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To assess the influence of hepatitis C virus (HCV) on the natural history of human immunodeficiency virus (HIV) infection, a longitudinal study was conducted among 416 HIV-positive, AIDS-free persons infected through injecting drug use or homosexual or heterosexual activity and with known seroconversion dates. End points were diagnosis of AIDS and a CD4 cell count of < 100 x 10(6) cells/L. HCV antibodies were detected in 214 persons (51.4%). The crude relative hazard (RH) of progression to AIDS was 0.96 (95% confidence interval [CI], 0.53-1.76) for HCV-coinfected participants compared with those not coinfected. After adjustment for CD4 cell count, the RH was 0.97 (95% CI, 0.52-1.79). Similar RHs were found using a CD4 cell count of < 100 x 10(6) cells/L as the end point. The median CD4 cell loss was 4.83 x 10(6) cells/L per month among coinfected persons and 5.70 x 10(6) cells/L per month among the others. These results suggest that coinfection with HCV does not influence clinical and immunologic progression of HIV disease. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the risk of COVID-19-related hospitalization and death (CovH/D), among high-risk individuals early treated for COVID-19 and to identify associated factors., Methods and Results: A multicenter cohort of 12,475 high-risk outpatients (female 50.2%, median age 70 years [IQR 57-80], fully vaccinated 79.1%, immunocompromised 23.2%) treated with monoclonal antibodies or antivirals for mild-to-moderate COVID-19 (March 2021-May 2023) in the Lazio region, Italy. The unadjusted risk of CovH/D by Day 30 was 3.08% (95% CI 2.7%-3.4%). By means of logistic regression models, which included a specific set of potential confounders for each exposure of interest, we observed a higher risk for the elderly, unvaccinated and immunocompromised participants. Using the "Delta period" as a reference, a decreased risk was observed for Omicron waves., Conclusions: Despite the administration of COVID-19 early treatment and the decreasing risk of CovH/D across the calendar periods, the elderly, the unvaccinated and the immunocompromised people remain at high risk of clinical progression., (© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

We estimated the dynamics of the neutralizing response against XBB sublineages and T cell response in persons with HIV (PWH) with previous AIDS and/or CD4 < 200/mm 3 receiving the bivalent original strain/BA.4-5 booster dose in fall 2022. Samples were collected before the shot (Day 0), 15 days, 3, and 6 months after. PWH were stratified by immunization status: hybrid immunity (HI; vaccination plus COVID-19) versus nonhybrid immunity (nHI; vaccination only). Fifteen days after the booster, 16% and 30% of PWH were nonresponders in terms of anti-XBB.1.16 or anti-EG.5.1 nAbs, respectively. Three months after, a significant waning of anti-XBB.1.16, EG.5.1 and -XBB.1 nAbs was observed both in HI and nHI but nAbs in HI were higher than in nHI. Six months after both HI and nHI individuals displayed low mean levels of anti-XBB.1.16 and EG.5.1 nAbs. Regarding T cell response, IFN-γ values were stable over time and similar in HI and nHI. Our data showed that in PWH, during the prevalent circulation of the XBB.1.16, EG.5.1, and other XBB sublineages, a mRNA bivalent vaccine might not confer broad protection against them. With a view to the 2023/2024 vaccination campaign, the use of the monovalent XBB.1.5 mRNA vaccine should be urgently warranted in PWH to provide adequate protection., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Pre-exposure vaccination with MVA-BN has been widely used against mpox to contain the 2022 outbreak. Many countries have defined prioritized strategies, administering a single dose to those historically vaccinated for smallpox, to achieve quickly adequate coverage in front of low supplies. Using epidemiological models, real-life effectiveness was estimated at approximately 36%-86%, but no clinical trials were performed. Few data on MVA-BN immunogenicity are currently available, and there are no established correlates of protection. Immunological response in PLWH in the context of the 2022 outbreak was also poorly described., Methods: Blood samples were collected from participants eligible for pre-exposure MVA-BN vaccination before (T1) receiving a full course of vaccine (single-dose for vaccine-experienced or smallpox-primed and two-dose for smallpox vaccine-naïve or smallpox non-primed) and one month after the last dose (T2 and T3, respectively). MPXV-specific IgGs were measured by in-house immunofluorescence assay, using 1:20 as screening dilution, MPXV-specific nAbs by 50% plaque reduction neutralization test (PRNT 50 , starting dilution 1:10), and IFN-γ-producing specific T cells to MVA-BN vaccine, by ELISpot assay. Paired or unpaired t-test and Wilcoxon or Mann-Whitney test were used to analyse IgG and nAbs, and T-cell response, as appropriate. The probability of IgG and nAb response in vaccine-experienced vs. vaccine-naïve was estimated in participants not reactive at T1. The McNemar test was used to evaluate vaccination's effect on humoral response both overall and by smallpox vaccination history. In participants who were not reactive at T1, the proportion of becoming responders one month after full-cycle completion by exposure groups was compared by logistic regression and then analysed by HIV status strata (interaction test). The response was also examined in continuous, and the Average Treatment Effect (ATE) of the difference from baseline to schedule completion according to previous smallpox vaccination was estimated after weighting for HIV using a linear regression model. Self-reports of adverse effects following immunization (AEFIs) were prospectively collected after the first MVA-BN dose (T1). Systemic (S-AEFIs: fatigue, myalgia, headache, GI effects, chills) and local (L-AEFIs: redness, swelling, pain) AEFIs were graded as absent (grade 0), mild (1), moderate (2), or severe (3). The maximum level of severity for S-AEFIs and L-AEFIs ever experienced over the 30 days post-dose by vaccination exposure groups were analysed using a univariable multinomial logistic regression model and after adjusting for HIV status; for each of the symptoms, we also compared the mean duration by exposure group using an unpaired t-test., Findings: Among the 164 participants included, 90 (54.8%) were smallpox vaccine-experienced. Median age was 49 years (IQR 41-55). Among the 76 (46%) PLWH, 76% had a CD4 count >500 cells/μL. There was evidence that both the IgG and nAbs titers increased after administration of the MVA-BN vaccine. However, there was no evidence for a difference in the potential mean change in humoral response from baseline to the completion of a full cycle when comparing primed vs. non-primed participants. Similarly, there was no evidence for a difference in the seroconversion rate after full cycle vaccination in the subset of participants not reactive for nAbs at T1 (p = 1.00 by Fisher's exact test). In this same analysis and for the nAbs outcome, there was some evidence of negative effect modification by HIV (interaction p-value = 0.17) as primed people living with HIV (PLWH) showed a lower probability of seroconversion vs. non-primed, and the opposite was seen in PLWoH. When evaluating the response in continuous, we observed an increase in T-cell response after MVA-BN vaccination in both primed and non-primed. There was evidence for a larger increase when using the 2-dose vs. one-dose strategy with a mean difference of -2.01 log 2 (p ≤ 0.0001), after controlling for HIV. No evidence for a difference in the risk of developing any AEFIs of any grade were observed by exposure group, except for the lower risk of grade 2 (moderate) fatigue, induration and local pain which was lower in primed vs. non-primed [OR 0.26 (0.08-0.92), p = 0.037; OR 0.30 (0.10-0.88), p = 0.029 and OR 0.19 (0.05-0.73), p = 0.015, respectively]. No evidence for a difference in symptom duration was also detected between the groups., Interpretation: The evaluation of the humoral and cellular response one month after the completion of the vaccination cycle suggested that MVA-BN is immunogenic and that the administration of a two-dose schedule is preferable regardless of the previous smallpox vaccination history, especially in PLWH, to maximize nAbs response. MVA-BN was safe as well tolerated, with grade 2 reactogenicity higher after the first administration in vaccine-naïve than in vaccine-experienced individuals, but with no evidence for a difference in the duration of these adverse effects. Further studies are needed to evaluate the long-term duration of immunity and to establish specific correlates of protection., Funding: The study was supported by the National Institute for Infectious Disease Lazzaro Spallanzani IRCCS "Advanced grant 5 × 1000, 2021" and by the Italian Ministry of Health " Ricerca Corrente Linea 2 "., Competing Interests: The authors declare that no conflicting financial interests or other competing relationships exist., (© 2023 The Author(s).)

Objectives: To investigate immunogenicity of SARS-CoV-2 vaccine third booster dose (3BD; fifth dose) with bivalent vaccine original/BA4/5 vaccine in people living with HIV (PLWH)., Methods: This is an observational cohort study to evaluate the outcomes of SARS-CoV-2 vaccination (HIV-VAC study). We analyzed microneutralization assay and interferon-γ production in 48 PLWH on antiretroviral therapy with clusters of differentiation (CD4) count <200 cell/mm 3 and/or previous AIDS according to immunization status: vaccinated PLWH who had a previous SARS-CoV-2 infection (hybrid immunization, HI) vs those only vaccinated (non-hybrid immunization, nHI) and current CD4 count., Results: After 15 days from its administration (T1), the 3BD bivalent messenger RNA vaccine elicited a statistically significant increase of neutralizing antibodies (nAbs) geometric mean titers from T0 to T1 against W-D614G (fold increase 4.8; P <0.0001), BA.5 (8.6 P <0.0001), BQ.1.1 (6.4, P <0.0001) and XBB.1 (6.5, P <0.0001). When compared to BA.5, nAbs geometric mean titers against BQ.1.1 and XBB.1 decreased by 3.5 and 4.1-fold, respectively. After controlling for age, years from AIDS diagnosis, CD4 count at administration and CD4 count nadir, the fold change reduction in nAbs response to other variants of concerns as compared to BA.1, was larger in participants with HI vs those nHI: 0.59 lower (95% confidence interval 0.36-0.97, P = 0.04) for BQ.1.1 and 0.67 lower (95% confidence interval: 0.47-0.96, P = 0.03) for XBB.1. In contrast, the analysis carried little evidence for an association between current CD4 count and response to the fifth dose of bivalent vaccine. Furthermore, cell-mediated immunity remained stable., Conclusion: Our data support the current recommendation of offering bivalent mRNA vaccine booster doses to PLWH with low CD4 count or previous AIDS at first vaccination, especially in those who never previously acquired SARS-CoV-2 and regardless of current CD4 count., Competing Interests: Declarations of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The Watson-Jones interval plane between tensor fascia lata (TFL) and the gluteus medius (GM) has come back into fashion in the past few years - Röttinger described the anterolateral minimal invasive approach (ALMI) for use in total hip replacement, in which the standard Watson-Jones interval was used, but with a completely intermuscular plane. However, the term anterolateral is often still utilised to describe intramuscular approaches in which the GM was violated, thus creating a potential misunderstanding in the literature. Accordingly, we have designed a study to answer the following questions: (1) are there articles in the recent literature that use the term "anterolateral" to describe different approaches; (2) which would be the correct description of the anterolateral approach?, Methods: We did a systematic review of the literature based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, to look for peer reviewed papers of any evidence level focusing on the definition of anterolateral approach; MEDLINE and EMBASE were searched., Results: 73 manuscripts met the criteria of the systematic search. 53 papers (72.6%) reported the term anterolateral approach to describe a complete intermuscular approach between the interval between GM and TFL. Nonetheless, in the remaining 20 papers (27.4%) the term anterolateral was used to describe intramuscular approaches in which the gluteus medius was violated., Conclusion: In about 1 out of 4 papers in the recent literature, the term anterolateral was utilised to describe approaches that are completely different both in terms of anatomy and function.

The aim of this study is to investigate five hypothesized mechanisms of causation between depression and condomless sex with ≥ 2 partners (CLS2+) among gay, bisexual, and other men who have sex with men (GBMSM), involving alternative roles of self-efficacy for sexual safety and recreational drug use. Data were from the AURAH cross-sectional study of 1340 GBMSM attending genitourinary medicine clinics in England (2013-2014). Structural equation modelling (SEM) was used to investigate which conceptual model was more consistent with the data. Twelve percent of men reported depression (PHQ-9 ≥ 10) and 32% reported CLS2+ in the past 3 months. AURAH data were more consistent with the model in which depression was considered to lead to CLS2+ indirectly via low self-efficacy for sexual safety (indirect Beta = 0.158; p < 0.001) as well as indirectly via higher levels of recreational drug use (indirect Beta = 0.158; p < 0.001). SEM assists in understanding the relationship between depression and CLS among GBMSM.

Background: Polyethylene (PE) wear is a major contributor to implant loosening following total knee arthroplasty (TKA), and advanced bearings in TKA are being investigated with hopes of reducing or eliminate wear-related loosening. Currently, information on knee tribology is available from national joint registries and may be the best tools to evaluate the efficacy and safety of design innovations in joint arthroplasty., Questions/purposes: We performed a review of national joint registries trying to answer the following questions: "Which is the main factor directly related to revisions rate in TKA?" and "Are there new bearing options better than conventional ones?", Methods: A review was performed of all published annual reports of National Joint Registers, as well as of the literature. The search was carried out using and comparing the National Joint Registers., Results: Current data from registries for total knee arthroplasty indicates that age is the major factor affecting the outcome of primary total knee replacement. The 10-year cumulative revision rate for non-cross-linked PE was 5.8% and for XLPE it was 3.5%. The effect of cross-linked polyethylene was more evident in the younger patients. The survival of the oxidized zirconium (OxZr) femoral component appears better when compared to a similar age group of patients with conventional group of prostheses. Our review suggests that the revision rates are half for the OxZr components compared to conventional CoCr femoral components., Conclusions: Age is the most relevant single factor related to revision rate. Cross-linked PE has a statistical lower revision rate at 10 years compared to conventional PE and, in the OxZr group, the revision rate is 2 times lower than Co-Cr in the same group of age., Competing Interests: Fabrizio Matassi, MD, Christian Carulli, MD, Luigi Sirleo, MD, and Andrea Cozzi Lepri, MD, have declared that they have no conflict of interest. Roberto Civinini, MD, reports personal fees from Smith & Nephew, outside the work. Innocenti, MD, reports personal fees from Smith & Nephew, outside the work. Human/Animal Rights This article does not contain any studies with human or animal subjects performed by the any of the authors. Informed Consent N/A Required Author Forms Disclosure forms provided by the authors are available with the online version of this article.

Background: Oxidized zirconium (OxZr) femoral component for total knee arthroplasty (TKA) have been introduced in an attempt to reduce polyethylene wear and secondary osteolysis and improve longevity of implants., Questions/purposes: We reviewed clinical studies in literature evaluating OxZr femoral component for TKA. The aim of this review was to evaluate the clinical outcome and survival rate of TKA with an OxZr femoral component., Methods: A review of the existing literature was undertaken to collect data on the OxZr femoral component in order to provide a better understanding of its performance. Of 34 studies published in the literature, 8 met the eligibility criteria and were included in the final analysis., Results: Findings indicated that the mean Knee Society knee score improved in all series from preoperative to postoperative evaluation. The postoperative Knee Society knee score reported range from 84 to 95 and mean postoperative Knee Society functional score range from 74 to 90. The revision rate with this implant is low with up to 12.6 years of follow-up, with three revisions in total. The survival rate ranged from 100-98.7% at 5-7 years to 97.8% at 10 years., Conclusions: Excellent clinical outcome and high survival rate has been demonstrated for OxZr femoral component in TKA. No adverse reaction has been described for this new material., Competing Interests: Fabrizio Matassi, MD, Christian Carulli MD, Luigi Sirleo, MD, and Andrea Cozzi Lepri, MD have declared that they have no conflict of interest. Roberto Civinini, MD, reports personal fees from Smith & Nephew, outside the work. Innocenti, MD, reports personal fees from Smith & Nephew, outside the work. Human/Animal Rights This article does not contain any studies with human or animal subjects performed by the any of the authors. Informed Consent N/A Required Author Forms Disclosure forms provided by the authors are available with the online version of this article.

Dynamics of human immunodeficiency virus type 1 (HIV-1) tropism after antiretroviral therapy (ART) initiation and their association with disease progression are poorly investigated.This was a cohort study on subjects from the ICONA cohort receiving ART with persistently detectable (PD) or persistently undetectable (PU) viral load (VL) and with stored plasma or peripheral blood mononuclear cell (PBMC) samples at 2 time-points (T1, T2) after ART initiation. HIV-1 co-receptor tropism was determined by V3-loop sequencing and the geno2pheno algorithm. A switch in viral tropism was defined if the tropism classification at T2 differed from that observed at T1. Time to disease progression, defined as the occurrence of a new acquired immune deficiency syndrome (AIDS)-defining event/death from T2, was also evaluated.One hundred ninety-five patients were analyzed (124 PD, 71 PU). Over a median follow-up of 22.6 (19.8-28.1) months, PD and PU patients showed similar rates (95% confidence interval) of switch to a non-R5 virus [PD: 6.9 (3.7-11.2)/100-person-years of follow-up (PYFU); PU: 8.0 (3.4-14.5)/100-PYFU; P = 0.63] and of switch to a R5 virus [PD: 15.4 (7.3-26.4)/100-PYFU; PU: 8.1 (2.5-16.7)/100-PYFU; P = 0.38]. Switch to non-R5 virus was predicted by nadir CD4+ before T1.Twenty-two (18%) PD and 4 (6%) PU subjects experienced disease progression (P = 0.02). The risk of disease progression was independently associated with a switch in co-receptor tropism (adjusted hazard ratio = 4.06, 95% CI: 1.20-13.80, P = 0.03) as well as age, AIDS diagnosis, nadir CD4+ before T2, current CD4+, and VL.Switch of HIV-1 tropism under ART occurs in both directions, with similar rates in subjects with PD or PU VL and it might be predictive of future unfavorable clinical outcome.

Introduction: Recent acquisitions of the complex mechanisms of osseointegration between implants and host bone have gained attention, accordingly to the methods of evaluation of these interactions. DEXA analysis is considered an useful tool to assess such phenomena, in order to analyse in a quantitative manner the local metabolic activity of the bone, and to evaluate over the time the integration between host bone and prosthetic components. The purpose of the present study is to report about a preliminary experience in the analysis of osseointegration processes of patients undergoing a primary Total Hip Arthroplasty (THA) or a revision Total Knee Arthroplasty (rTKA)., Materials and Methods: Thirty patients undergoing THA and nineteen undergoing rTKA were included in this study. In fifteen cases of THA a standard cementless stem was used; in the other fifteen a short cementless stem was chosen. In all cases a cementless cup was implanted. In all patients undergoing rTKA, all implants had pressfit femoral and tibial diaphyseal stems; only the femoral component and the tibial plateau were cemented. DEXA evaluation was performed preoperatively, and at 3, 6, 12, and 24 months postoperatively for rTKA, and at 6 and 12 months for THA., Results: DEXA in THA showed a significant decrease at the femoral ROIs 1 and 7, and an increase in ROI 4. In rTKA a reduction of femoral BMD in R1, R7, and R4 was found, with maximum values of -13.6% in R1 and -11.89% in R7 at 24 months and a value of -2.55% in R4 at 12 months. On the tibial side, an increase in BMD R4 (with values of 2.18% still at 24 months), and a reduction in R7 (progressively lesser over the time) and in R1 (progressively higher) were found., Conclusions: After a joint replacement a full adhesion of the prosthetic surface to the host bone should be achieved through a local biological process named osseointegration. In some cases this process may not fully realize, so the secondary stability of the implant may fail. DXA is a valuable tool to follow over time the bone remodelling at the bone-prosthesis counterface in THA and in rTKA, in order to early detect any alterations of such phenomenon.

Introduction: Sexually transmitted diseases (STDs) data collected in HIV+ patients could be used as indicator of risky sexual behaviour possibly linked to HIV transmission. We described the STDs incidence over time and identified higher incidence factors., Methodology: All patients in the ICONA Foundation Study enrolled after 1998 were included. STDs considered: any-stage syphilis, human papilloma virus (HPV) diseases, gonococcal and non-gonococcal urethritis, herpes simplex virus (HSV) genital ulcers, vaginitis and acute hepatitis B virus (HBV), hepatitis A virus (HAV), and hepatitis C virus (HCV) infections (only for non-IVDU (intravenous drug user) patients). STDs incidence rate (IR): number of STDs divided by person years of follow-up (PYFU). Calendar periods: 1998-2002, 2003-2007 and 2008-2012. Predictors of STDs occurrence were identified using Poisson regression and sandwich estimates for the standard errors were used for multiple STD events., Results: Data of 9,168 patients were analyzed (median age 37.3 (SD=9.3), 74% male, 30% MSM). Over 46,736 PYFU, 996 episodes of STDs were observed (crude IR 17.3/1,000 PYFU). Median (IQR) CD4/mmc and HIV-RNA/mL at STD: 433 (251-600) and 10,900 (200-63,000). Highest crude IRs were observed for any-stage syphilis (3.95, 95% CI 3.59-4.35), HPV diseases (1.96, 1.71-2.24) and acute hepatitis (1.72, 1.49-1.99). At multivariable analysis (variables of adjustment shown in Figure 1), age (IRR 0.82 per 10 years younger, 95% CI 0.77-0.89), MSM contacts (IRR 3.03, 95% CI 2.52-3.64 vs heterosexual) and calendar period (IRR 1.67, 95% CI 1.42-1.96, comparing 2008-2012 with 1998-2002) significantly increased the risk of acquiring STDs. Moreover, having a HIV-RNA >50 c/mL (IRR 1.44, 95% CI 1.19-1.74 vs HIV-RNA <50 c/mL) and current CD4+ cell count <100/mmc (IRR 4.66, 95% CI 3.69-5.89, p<0.001 vs CD4+ cell count >500) showed an increased risk of STDs. Being on ARV treatment significantly reduced the risk of developing an STD (IRR 0.37, 95% CI 0.32-0.43) compared to ART-naïve people, even in the situation of temporary interruption of treatment (IRR 0.51, 95% CI 0.39-0.43) (see Figure 1)., Conclusions: The overall incidence of STDs has been increasing in the recent years. Interventions to prevent STDs and potential further spread of HIV infection should target the recently HIV diagnosed, the young population and MSM. Being on ARV treatment (potentially an indicator of whether a person is regularly seen for care) seems to reduce the risk of acquiring STDs independently of its viro-immunological effect.

Introduction: Serious non-AIDS events (SNAE) are frequent in HIV patients receiving cART. Current CD4 count was shown to be more strongly associated with infective compared to not-infective SNAE and unable to predict cardiovascular events. We investigated the relationship between baseline and current CD4 count and the risk of both infective and non-infective SNAE in HIV-positive patients according to current ART use., Methods: We included all HIV-positive persons enrolled in the ICONA Foundation Study cohort who had at least one follow-up visit. SNAE were grouped in infective (pneumonia, sepsis, endocarditis and meningitis) and non-infective (malignancies, chronic kidney disease, cardiovascular events, hepatic events and pancreatitis) aetiology. Incidence of these event groups were calculated overall and according to baseline and current CD4 count (grouped as 0-200, 201-350, 351-500, 501-750, and >750 cells/mm(3)). Participants' follow-up accrued from the date of enrolment (baseline) to a diagnosis of SNAE or their last visit. An event was defined the first time one of the considered SNAE occurred so that each person contributed a single event. A Poisson regression model for each of the two endpoints was used., Results: A total of 10,822 patients were included (25.3% females, 38.2% heterosexuals) and 26.6% had hepatitis co-infections. Median age was 36 (IQR 31-42) years. Overall, 423 not-infective and 385 infective SNAE were included. The most frequent non-infective SNAE were malignancies (n=202) and the most frequent infective SNAE were pneumonia (n=289). Crude rates of non-infective SNAE were 0.78, 1.08 and 0.80/100 PYFU, and those of infective SNAE were 1.00, 0.51 and 0.66/100 PYFU in ART naive, currently off and currently on ART patients, respectively. Higher current CD4 count was associated with reduced risk of both infective and non-infective SNAE in naives and in patients on ART (Table 1). The association was less strong in the group which suspended ART (for non-infective SNAE the p value for interaction between current log-CD4 and ART-status, p=0.004). Conversely, we found no association between baseline CD4 count and risk of non-infective SNAE in people treated with ART (p value for interaction = 0.0001). When CVD were considered separately, there was no association with CD4 count (not shown)., Conclusions: Our findings show that, differently from ART naive, in ART-treated patients, non-infective SNAE are predicted by current but not by baseline CD4, suggesting that immune restoration is crucial to prevent these events.

Background: The aim of the study was to evaluate incidence and determinants of bacterial pneumonia (BP) after starting combination antiretroviral therapy (cART) in the Italian Cohort of Antiretroviral-Naive Patients., Methods: Patients free from BP at cART initiation enrolled between 1996 and 2011 were analyzed. Kaplan-Meier curves were calculated to estimate the time to the first episode of BP; uni- and multivariable Cox proportional hazard models, with time-updated covariates, were applied to identify the risk factors of the first episode of BP., Results: Four thousand nine hundred forty-two patients were followed for a median of 63.7 months (interquartile range: 23.6, 106.7); 73% were men, median age 36 years (interquartile range: 32, 42), 35% hepatitis C virus antibody positive, 28% smokers, 15% with an AIDS diagnosis (not BP) before cART, 46% with nadir CD4⁺ T-cell count ≤200 cells per microliter. During 27,569 person years, 137 patients developed 156 BPs, for a crude incidence of 5.66 [95% confidence interval (CI): 4.81 to 6.62] per 1000 person years. The probabilities of first BP at 3, 5, 10, and 14 years from cART initiation were 2.0% ± 0.22%, 2.9% ± 0.28%, 4.3% ± 0.42%, and 5.7% ± 0.75%, respectively. The occurrence of a first BP was associated with low nadir CD4⁺ [hazard ratios (HR) (per 100 cells/μL higher) = 0.86, 95% CI: 0.79 to 0.94], low current CD4 [HR (per 100 cells/μL higher) = 0.88, 95% CI: 0.84 to 0.92], high CD8⁺ [HR (per 100 cells/μL higher) = 1.02, 95% CI: 1.01 to 1.03], low hemoglobin [HR (per g/dL higher) = 0.74, 95% CI: 0.71 to 0.78], and unfavorable virological outcome [HR (HIV-RNA >50 vs <50 copies/mL) = 1.29, 95% CI: 1.04 to 1.60] in addition to older age, male gender, non-Italian nationality, smoking, and longer time to cART initiation., Conclusions: BP is an infrequent clinical event in the cART era and is associated with traditional risk factors, viroimmunological failure to cART, and low hemoglobin.

(Val)ganciclovir is used to treat cytomegalovirus (CMV) infection following solid organ (SOT) or hematopoietic stem cell (HSCT) transplantation. Treatment failures occur, but the contribution from 39 known ganciclovir-related mutations (GRMs) in the CMV-UL97 gene remains controversial. We propose a categorization of these GRMs potentially useful when interpreting sequence analyses in clinical settings. The UL97 gene was sequenced from first/recurrent CMV infections among consecutive SOT or HSCT recipients during 2004-2009. GRMs were categorized as: Signature GRM (sGRM) if in vitro ganciclovir IC(50) ratio for mutated versus wild-type virus >2 (n = 24); polymorphic GRM (pGRM) if ratio <2 (n = 15). (Val)ganciclovir treatment failure was defined as persistent viremia for 30 days or switch to foscarnet within this period. Of 99 (49 HSCT and 50 SOT) recipients with one CMV infection episode, 15 (13 HSCT and 2 SOT) experienced a total of 19 recurrent infection episodes. The prevalence of sGRM was 0% at start of first episode, whereas at start of recurrent episodes, prevalence was 37%. Only one sGRM was present at a time in individual patients. Patients with CMV containing an sGRM (vs. wild type)-but not with a pGRM-were at excess risk of treatment failure (odds ratio = 70.6 [95% CI:8.2-609.6]; p < 0.001). sGRMs emerged only following longer termed use of antiherpetic drugs and usually in recurrent CMV infection episodes. Risk of ganciclovir treatment failure was raised if an sGRM was detected., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective and Design: The present study aims at evaluating the influence of genetic polymorphisms on antiretroviral therapy (ART)-associated lipodystrophy. We included in the study 255 ICoNA. patients and we assessed the distribution of Fas -670 AG polymorphism, ApoC3 -455 CT and -482 CT polymorphisms, C161T silent substitution in the PPAR gamma gene, the Adrenergic beta3 Receptor (ARbeta3) codon 64 TC variant, and two polymorphisms in the Adrenergic beta2 Receptor (ARbeta2) codon 16 AG and codon 27 CG. Crude rates of lipoatrophy and fat accumulation and adjusted relative rates were calculated using Poisson regression., Results: In a multivariate model after adjusting for gender, HIV exposure, age, current viral load, hepatitis C virus (HCV) serology, nucleoside reverse-transcriptase inhibitor (NRTI) pair/'third drugs' currently used, months of pre-highly active antiretroviral therapy (HAART) exposures to NRTI, the following genotypes resulted protective against lipoatrophy: ApoC3 -455 CC genotype [adjusted relative risks (ARR) 0.2, 95% confidence interval (CI) 0.046-0.91 vs CT/TT, P = 0.037], ARbeta3 codon 64 TT genotype (ARR 0.39, 95% CI 0.14-1.06 vs TC/CC, P = 0.066), and Fas -670 GG genotype (ARR 0.51, 95% CI 0.26-1.01 vs AG/AA, P = 0.053). With regard to fat accumulation, in the multivariate model, the ARbeta2 codon 27 CC genotype resulted protective (ARR 0.21, 95% CI 0.08-0.51 vs CG/GG, P = 0.0006), whereas the ARbeta2 codon 16 AA genotype resulted associated with higher risk (ARR 3.72, 95% CI 1.58-8.76 vs AG/GG, P = 0.0026)., Conclusion: Our study suggests that genetic polymorphisms of genes involved in apoptosis and adipocyte metabolism are significantly related to ART associated lipodystrophy. Particularly, we evidenced a role for ApoC3 -455 in lipoatrophy and for the two variants of ARbeta2 in fat accumulation.

Recently, it was shown that cirrhotic patients without human immunodeficiency virus (HIV) infection had low CD4 cell counts and normal CD4 cell percentages, suggesting that, for HIV-infected persons, the CD4 cell percentage might be a more accurate marker of disease progression than the absolute CD4 cell count. In cirrhotic HIV-infected persons in the Italian Cohort of Antiretroviral-Naive Patients, the absolute CD4 cell count seemed to be better predictor of the risk of developing an acquired immunodeficiency syndrome-defining illness than the CD4 cell percentage.

Objective: To assess the risk of clinical progression (CP) according to the duration of time spent without complete viral load (VL) suppression compared with that associated with periods of stably suppressed viremia in HIV-infected people who started highly active antiretroviral therapy (HAART) when previously naïve to antiretrovirals., Design: A cohort study of patients having started HAART after enrollment in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA) and being followed for at least 6 months., Methods: Person-years spent in different categories according to the VL level and the change in VL from the most recent value before the initiation of HAART were calculated. A multivariable Poisson regression model, including potential confounders, was constructed., Results: A total of 3023 patients were studied. The overall rate of CP was 13.4 per 1000 person-years. Evidence for a higher risk of CP was observed for people with a current VL >10,000 copies/mL. For each year longer spent on HAART with a VL >100,000 copies/mL, a 5-fold increased risk was observed (relative risk [RR] = 5.34, 95% confidence interval [CI]: 2.83 to 1.08; P = 0.0001). An increased risk of CP in patients with current suppression <1.5 log10 copies/mL (RR = 2.34, 95% CI: 1.16 to 4.74; P = 0.02) and in those with no suppression or a VL higher than their set point (RR = 2.39, 95% CI: 1.17 to 4.89; P = 0.02) was observed compared with those with suppression of >3 log10 copies/mL, although it was not significant. Longer duration on HAART with a VL suppressed below set point seemed to confer protection against CP., Conclusions: Virologic failure to antiretroviral drugs is common. The risk of CP may remain low despite a low but detectable level of HIV viremia.

Objectives of the study were to assess the differences between sexes in the likelihood of starting antiretroviral therapy (ART), in rates of sustained discontinuation from highly active antiretroviral therapy (HAART), and in clinical progression. In a multicenter cohort study (I.Co.N.A. Study), 2323 men and 1335 women previously naive to antiretrovirals were enrolled. As of September 2002, 807 women and 1480 men started ART. The median time to starting ART was 28 weeks for women and 17 weeks for men (P = 0.0003 by log-rank test). This difference was no longer significant after adjusting for either HIV RNA (P = 0.21) or CD4 count (P = 0.28) at enrollment. Women tend to start HAART less frequently than mono/dual ART after adjusting for potential confounders (odds ratio = 0.78, 95% confidence interval [CI]: 0.60-1.01; P = 0.06). Women who started HAART were 1.4 times more likely than men (95% CI: 1.00-1.99; P = 0.05) to interrupt at least 1 drug because of toxicity. Twenty-one percent of women and 19% of men interrupted HAART altogether for more than 3 months (P = 0.3). Clinical progression was observed in 53 women (22.6%) and 137 men (23.4%; P = 0.56). Risk of developing a clinical event was found to be no different between women and men (relative hazard = 0.84, 95% CI: 0.56-1.26; P = 0.40).

Definition of the time of loss of virological response is important when designing a viral load endpoint for trials of antiretroviral drugs. We assessed whether, in patients who achieved a viral load below 50 copies/ml, two consecutive values above 50 copies/ml was really indicative of loss of response. It was common for the viral load to return to below 50 copies/ml with no change in regimen, suggesting that a higher threshold for defining the loss of response is required.

Background: Subpopulations of HIV with mutations associated with resistance to antiretroviral drugs often have reduced replicative capacity, so virus with resistance mutations for all existing and new antiretroviral drugs is likely to be appreciably impaired. Issues of toxicity, quality of life and economics mean that the simultaneous use of all these drugs in combination is unrealistic. We aimed to explore the use of sequential monotherapy regimens using a mathematical model of quasi-species dynamics, to see if these could take advantage of the poor replicative capacity of highly resistant virus., Methods: We assume for each of seven drugs that a single mutation is associated with the ability to replicate (effective reproductive ratio, R > 1) in the presence of that drug as monotherapy. Parameters included were drug efficacy, the cost of resistance mutations and the number of new target cells arising daily., Results: The use of seven drugs in a daily/weekly sequential monotherapy cycle led to substantial viral suppression (in the presence of all resistant viral subpopulations) for a wider range of parameter values than a continuous five-drug regimen. Although on any one day/week there is a viral subpopulation with R > 1 (e.g. that with resistance only to the current drug), this subpopulation does not have time to grow sufficiently during the short period when that drug is being taken., Conclusion: These results provide a rationale for trials of sequential regimens, using as wide a number of drugs with different resistance-associated mutations as possible, as a potential 'resistance-proof' strategy for achieving significant viral load suppression.

Background: The effect of chronic coinfection with hepatitis viruses on the response to therapy against human immunodeficiency virus 1 (HIV-1) remains debated., Methods: In a prospective cohort study, the effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) serostatus on the outcome of potent HIV-1 therapy was analyzed in HIV-1-infected patients previously naive to antiretroviral therapy. Changes from baseline CD4+ cell counts and HIV RNA levels over time were analyzed by linear regression models. Time to clinical progression and time to reach virologic and immunologic response were analyzed by multivariate Cox proportional hazards regression models., Results: We studied 1320 patients, among whom 600 were HCV antibody-positive and 90 were HBV surface antigen-positive. During a median follow-up of 37 months (range, 1-48 months), clinical progression was observed in 99 patients (56 new acquired immunodeficiency syndrome-defining events and 43 deaths). In multivariate models, HCV-positive HBV-negative patients showed a shorter time to clinical progression (hazard ratio, 1.55; 95% confidence interval, 1.00-2.41). Patients who were HCV-positive also showed mean CD4+ recoveries over time that were at least 30 cells/ micro L fewer than those of seronegative patients. Hepatitis virus serostatus did not affect the virologic response to HIV-1 therapy., Conclusions: Clinical progression of HIV-1 disease after starting potent antiretroviral therapy is accelerated by concomitant infection with HCV. Compared with patients without coinfection, coinfected patients showed impaired CD4+ cell recovery, despite similar virologic response to HIV-1 therapy. These findings may have important implications for the treatment of HCV and for the timing of initiation of HIV-1 therapy in coinfected individuals.

The aim of this study was to assess the relationships among the detection of p24 antigen, human immunodeficiency virus (HIV) RNA level, CD4 cell count, and disease progression in 111 males with hemophilia who were infected with HIV for < or =20 years. Sixty-four individuals (58%) developed p24 antigenemia a median of 11.6 years after seroconversion. The time to first detection of p24 antigen was shorter among those who were older (P=.04) and those with a high initial HIV RNA level (P=.006). The median HIV RNA level and CD4 cell count at the time of the detection of p24 antigen were 4.95 log(10) copies/mL and 100 cells/mm(3), respectively. In univariate analyses, p24 antigenemia was associated with more-rapid progression to AIDS (relative hazard [RH], 5.50; P=.0001). The effect was reduced (RH, 1.85; P=.06) after adjusting for CD4 cell counts and HIV RNA levels during follow-up, age, and calendar year. A significant relationship between p24 antigenemia and death was nonsignificant after adjusting for CD4 cell count.

Objective: To describe the reasons for, and factors associated with, modification and discontinuation of highly active antiretroviral therapy (HAART) regimens at a single clinic., Subjects: A total of 556 patients who started HAART at the Royal Free Hospital were included in analyses. Modification was defined as stopping or switching any antiretrovirals in the regimen, whereas discontinuation was defined as the simultaneous stopping of all antiretrovirals included in the initial regimen. Reasons were classified as immunological/virological failure (IVF) and toxicities and patient choice/poor compliance (TPC)., Results: The median CD4 count at starting HAART was 171 x 10(6) cells/l and viral load 5.07 log copies/ml. During a median follow-up of 14.2 months, 247 patients (44.4%) modified their HAART regimen, 72 due to IVF (29.1%) and 159 due to TPC (64.4%) and a total of 148 patients (26.6%) discontinued HAART. Older patients were less likely to modify HAART [relative hazard (RH), 0.73 per 10 years; P = 0.0008], as were previously treatment-naive patients (RH, 0.65; P = 0.0050), those in a clinical trial (RH, 0.64; P = 0.027) and those who started nelfinavir (RH, 0.57; P = 0.035). Patients who started with four or more drugs (RH, 2.21, P < 0.0001), who included ritonavir in the initial regimen (RH, 1.41; P = 0.035) or who had higher viral loads during follow-up (RH per log increase, 1.51; P < 0.0001) were more likely to modify HAART., Conclusions: There was a high rate of modification and discontinuation of HAART regimens in the first 12 months, particularly due to toxicities, patient choice or poor compliance.

Objectives: To describe the viral response to HAART by weeks 4 and 8 in previously antiretroviral-naive patients. To assess whether the weeks 4 or 8 viral loads are useful predictors of viral suppression by week 24., Design: A large clinical database including 453 antiretroviral-naive patients whose plasma viral load was monitored every 4 weeks., Methods: Observed probabilities of achieving a viral load < or = 500 copies/ml by week 24 (days 84-168) from starting highly active antiretroviral therapy (HAART) were calculated according to viral loads at weeks 4 and 8., Results: A total of 42.4% of patients (153/361) reached < or = 500 copies/ml viral load by week 4 and 70.4% (245/348) by week 8. Viral suppression below 500 copies/ml by 4-8 weeks was similar irrespective of the pre-HAART viral load. In patients with viral loads above 10000 copies/ml at week 4, 60.6% (20/33) achieved < or = 500 copies/ml by week 24. In patients with viral loads still above 10000 copies/ml at week 8, only 42.3% (11/26) achieved < or = 500 copies/ml by week 24, and only 33.3% (3/9) maintained viral suppression below 500 copies/ml to week 48., Conclusion: Viral loads at weeks 4 and 8 should be monitored to detect early signs of low subsequent viral suppression. For previously antiretroviral-naive patients whose viral loads after 8 weeks of HAART are still above 10000, there is an urgent need to assess adherence to therapy, drug levels and resistance, so management can be modified accordingly to reduce the rate of week 24 virological failure.

Human immunodeficiency virus-1 (HIV-1) infection has been shown to result in up-regulation of the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes in vitro and in vivo. The objective of this study was to investigate whether this up-regulation is paralleled by higher serum levels of soluble uPAR (suPAR) in patients with advanced HIV-1 disease and whether the serum level of suPAR is predictive of clinical outcome. Using an enzyme-linked immunosorbent assay, the level of suPAR was measured retrospectively in serum samples from 314 patients with HIV-1 infection. By Kaplan-Meier and Cox regression analyses, the serum suPAR levels were correlated to survival with AIDS-related death as the end point. High levels of serum suPAR (greater than median) were associated with poor overall survival, and Kaplan-Meier analysis on patients stratified by suPAR level demonstrated a continuous increase in mortality rates with higher suPAR levels. After adjustment for accepted prognostic markers-including Centers for Disease Control and Prevention-defined clinical stages, CD4 counts, viral load, beta2-microglobulin, and age-the prognostic strength of suPAR remained highly significant, indicating that the serum suPAR level is a novel, strong, and independent predictor of survival in HIV-1 infection. This report is the first to demonstrate an important association between the plasminogen activator system and disease progression in HIV-1 infection.

It is recommended that randomized controlled trials be analyzed on an intention-to-treat (ITT) basis whereby patients are analyzed in the group to which they were originally assigned, irrespective of the treatment actually received. However, in trials of antiretroviral therapy, it is quite common for patients to withdraw from the trial, and information on virological or immunological endpoints may not be available. The way in which this missing information is dealt with in the analysis can have a large effect on the results of a trial and, therefore, the principle of ITT may be adhered to more closely in some studies than in others. This article describes some simple approaches commonly taken to impute missing data values and discusses the possible effects of these approaches on the results of a trial.

Context: According to recent studies, women have lower plasma HIV RNA concentrations than men. However, these studies did not take into account the duration of HIV infection., Objectives: To analyze the relationship between viral load and gender among individuals with known date of seroconversion., Setting: Sixty infectious disease clinics in Italy., Design: Cross-sectional analysis of data collected at enrollment in a cohort study., Participants: Injecting drug users and heterosexual contacts naive to antiretroviral therapy at enrollment (245 men; 170 women)., Main Outcome Measures: Plasma HIV RNA concentrations, measured using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) or signal amplification b-DNA assays before antiretroviral therapy., Results: Plasma HIV RNA concentrations were similar by age and exposure category (p =.80 and p =.39, respectively). Median viral load among women was roughly half that of men (p =.002). The association between viral load and gender remained significant after fitting a two-way analysis of variance (p =.03) and after adjusting for CD4 count, modality of HIV transmission, and age at enrollment in a regression model. Viral load was 0.27 log10 copies/ml (95% confidence interval, 0.05-0.40; p =.01) lower in women (i.e., 50% lower in the raw scale)., Conclusions: Plasma HIV RNA concentrations were found to be lower among women, even when considering the duration of HIV infection. Compared with men, it is possible women should be given highly aggressive antiretroviral therapy at lower HIV-RNA concentrations.

Objective: To evaluate the frequency of discontinuation of the first highly active antiretroviral regimen (HAART) and the factors predictive of discontinuing for toxicity and failure in a population-based cohort of HIV-positive individuals in Italy, naïve from antiretrovirals at enrolment., Methods: The study population consisted of individuals who initiated HAART and had at least one follow-up visit. The primary end-points were discontinuation of any component of HAART for drug toxicity and discontinuation for failure. Survival analyses were performed to identify predictive factors for reaching the two end-points., Results: Eight hundred and sixty-two individuals initiated HAART; in 727 of them (84.3%) this consisted of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI). Over a median follow-up of 45 weeks, 312 patients (36.2%) discontinued therapy: 182 (21.1%) discontinued due to toxicity, 44 (5.1%) due to failure. The probability of discontinuing HAART at 1 year was 25.5% [95% confidence interval (CI), 21.9-28.9] due to toxicity and 7.6% (95% CI, 4.9-1 0.3) due to failure. Independent factors associated with discontinuation for toxicity were: gender [relative hazard (RH) = 0.51; 95% CI, 0.32-0.80 for men versus women], type of treatment (indinavir-containing regimens, RH = 1.94; 95% CI, 1.10-3.41 and ritonavir-containing regimens, RH = 3.83; 95% CI, 2.09-7.03 versus hard-gell saquinavir) and time spent on treatment (RH = 0.89; 95% CI, 0.80-0.98 for each additional month). Discontinuation due to failure was independently associated with the most recent HIV-RNA (RH = 3.20; 95% CI, 1.74-5.88 for log10 copies/ml higher), and with type of treatment (indinavir-containing regimens, RH = 0.21; 95% CI, 0.06-0.78 and ritonavir-containing regimens, RH = 0.23; 95% CI, 0.04-1.26 versus hard-gell saquinavir)., Conclusions: If the current HAART regimen caused no toxicity, less than 10% of naïve patients discontinue their first HAART regimen because of failure after 1 year from starting therapy.

The interrelationships between the CD4 lymphocyte count, plasma viral load [human immunodeficiency virus (HIV) RNA], beta-2-microglobulin (beta2-M) and immunoglobulin A (IgA) and the mortality risk was explored in 234 HIV-infected individuals (median CD4 count 230 cells/mm3, range 1-1,247). Product-moment correlation analysis was used to study the association between beta2-M, IgA and HIV RNA. A proportional hazards Cox model was used to estimate the relative hazard (RH) of death. Both beta2-M (r = 0.49, p < 0.0001) and IgA (r = 0.42, p < 0.0001) were positively correlated with HIV RNA. High beta2-M levels were associated with an increased risk of death in both univariate Cox analysis and after adjustment for HIV RNA, CD4 lymphocyte count and age [RH = 1.16 per 100 nmol/l higher beta2-M, 95% confidence interval (CI) 1.05-1.27]. Raised IgA levels were associated with shorter survival in individuals with a CD4 count above 50 cells/mm3 in univariate analysis as well as after adjusting for age and CD4 lymphocyte count (RH = 1.19 per 10 micromol/l higher IgA, 95% CI 1.01-1.39). However, this association was no longer significant after further adjusting for HIV RNA. In conclusion, beta2-M levels provided additional prognostic information for survival to the information obtained by CD4 count and HIV RNA levels, whereas serum IgA only was a weak prognostic marker in this fairly progressed cohort.

Objective: To evaluate time trends of the spectrum of AIDS-defining diseases in Italy, 1982-1996., Methods: Surveillance data from the Italian National AIDS Registry were used to assess temporal patterns of all AIDS-defining diseases diagnosed among adults as of December 1996. Twenty-six initial clinical manifestations of AIDS were grouped into 12 categories. Relative frequencies were calculated by year of diagnosis and stratified by age, gender, HIV-exposure category, and CD4+ cell count. A multivariate polychotomous logistic model was used to estimate the proportions of each diagnostic category over time, adjusting simultaneously for the remaining diagnostic categories and for variables of interest., Results: This analysis was based on 41772 diagnoses of AIDS-defining diseases among 36 638 reported cases. Mycoses represented the most frequent condition (27.3%), followed by Pneumocystis carinii pneumonia (PCP) (21.4%) and viral infections (8.9%). Cancers accounted for less than 10% of diseases. Downward trends were observed for mycoses, PCP (in the last part of the study period), Kaposi's sarcoma (KS), and non-Hodgkin's lymphomas (NHL). Upward trends were observed for mycobacterioses, and bacterial and protozoal infections. Brain toxoplasmosis increased up to 1994, and, thereafter, it appeared to decrease. These trends were less marked when the analysis was restricted to the diseases included in the pre- 1987 AIDS definition. Trends stratified by CD4+ cell count for the period 1990-1996 were substantially consistent with the above-reported results., Conclusions: The downward temporal trends in the most recent years of the study period for PCP and for brain toxoplasmosis are likely to be related to the use of prophylactic treatment. This analysis confirms a decline in KS but suggests that this was largely over by 1990.

The ability of cytotoxic T lymphocytes (CTL) to control and influence the outcome of human immunodeficiency virus (HIV) infection is not fully understood. The association between HIV-CTL activity and disease progression was evaluated prospectively in 36 HIV-1-infected individuals with a median follow-up of 3.0 years. HIV-CTL activity was measured in a 4 h Cr* release assay using autologous target cells expressing HIV-1 BRU isolate gene products (gp-120, gag, pol, nef) and a bulk culture of autologous effector cells. The CD4 count was measured at enrolment and plasma HIV RNA was measured retrospectively. The present study failed to support the hypothesis that HIV-CTL activity, as measured using the present method, is important in reducing the risk of death in HIV-infected individuals. However, using other approaches and methods could possibly yield other conclusions, and further prospective studies are needed to examine the relationship between CTL and disease progression.

The association between CD4 cell count and duration of virus load suppression was investigated in 558 patients in the Frankfurt HIV Clinic Cohort who had begun highly active antiretroviral therapy and who had virus load declines to 500 copies/mL; P=.0001). Baseline virus load was not associated with virus load rebound. Lower baseline CD4 cell counts were associated with increased risk of viral rebound; however, this risk was significantly reduced in persons with low baseline CD4 cell counts who experienced substantial increases in CD4 cell counts during follow-up.