral Therapy of Patients Receiving Therapy for the Chronic Hepatitis C Virus

Efficacy, safety, and economical aspects of treatment with abacavir, zidovudine, stavudine, and phosphazide in the schemes of antiretroviral therapy of the HIV-infected patients receiving therapy for hepatitis C virus were tested. Clinical, immunological, and virologic efficacy of treatment and dynamics of hemoglobin, thrombocytes, and alanine aminotransferase as markers of common adverse events recorded at the start of the antiviral therapy of chronic hepatitis C and after 4, 8, 12, 24, 48 weeks of the treatment were evaluated. The usage of these drugs in the schemes of antiretroviral therapy exhibited efficacy, high tolerability and safety for all HIV reverse transcriptase inhibitors.

Strategy for the assessment of compliance with antiretroviral therapy in patients with HIV infection

The study was aimed at identifying prognostic factors of antiretroviral therapy (ARVT) in patients with HIV infection at different stages of the disease and developing an algorithm for the three-component assessment of compliance with therapy. A total of 280 patients given ARVT for at least 6 months were available for comprehensive examination, questionnaire study for the detection of non-compliance risk factors, and psychological testing with the evaluation of non-compliance from the anxiety level (Sheehan scale) with the use of cluster analysis. The study revealed the most significant criteria for the assessment of compliance with therapy and non-compliance risk factors associated with ARVT conditions.

Clinical and Epidemiological Differences between Women and Men with HIV Infection in Mexico

Objective: To evaluate the differences in gender for epidemiological, immunological, and virological outcomes at baseline, and response after 24 weeks of antiretroviral therapy in patients treated at the Hospital de Infectologia “La Raza” National Medical Center. Methods: We reviewed the medical records from March to August 2014 of outpatients who started treatment in our clinic; 65 women and 138 men in a cross-sectional study. Descriptive results are summarized using the median and 25th-75th interquartile range (IQR). Baseline differences were tested using Fisher’s exact test and the Chi-squared test. Analyses of continuous variables were performed using the Mann-Whitney U test. Results: Similar proportions of women and men were found in the following factors: living in metropolitan area, age 100,000 copies/mL (37% vs. 54%, p=0.020); and women with virological treatment failure (10.8% vs. 2.2%, p=0.008). Conclusion: Compared with men, mostly women showed adverse epidemiological and clinical conditions that made women more vulnerable to transmission through heterosexual activity, and more frequently present virological failure.

Metabolic and cardiovascular effects of combined antiretroviral therapy in patients with HIV infection. Systematic review of literature

In HIV infected patients an increased incidence of cardiac events has been reported since the introduction of highly active antiretroviral therapy (HAART). Antiretroviral drugs' regimens are, in fact, associated with several metabolic side effects, such as dyslipidemia, impaired glucose metabolism and abnormal body fat distribution, that increase cardiovascular risk of HIV subjects. In addition, HIV infection itself, the chronic inflammatory status and the frequent presence in this population of traditional risk factors contribute to an higher incidence of cardio and cerebrovascular events. In last years several studies showed the occurrence of carotid vascular impairment in patients treated with protease inhibitors (PI). Similarly the DAD Study reported an increase of 26% of the risk of myocardial infarction in patients on HAART and that this risk was independently associated with longer exposure to PI, after multivariate adjustments. A correct evaluation of the metabolic status before starting HAART and an adequate control of drugs-related metabolic abnormalities may reduce the incidence of cardiac events and still improve HIV patients prognosis. This review will focus on the metabolic effects of antiretroviral drugs and on the contribution of combination antiretroviral therapy on cardiovascular risk.

Carotid artery thickness is associated with chronic use of highly active antiretroviral therapy in patients infected with human immunodeficiency virus: A 3.0 Tesla magnetic resonance imaging study.

While patients with HIV infection have an elevated stroke risk, ultrasound studies of carotid artery wall thickness have reported variable results. We hypothesized that subjects with HIV infection on chronic highly active antiretroviral therapy (HAART) would have increased carotid artery wall thickness by magnetic resonance imaging (MRI). This cross-sectional study compared carotid artery wall thickness between 26 individuals infected with HIV on chronic HAART and 20 controls, without HIV infection but with similar cardiovascular risk factors, using 3.0-T noncontrast MRI. Inclusion criteria included male gender, age 35-55 years, and chronic HAART (≥ 3 years) among HIV-seropositive subjects; those with known cardiovascular disease or diabetes were excluded. Between subjects with HIV infection and controls, there were no differences in mean (±SD) age (47.8 ± 5.0 vs. 47.8 ± 4.7 years, respectively; P = 0.19) or cardiovascular risk factors (P > 0.05 for each). Mean (±SD) wall thickness was increased in those with HIV infection vs. controls for the left (0.88 ± 0.08 vs. 0.83 ± 0.08 mm, respectively; P = 0.03) and right (0.90 ± 0.10 vs. 0.85 ± 0.07 mm, respectively; P = 0.046) common carotid arteries. Among individuals with HIV infection, variables associated with increased mean carotid artery wall thickness included lipoaccumulation [+0.09 mm; 95% confidence interval (CI) 0.03-0.14 mm; P = 0.003], Framingham risk score ≥ 5% (+0.07 mm; 95% CI 0.01-0.12; P = 0.02 mm), and increased duration of protease inhibitor therapy (+0.03 mm per 5 years; 95% CI 0.01-0.06 mm; P = 0.02). Individuals with HIV infection on chronic HAART had increased carotid artery wall thickness as compared to similar controls. In subjects with HIV infection, the presence of lipoaccumulation and longer duration of protease inhibitor therapy were associated with greater wall thickness.

Outcomes of pharmacist-assisted management of antiretroviral therapy in patients with HIV infection: A risk-adjusted analysis.

The impact of pharmacist-assisted management (PAM) of pharmacotherapy for patients with human immunodeficiency virus (HIV) infection was investigated. A retrospective cohort analysis was conducted to evaluate antiretroviral therapy (ART) outcomes in treatment-naive patients initiated on ART at an HIV clinic. Eligible patients enrolled in the clinic during the period 1999-2013 were classified into two groups: those referred to a clinic-based HIV pharmacist for initiation of ART (the PAM group) and those managed by a primary care provider (the control group). The primary study objective was the median time to viral suppression; secondary objectives included the durability of response to the first ART regimen. Relative hazards for the events of interest were estimated using a marginal structural Cox proportional hazards model and Kaplan-Meier curves, with inverse probability weights used to control for selection and confounding bias. Patients referred for PAM services (n = 819) typically had higher baseline viral loads and lower CD4+ cell counts than those in the control group (n = 436). The likelihood of viral suppression during the first two years after ART initiation was significantly higher in the PAM group versus the control group (hazard ratio, 1.37; 95% confidence interval, 1.18-1.59; p < 0.0001). The median durability of the first ART regimen was 100 months in the PAM group versus 44 months in the control group (p > 0.05). In treatment-naive patients, suppression of HIV viral load occurred earlier when pharmacists assisted with initiating ART than when ART was initiated without that assistance.

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

BackgroundData from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.MethodsWe randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non–AIDS-related event, or death from any cause.ResultsA total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non–AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions.ConclusionsThe initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.)