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Nationally up to 60 % of persons living with HIV are neither taking antiretroviral therapy (ART) nor well engaged in HIV care, mainly racial/ethnic minorities. This study examined a new culturally targeted multi-component intervention to address emotional, attitudinal, and social/structural barriers to ART initiation and HIV care. Participants (N = 95) were African American/Black and Latino adults with CD4 < 500 cells/mm(3) not taking ART, randomized 1:1 to intervention or control arms, the latter receiving treatment as usual. Primary endpoints were adherence, evaluated via ART concentrations in hair samples, and HIV viral load suppression. The intervention was feasible and acceptable. Eight months post-baseline, intervention participants tended to be more likely to evidence "good" (that is, 7 days/week) adherence (60 vs. 26.7 %; p = 0.087; OR = 3.95), and had lower viral load levels than controls (t(22) = 2.29, p = 0.032; OR = 5.20), both large effect sizes. This highly promising intervention merits further study.

African American/Black and Hispanic persons living with HIV/AIDS ("AABH-PLHA") are under-represented in HIV/AIDS medical studies (HAMS). This paper evaluates the efficacy of a social/behavioral intervention to increase rates of screening for and enrollment into HAMS in these populations. Participants (N = 540) were enrolled into a cluster randomized controlled trial of an intervention designed to overcome multi-level barriers to HAMS. Primary endpoints were rates of screening for and enrollment into therapeutic/treatment-oriented and observational studies. Intervention arm participants were 30 times more likely to be screened than controls (49.3 % vs. 3.7 %; p < .001). Half (55.5 %) of those screened were eligible for HAMS, primarily observational studies. Nine out of ten found eligible enrolled (91.7 %), almost all into observational studies (95.2 %), compared to no enrollments among controls. Achieving appropriate representation of AABH-PLHA in HAMS necessitates modification of study inclusion criteria to increase the proportion found eligible for therapeutic HAMS, in addition to social/behavioral interventions.

Background and Objective: The reasons for minority underrepresentation in HIV/AIDS clinical trials remain unclear. We aimed to evaluate the knowledge, experience, and factors that influence minority participation in HIV/AIDS studies in the United States., Methods: An anonymous, bilingual, self-administered survey on study participation was given to HIV-infected adults attending AIDS Clinical Trials Group-affiliated clinics in the United States and Puerto Rico. Chi-square tests were used to evaluate differences by race, first language, and level of education. Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for factors associated with being talked to about participation in a study., Results: We analyzed 2,175 complete surveys (221 in Spanish). Among respondents, 31% were White, 40% were Black/African American (AA), and 21% were Hispanic. The overall rate of previous participation in any HIV/AIDS study was 48%. Hispanics were less likely to know about studies compared to Whites and AAs (67% vs 74% and 76%, respectively; P < .001). Compared to Whites, AAs and Hispanics were less likely to have been talked to about participating in a study (76% vs 67% and 67%, respectively; P < .001). The OR for being talked to about participating in a study was 0.65 (95% CI, 0.52-0.81) for AAs and 0.65 (95% CI, 0.49-0.85) for Hispanics, compared to Whites. AAs and Hispanics were more likely to state that studies were not friendly to their race (17% and 10% vs 4%; P < .001)., Conclusions: Minorities continue to face barriers for HIV/AIDS trial participation, even when clinical research is available. Enrollment strategies should better target minorities to improve recruitment in HIV/AIDS research.

Background: Pegylated interferon (PEG-IFN)/ribavirin (RBV)-related cytopenias have been associated with improved virological outcomes among hepatitis C virus (HCV)-monoinfected patients. This analysis evaluated PEG-IFN/RBV-related cytopenias with virological responses among HIV/HCV-coinfected patients., Methods: Pooled data from PARADIGM and AIDS Pegasys Ribavirin International CO-infection Trial (APRICOT) trials of HIV/HCV-infected patients treated with PEG-IFN/RBV. Virologic response was categorized as HCV RNA detectable (end of treatment nonresponders [ET-NR]) or nondetectable (end of treatment responders [ETR]). Declines in hemoglobin (Hgb), platelets, neutrophils, lymphocytes, and weight between the groups were compared via analysis of covariance and Cochran-Mantel-Haenszel test., Results: A total of 474 patients, 291 ET-NR and 183 ETR (67 relapsers, 116 with sustained virologic response), 81% male, 52% Caucasian, 88% noncirrhotic, and 67% nondetectable HIV. The ETR experienced greater Hgb declines (≥3.0 g/dL) from baseline (73.8% versus 55.0%; P < .0001), neutrophils ≤1 and ≤ 0.5 × 10(9)/L (66.1% versus 56.4%; P = .0334 and 42.6% versus 33.3%; P = .0312, respectively), and lymphocytes ≤1.5 and ≤0.5 × 10(9)/L (99.5% versus 87.6%; P < .0001 and 24.6% versus 14.9%; P =.0079, respectively)., Conclusions: The HIV/HCV-coinfected patients with ETR experienced greater declines in Hgb, neutrophils, and lymphocytes than the ET-NR patients.

Objective: This study was performed to evaluate a once-daily dual-therapy regimen, maraviroc (MVC) + atazanavir/ritonavir (ATV/r), in treatment-naive patients., Design: A phase 2b, randomized, open-label pilot study., Methods: In Study A4001078 (NCT00827112), treatment-naive patients with CCR5-tropic HIV-1 (HIV-1 RNA ≥1000 copies/mL; CD4 cell count ≥100 cells/mm) were randomized to receive either MVC 150 mg once daily (n = 60) or tenofovir/emtricitabine (TDF/FTC) 300/200 mg once daily (n = 61) + ATV/r 300/100 mg once daily. Primary endpoint was proportion of patients with HIV-1 RNA <50 copies per milliliter at week 48., Results: At week 48, 44 (74.6%) and 51 (83.6%) patients in the MVC and TDF/FTC treatment groups, respectively, had plasma HIV-1 RNA <50 copies per milliliter. Median change from baseline in CD4 cell count at week 48 was +173 and +187 cells per cubic millimeter with MVC and TDF/FTC, respectively. Seven patients discontinued from each arm; there were no deaths. The incidence of serious adverse events (AEs) was similar in each group; however, there were more grade 3/4 AEs in the MVC group (18 vs 11), mostly due to hyperbilirubinemia. Three patients in each arm were evaluable for virological analysis at discontinuation or failure (HIV-1 RNA >500 copies/mL); no genotypic resistance, change in tropism, or loss of susceptibility relevant to treatment was observed., Conclusions: The virological activity and immunological benefit of once-daily MVC + ATV/r were confirmed. Indirect hyperbilirubinemia and associated signs were the most commonly reported AEs in both study treatment groups and were not associated with significant transaminase increases. No drug resistance occurred.

Objectives: We examined the efficacy of a peer-driven intervention to increase rates of screening for AIDS clinical trials among African Americans and Hispanics living with HIV/AIDS., Methods: We used a randomized controlled trial design to examine the efficacy of peer-driven intervention (6 hours of structured sessions and the opportunity to educate 3 peers) compared with a time-matched control intervention. Participants were recruited using respondent-driven sampling (n = 342; 43.9% female; 64.9% African American, 26.6% Hispanic). Most participants (93.3%) completed intervention sessions and 64.9% recruited or educated peers. Baseline and post-baseline interviews (94.4% completed) were computer-assisted. A mixed model was used to examine intervention effects on screening., Results: Screening was much more likely in the peer-driven intervention than in the control arm (adjusted odds ratio [AOR] = 55.0; z = 5.49, P < .001); about half of the participants in the intervention arm (46.0%) were screened compared with 1.6% of controls. The experience of recruiting and educating each peer also increased screening odds among those who were themselves recruited and educated by peers (AOR = 1.4; z = 2.06, P < .05)., Conclusions: Peer-driven intervention was highly efficacious in increasing AIDS clinical trial screening rates among African Americans and Hispanics living with HIV/AIDS.

Persons living with HIV/AIDS (PLHA) of color are under-represented in AIDS clinical trials (ACTs), which may limit the generalizability of research findings and denies many individuals access to high levels of care and new treatments available through ACTs. Disproportionately low rates of recruitment in health care settings and by providers are a major barrier to ACTs for this group. Moreover, PLHA of color are more likely than their white peers to decline to participate, mainly due to fear and mistrust (although willingness is also high), negative social norms about ACTs, and difficulty navigating the unfamiliar ACT system. We describe a small number of successful behavioral and structural interventions to increase the participation of PLHA of color in screening for and enrollment into ACTs. HIV care settings, clinical trials sites, and trial sponsors are uniquely positioned to develop procedures, supports, and trials to increase the proportion of PLHA of color in ACTs.

Background: Pathogenesis studies show that naive CD4 cells are preferentially depleted in lymphoid tissues during HIV infection, and studies of advanced patients suggest levels of naive CD4 cells in blood correlate to total CD4 cells after starting antiretroviral therapy (ARV). We hypothesized that measuring naive CD4 cells in blood in people at earlier stages of disease would identify those at highest risk for poor CD4 reconstitution who may benefit from earlier initiation of ARV., Methods and Findings: We identified 348 patients from multiple AIDS Clinical Trials Group studies who were ARV naive, had a CD4 count between 200 and 500 cells per microliter, a measure of pretreatment-naive CD4 percent, and serial follow-up measures of CD4 count and plasma HIV RNA after starting ARV. We used logistic regression to model the ability of naive CD4 percent to predict 100 and 200 CD4 cell increases after 24 months of therapy. After controlling for baseline viral load and demographic variables, baseline naive but not total CD4 cell count strongly predicted CD4 cell increases. Lower baseline naive CD4 percent was associated with greater time spent at lower CD4 T-cell counts after initiating ARV., Conclusions: Measurement of naive CD4 percent in patients can identify those least likely to reconstitute immunity, who may benefit from earlier ARV treatment.

Acute human immunodeficiency virus type 1 (HIV-1) infection is characterized by high levels of immune activation. Immunomodulation with cyclosporine combined with antiretroviral therapy (ART) in the setting of acute and early HIV-1 infection has been reported to result in enhanced immune reconstitution. Fifty-four individuals with acute and early infection were randomized to receive ART with 4 weeks of cyclosporine versus ART alone. In 48 subjects who completed the study, there were no significant differences between treatment arms in levels of proviral DNA or CD4(+) T cell counts. Adjunctive therapy with cyclosporine in this setting does not provide apparent virologic or immunologic benefit.

Background: Dosing frequency is an important determinant of regimen effectiveness. Methods. To compare efficacy of once-daily (QD) versus twice-daily (BID) antiretroviral therapy, we randomized human immunodeficiency virus (HIV)-positive, treatment-naive patients to lopinavir-ritonavir (LPV/r) administered at a dosage of 400 mg of lopinavir and 100 mg of ritonavir BID (n = 160) or 800 mg of lopinavir and 200 mg of ritonavir QD (n = 161), plus either emtricitabine 200 mg QD and extended-release stavudine at a dosage of 100 mg QD or tenofovir at a dosage of 300 mg QD. Randomization was stratified by screening HIV RNA level <100,000 copies/mL versus > or = 100,000 copies/mL. The primary efficacy end point was sustained virologic response (SVR; defined as reaching and maintaining an HIV RNA level <200 copies/mL) through week 48., Results: Subjects were 78% male, 33% Hispanic, and 34% black. A total of 82% of subjects completed the study, and 71% continued to receive the initially assigned dosage schedule. The probability of SVR did not differ significantly for the BID versus QD comparison, with an absolute proportional difference of 0.03 (95% confidence interval [CI], -0.07 to 0.12). The comparison depended on the screening RNA stratum (P=.038); in the higher RNA stratum, the probability of SVR was significantly better in the BID arm than in the QD arm: 0.89 (95% CI, 0.79-0.94) versus 0.76 (95% CI, 0.64-0.84), a difference of 0.13 (95% CI, 0.01-0.25). Lopinavir trough plasma concentrations were higher with BID dosing. Adherence to prescribed doses of LPV/r was 90.6% in the QD arm versus 79.9% in the BID arm (P<.001). Conclusions. Although subjects assigned to QD regimens had better adherence, overall treatment outcomes were similar in the QD and BID arms. Subjects with HIV RNA levels > or =100,000 copies/mL had better SVR with BID regimens at 48 weeks, which suggests a possible advantage in this setting for more frequent dosing. Clinical trial registration. ClinicalTrials.gov registration number: NCT00036452.

Targeting canarypox (CP)-HIV vaccine to dendritic cells (DCs) elicits anti-HIV-1 immune responses in vitro. We conducted a phase I/II clinical trial to evaluate whether adding DC to a CP-HIV vaccine improved virologic control during analytic treatment interruption (ATI) in HIV-1-infected subjects. Twenty-nine subjects on suppressive antiretroviral therapy were randomized to vaccination with autologous DCs infected with CP-HIV+keyhole limpet hemocyanin (KLH) (arm A, n=14) or CP-HIV+KLH alone (arm B, n=15). The mean viral load (VL) setpoint during ATI did not differ between subjects in arms A and B. A higher percentage of subjects in the DC group had a VL setpoint < 5,000 c/mL during ATI (4/13 or 31% in arm A compared with 0/13 in arm B, p=0.096), but virologic control was transient. Subjects in arm A had a greater increase in KLH lymphoproliferative response than subjects in arm B; however, summed ELISPOT responses to HIV-1 antigens did not differ by treatment arm. We conclude that a DC-CP-HIV vaccine is well-tolerated in HIV-1-infected patients, but does not lower VL setpoint during ATI compared with CP-HIV alone. New methods to enhance the immunogenicity and antiviral efficacy of DC-based vaccines for HIV-1 infection are needed.

Manifestations of viral infections can differ between women and men, and marked sex differences have been described in the course of HIV-1 disease. HIV-1-infected women tend to have lower viral loads early in HIV-1 infection but progress faster to AIDS for a given viral load than men. Here we show substantial sex differences in the response of plasmacytoid dendritic cells (pDCs) to HIV-1. pDCs derived from women produce markedly more interferon-alpha (IFN-alpha) in response to HIV-1-encoded Toll-like receptor 7 (TLR7) ligands than pDCs derived from men, resulting in stronger secondary activation of CD8(+) T cells. In line with these in vitro studies, treatment-naive women chronically infected with HIV-1 had considerably higher levels of CD8(+) T cell activation than men after adjusting for viral load. These data show that sex differences in TLR-mediated activation of pDCs may account for higher immune activation in women compared to men at a given HIV-1 viral load and provide a mechanism by which the same level of viral replication might result in faster HIV-1 disease progression in women compared to men. Modulation of the TLR7 pathway in pDCs may therefore represent a new approach to reduce HIV-1-associated pathology.

Background: Success of antiretroviral therapy depends on high rates of adherence, but few interventions are effective. Our objective was to determine if modified directly observed therapy (mDOT) improves initial antiretroviral success., Methods: In an open-label, randomized trial comparing mDOT (Monday-Friday for 24 weeks) and self-administered therapy with lopinavir/ritonavir soft gel capsules (800 mg/200 mg), emtricitabine (200 mg), and either extended-release stavudine (100 mg) or tenofovir (300 mg), all taken once daily, 82 participants received mDOT and 161, self-administered therapy. Participant eligibility included a plasma human immunodeficiency virus RNA level higher than 2000 copies/mL and being naïve to antiretroviral therapy. A total of 243 participants were predominantly male (79%) (median age, 38 years), with 84 Latinos (35%), 74 non-Latino blacks (30%), and 79 non-Latino whites (33%). The study was conducted at 23 AIDS Clinical Trials Group (ACTG) sites in the United States and 1 site in South Africa between October 2002 and January 2006. The primary outcome was virologic success at week 24 and secondary outcomes were virologic success, clinical progression, and adherence at week 48., Results: Over 24 weeks, mDOT had greater virologic success (0.91; 95% confidence interval [CI], 0.81 to 0.95) than self-administered therapy (0.84; 95% CI, 0.77 to 0.89), but the difference (0.07; lower bound 95% CI, -0.01) did not reach the prespecified threshold of 0.075. Over 48 weeks, virologic success was not significantly different between mDOT (0.72; 95% CI, 0.61 to 0.81) and self-administered therapy (0.78; 95% CI, 0.70 to 0.84) (difference, -0.06; 95% CI, -0.18 to 0.07 [P = .19])., Conclusions: The potential benefit of mDOT was marginal and not sustained after discontinuation. Modified DOT should not be incorporated routinely for care of treatment-naïve human immunodeficiency virus type 1-infected patients.

HIV-seropositive blacks, Hispanics, women of all ethnicities, and injection drug users (IDUs) have low rates of clinical trial participation. The opinions of research nurses and study coordinators as potential facilitators and barriers to access to clinical trials may contribute to this disparity. Study coordinators and research nurses from the adult AIDS Clinical Trials Group (ACTG) clinical trials units responded to an anonymous computer-based survey comprising multiple choice questions and clinical scenarios. Descriptive statistics were used to determine frequencies of responses. Recruitment rates of blacks, Hispanics, women and IDUs were mostly rated appropriate compared with the geographic region demographics. Most sites ranked white men as being the most interested in clinical trials. Sites rated their most effective interactions were with white men. Respondents felt they were less likely to enroll individuals who had missed previous clinical appointments or did not speak English. Perceptions that IDUs, Hispanics, blacks, and, to a lesser extent, women had less interest in clinical trials participation than white males may affect recruitment of the targeted populations. Interventions to improve interactions with targeted populations and to remove logistical and language barriers may improve the diversity of clinical trial participants.

Objective: To describe anemia prevalence and correlates with biomarkers and antiretroviral therapy (ART) in HIV/AIDS., Methods: Multicenter, cross-sectional study; clinical laboratory data collected at single visits, including hemoglobin (Hb), CD4+ count, HIV-1 RNA. Patients receiving care at US physician offices during the year 2000. Main outcome measure was anemia (Hb < 14 g/dL [men]; < 12 g/dL [women]) and marked anemia (Hb < 11 g/dL [men]; < 10 g/dL [women]) prevalence. Multivariable models examined association of anemia prevalence with HIV-1 biomarkers and ART., Results: Among 9690 patients, prevalence of anemia and marked anemia was 36% and 5%, respectively. Among 1721 patients receiving no ART, 39.7% were anemic; among 7252 receiving highly active antiretroviral therapy (HAART), 35.5% were anemic (p = 0.001). Anemia was most prevalent among men (37.3 vs. 32.3%; p = 0.0008), blacks (49 vs. 26% [whites]; p < 0.0001), patients with CD4+ < 200 cells/mm(3) (57 vs. 23% [> or = 500 CD4+]; p < 0.00001), and HIV-1 RNA > 30 000 copies/ml (53 vs. 30% [< 500 copies/ml]; p < 0.00001). Marked anemia was more common in women (6.8 vs. 4.3%; p < 0.0001). Among treated patients, logistic regression analysis controlling for CD4+, HIV-1 RNA, sex, and ethnicity, zidovudine (ZDV)-containing regimens (except combination with saquinavir/ZDV/lamivudine) were associated with increased overall anemia risk (odds ratio, 1.39 : 1.74). No regimen was associated with increased risk for marked anemia. Multivariable logistic regression showed CD4+, sex, and ethnicity more strongly associated with anemia than any ART regimen., Conclusion: This large, single-visit, cross-sectional, US-based study shows that anemia remains highly prevalent in HIV-infected patients. Data from this analysis suggest low CD4+ count, black ethnicity, and male sex are consistently strongest correlates of overall anemia; women are significantly more likely to have marked anemia.

Strategies to limit life-long dependence on antiretroviral therapy (ART) are needed. We randomized 81 human immunodeficiency virus (HIV)-infected subjects to 4 interventional arms involving continued ART plus ALVAC vCP1452 (or placebo) with or without interleukin (IL)-2 infusions. Viral load rebound 12 weeks after ART interruption was then analyzed to assess immune control. Fifty-two subjects reached the study end point. ALVAC recipients had 0.5 log(10) lower virologic rebounds (P=.033). IL-2 plus vaccine boosted CD4(+) T cell counts (P<.001) but did not diminish viral rebound. Significant changes were not detected for HIV-specific lymphoproliferative responses in any arm. This exploratory protocol provides useful clinical data for future therapeutic immunization trial design.

Racial/ethnic minorities and women are under-represented in AIDS clinical trials (ACTs). We examined gender differences in willingness to participate in ACTs among urban HIV-infected individuals (N = 286). Sixty percent of participants were male, and most were from racial/ethnic minority backgrounds (55% African-American, 34% Latino/Hispanic, 11% White/other). Knowledge of ACTs was poor. Males and females did not differ substantially in their distrust of AIDS scientists, or in barriers to ACTs. Almost all (87%) were somewhat or very willing to join ACTs. Females were less willing than males to join, including trials testing new medications or new medication combinations. Males and females differed in correlates of willingness to participate in ACTs. Despite long-standing barriers to medical research among minorities and women, willingness to participate was substantial, particularly for men, although the factors that might motivate them to join differed by gender. Women appeared more averse to trials involving new anti-retroviral regimens than men. Gender-specific outreach, behavioural intervention, and social marketing efforts are needed.

Objective: To assess trends in HIV, hepatitis C virus (HCV) and HIV/HCV infection among injecting drug users (IDU) from 1990 to 2001 in New York City. The 1990-2001 time period included a very large expansion of syringe exchange in New York City, from 250,000 to 3,000,000 syringes exchanged annually., Methods: Cross-sectional seroprevalence surveys of IDU entering drug abuse treatment in New York City, with sample sizes for HCV of 72 in 1990-1991 and 412 in 2000-2001. A structured risk behavior questionnaire was administered, and HIV and HCV testing were conducted. HCV testing was performed on de-linked stored serum samples., Results: Over the 1990-2001 period, HIV prevalence declined from 54 to 13%. HCV prevalence declined from 80 to 59% among HIV-seronegative individuals, and from 90 to 63% overall. The estimated HCV incidence in 2000-2001 among new injectors was 18 per 100 person-years at risk., Conclusions: The large-scale expansion of syringe exchange was temporally associated with large reductions in both HIV and HCV prevalence. The prevalence and incidence of HCV, however, still remain at high levels among IDU in New York City.

Objectives: We sought to estimate HIV incidence among injection drug users (IDUs) in New York City from 1990 to 2002 to assess the impact of an expansion of syringe exchange services. Syringe exchange increased greatly during this period, from 250,000 to 3,000,000 syringes exchanged annually., Methods: Serum samples were obtained from serial cross-sectional surveys of 3,651 IDUs. HIV-positive samples were tested with the Serologic Test Algorithm for Recent HIV Seroconversion (STARHS) assay to identify recent HIV infections and to estimate HIV incidence. Consistency with other incidence studies was used to assess strengths and limitations of STARHS., Results: HIV incidence declined from 3.55/100 person-years at risk (PYAR) from 1990-1992, to 2.63/100 PYAR from 1993-1995, to 1.05/100 PYAR from 1996-1998, and to 0.77/100 PYAR from 1999-2002 (P<.001). There was a very strong negative linear relationship (r= -.99, P<.005) between the annual numbers of syringes exchanged and estimated HIV incidence. These results were highly consistent with a large number of shorter incidence studies among IDUs conducted during the time period., Conclusions: STARHS testing of samples from large serial cross-sectional surveys can provide important data for the assessment of community-level HIV prevention.

Background: CD4+ T lymphocyte (CD4) counts and plasma human immunodeficiency virus (HIV) type 1 RNA concentrations predict clinical outcome in HIV-1 infection. Our objective was to assess the independent prognostic value for disease progression of soluble markers of immune system activation., Methods: This retrospective marker-validation study utilized previously obtained clinical and laboratory data, including CD4+ cell counts, and made use of stored frozen serum samples to assay for levels of beta2-microglobulin, neopterin, endogenous interferon, triglycerides, interleukin-6, soluble tumor necrosis factor- alpha receptor II, and HIV-1 RNA, and to determine HIV genotypic reverse-transcriptase inhibitor resistance. The 152 patients who participated in this study represented a subsample of participants in AIDS Clinical Trials Group (ACTG) 116B/117, a randomized trial that demonstrated the clinical benefit of didanosine over zidovudine monotherapy in persons with advanced HIV-1 infection. Marker data were analyzed in relation to protocol-defined clinical disease progression, using Cox proportional hazards models., Results: The median duration of follow-up was 344 days. Elevated baseline values for neopterin (P=.0009), endogenous interferon (P=.00039) and interleukin-6 (P=.0007) were each associated with greater subsequent risk of clinical disease progression. In a head-to-head comparison that was adjusted for CD4+ cell count (P=.0165) and HIV-1 RNA level (P=.1220), we found that elevated values for neopterin (P=.0002) and, to a lesser extent, endogenous interferon (P=.0053) were the strongest predictors of increased risk of clinical disease progression 6 months later., Conclusions: Soluble markers of immune activation add prognostic information to CD4 counts and viral load for risk of disease progression in advanced HIV-1 infection. The robust performance of neopterin, an inexpensive and reliably measured serum marker, supports its potential suitability for patient monitoring, particularly in resource-limited settings.

Background: Although initiation of potent antiretroviral therapy (ART) has significantly improved immune perturbations in individuals with AIDS, it is unclear which factors are most important in determining the degree of immune reconstitution., Methods: Whole blood was analyzed at baseline and week 12 in six groups of subjects (n = 81): those with acute or following immune reconstitution after Pneumocystis jirovecii (previously known as Pneumocystis carinii) pneumonia (PcP) (two groups) and cytomegalovirus (CMV) retinitis (two groups), HIV-infection without AIDS (one group), and healthy volunteers (one group). Absolute CD4+ and CD8+ T lymphocytes, naive (CD45RA+) and memory (CD45RO+) CD4+ T lymphocytes and percentages of activated CD8+ T lymphocytes (CD8+/CD38+/HLA-DR), and CD28 expression on CD4+ and CD8+ T lymphocytes were enumerated., Results: The reconstituted CMV group, which had a history of a lower CD4+ T lymphocyte nadir compared to the reconstituted PcP group (15 cells/mm(3) versus 48 cells/mm(3); p = .013), had significantly lower absolute CD4+, CD8+ and naive CD4+ T lymphocytes and a trend toward lower memory CD4+ T lymphocytes compared to the reconstituted PcP group. Moreover, no difference was noted between the reconstituted groups in the proportion of subjects with undetected HIV-1 RNA. The reconstituted subjects had significantly lower absolute CD4+, memory CD4+ and naive CD4+ T lymphocytes than the HIV-positive controls and a significantly higher percentage of activated CD8+ T lymphocytes with a lower percentage of CD8+CD28 expression than the HIV-negative controls., Conclusion: The association of CD4+ T lymphocyte nadir with the extent of immune reconstitution in HIV-infected individuals suggests that HIV-1 may cause irreparable immune system damage despite potent ART.

Background: Few studies have prospectively evaluated the impact of highly active antiretroviral therapy (HAART) on body weight and lean body mass (LBM) or explored the impact of baseline immunologic or virological changes on these parameters., Methods: Adult AIDS Clinical Trials Group (ACTG) protocol 892 was a prospective, 48-week, multisite observational study of body composition conducted during 1997-2000 among 224 antiretroviral-naive and antiretroviral-experienced subjects coenrolled into various adult ACTG antiretroviral studies. Assessments included human immunodeficiency virus type 1 (HIV-1) RNA load (by polymerase chain reaction); T lymphocyte subset analysis; Karnofsky score; height (baseline only); weight, LBM, and fat (by bioelectrical impedance analysis); and functional performance (by questionnaire)., Results: Overall, only modest median increases in body weight (1.9 kg) and LBM (0.6 kg) occurred after 16 weeks of therapy. Significantly greater median increases in body weight (2.1 vs. 0.5 kg; P=.045) occurred in subjects who achieved virological suppression (HIV-1 RNA load, <500 copies/mL) at week 16 than in subjects who did not. Subjects who were antiretroviral naive at baseline gained more weight (median increase in body weight, 2.6 vs. 0.0 kg; P<.001) and LBM (1.0 vs. 0.1 kg; P=.002) after 16 weeks of treatment than did subjects who were antiretroviral experienced. Subjects with lower baseline CD4 cell counts (<200 cells/mm3) and subjects with higher baseline HIV-1 RNA loads (> or =100,000 copies/mL) were more likely to show increases in LBM of >1.5 kg (P=.013 and P=.005, respectively)., Conclusions: HAART had modestly favorable effects on body composition, particularly in patients with greater pretreatment immunocompromise and virological compromise. The difference between antiretroviral-naive and antiretroviral-experienced subjects with regard to the ability to achieve increased body weight and LBM requires more study.

To determine whether markers of T cell activation and maturation are independently predictive of the response to potent antiretroviral therapy, the Immunophenotypic Markers and Antiretroviral Therapy study applied a novel data-sharing strategy across 5 Adult AIDS Clinical Trial Group trials that counted naive and activated CD4(+) and CD8(+) T cells in 324 subjects. Regression models--adjustment for baseline CD4 cell count, human immunodeficiency virus (HIV) RNA, and study--revealed that high pretreatment CD8(+) T cell activation predicted virologic failure (P=.046). Additional models showed the greatest increase in CD4(+) T cell counts in subjects with highest pretreatment naive CD4(+) T cell counts (P<.0001), which was enhanced by high CD4(+) and low CD8(+) T cell activation. Total lymphocyte count also predicted a subsequent CD4(+) T cell change. These results document the utility of T cell markers in predicting treatment outcome and their potential value for the study and management of HIV-1 infection.

Anemia in human immunodeficiency virus (HIV)-infected patients can have serious implications, which vary from functional and quality-of-life decrements to an association with disease progression and decreased survival. In 2002, 16 members of the Anemia in HIV Working Group, an expert panel of physicians involved in the care of HIV-infected patients that met first in 1998, reconvened to assess new data and to translate these data into evidence-based treatment guidelines. The group reached consensus on the prevalence of anemia in the highly active antiretroviral therapy era; the risk factors that are independently associated with the development of anemia; the impact of anemia on quality of life, physical functioning, and survival; the impact of the treatment of hepatitis C virus coinfection on anemia in HIV-infected patients; evidence-based guidelines for treatment of anemia in HIV-infected patients, including the therapeutic role of epoetin alfa; and directions for future research.

Context: Approaches to preserve or enhance immune function in HIV-1 infection are needed., Objectives: To examine the ability of daily low-dose interleukin-2 (IL-2) in combination with antiretroviral therapy to preserve circulating CD4+ T-cell counts, the clinical safety and tolerability of this treatment, and safety with respect to changes in plasma HIV-1 RNA levels., Design: Twenty-four-week, phase 2, multicenter, randomized, open-label trial conducted at 12 AIDS Clinical Trials Units between September 1995 and May 1997., Participants: A total of 115 HIV-infected persons with screening CD4+ T-cell counts between 300 and 700 cells/mm who were on stable single- or dual-nucleoside therapy for at least 2 months, 11% of whom were also on a protease inhibitor at study entry., Interventions: Patients were randomly assigned to receive IL-2 at a dose of 1 million IU subcutaneously once daily plus continued anti-retroviral therapy (ART + IL-2, n = 57) vs. continued ART alone (ART alone, n = 58). IL-2 dose reductions were made for objective or subjective toxicities. All subjects randomly assigned to the IL-2 arm who interrupted ART were also required to discontinue IL-2 for the same period., Main Outcome Measures: The primary endpoint was a decrease in CD4 T-cell count from baseline; the safety analysis was based on change in plasma HIV RNA by bDNA; and clinical safety and tolerability were analyzed by standard clinical criteria., Results: Of the patients with a baseline CD4 T-cell count recorded, 15 (27%) of 55 patients randomly assigned to ART alone had a drop of > or =25% in their CD4 T-cell count and 23 (41%) of 56 patients randomly assigned to ART + IL-2 had a drop of > or =25% in their CD4 T-cell count at some time over the 24 weeks of the study. This difference was not statistically significant. There was a statistically significant greater variance in CD4 T-cell counts in the IL-2-treated group. More patients in the IL-2 group had at least a 25% increase in CD4 T-cell counts over baseline (34 vs. 13%, P = 0.007). A comparison of grade 3 or worse toxicity showed no differences between the arms, but IL-2 was associated with significantly more grade 2 or worse general body symptoms, primarily discomfort and fatigue. There was no significant difference between the groups with regard to changes in plasma HIV RNA, lymphocyte proliferation, natural killer cell activity, skin test responses to recall antigens, or antibody responses to immunization. Plasma markers of immune activation all increased significantly in IL-2 recipients., Conclusions: In patients with baseline CD4 T-cell counts > or =300 cells/mm primarily treated with single- or dual-nucleoside ART, subcutaneously administered IL-2 at a dose of 1 million IU daily for up to 24 weeks had low toxicity but showed no consistent benefit in preventing decline in CD4 T-cell counts and minimal evidence of immunologic improvement vs. continued ART alone.

Objective: To assess recent developments in the HIV epidemic in injecting drug users (IDUs) in New York City. With >50,000 cases of AIDS in IDUs, New York has experienced the largest HIV/AIDS epidemic in IDUs of any city in the world., Methods: Serial cross-sectional surveys conducted continuously from 1990 to 2001 of IDUs entering the Beth Israel Medical Center (BIMC) drug detoxification program in New York City. HIV serostatus, use of prevention services, and risk behaviors were measured. Individuals were permitted to participate multiple times in the surveys but not more than once in any year., Results: Two thousand eight hundred eighty-seven individuals contributed 3100 observations from 1990 to 2001. There was a substantial and consistent decline in the prevalence of HIV infection among IDUs entering the BIMC detoxification program, from 54% (165/304) in 1991 to 13% (39/303) in 2001 (P < 0.0001). The decline was highly linear, with r2 = 0.92 and a slope of -3.7% in seroprevalence per year. The decline occurred for both males and females, both short and long-term IDUs, and the three largest racial/ethnic subgroups (all P < 0.001 by Cochran-Armitage testing). Use of HIV prevention services increased substantially, particularly syringe exchange and voluntary HIV counseling and testing. General reductions in injection risk behaviors occurred, but substantial numbers of IDUs continued to engage in both receptive and distributive syringe sharing. Two conditional types of risk reduction not currently recommended by health authorities were reported: "informed altruism," in which persons who knew that they were HIV seropositive reduced transmission behavior, and "partner restriction," in which persons who shared needles and syringes primarily confined this sharing within small social networks., Conclusions: HIV infection continues to decline in this population of IDUs in New York City, suggesting the possibility of bringing very high prevalence epidemics under control. Risk elimination may not be required; rather, multiple forms of risk reduction may be effective in reducing HIV transmission within a local population of IDUs.

The safety, pharmacokinetics, and antiviral activity of lopinavir, a human immunodeficiency virus (HIV) protease inhibitor, coformulated with ritonavir as a pharmacokinetic enhancer were evaluated in 38 antiretroviral-naive patients randomized 1:1 to receive open-label lopinavir/ritonavir at a dose of 800/200 mg once daily or 400/100 mg twice daily, each in combination with stavudine and lamivudine twice daily, for 48 weeks. Over the course of 48 weeks, median predose concentrations of lopinavir exceeded the protein-binding corrected concentration required to inhibit replication of wild-type HIV by 50% in vitro by 40- and 84-fold in the once- and twice-daily groups, respectively. Predose concentrations of lopinavir were more variable in the once-daily group (mean +/- SD, 3.62+/-3.38 microg/mL for the once-daily group and 7.13+/-2.93 microg/mL for the twice-daily group). At week 48, in an intent-to-treat (missing = failure) analysis, 74% of patients in the once-daily group and 79% of patients in the twice-daily group had HIV RNA levels of <50 copies/mL (P=.70). Study drug-related discontinuations occurred in 1 patient in each treatment group. Genotypic resistance testing of 4 patients with HIV RNA levels >400 copies/mL between weeks 24 and 48 demonstrated no protease inhibitor-resistance mutations.

Objectives: To examine the extent of immune reconstitution in treatment-naive patients with CD4 T-cell counts <500 cells/microL following 48 weeks of highly active antiretroviral therapy (HAART)., Methods: Thirteen antiretroviral naive patients were evaluated longitudinally for 48 weeks on HAART utilizing immune functional and lymphocyte phenotyping assays, including lymphocyte proliferation assay, flow cytometric evaluation of cell surface markers, and delayed type hypersensitivity skin tests. Virologic responses were monitored using commercially available viral load assays and gag/pol mRNA quantification using simultaneous immunophenotyping/UltraSensitive fluorescence in situ hybridization (ViroTect In Cell HIV-1 Detection Kit; Invirion, Frankfort, MI). Thymic function was evaluated for a subset of four patients using real-time polymerase chain reaction (PCR) for T-cell receptor excision circle (TREC) quantification and thymic scans using computerized axial tomography (CT) of the thymus., Results: HAART initiation resulted in a significant decline in plasma viremia and percentage of infected peripheral blood cells, and a rise in CD4 T cells from a baseline median of 207 cells/microL to a week-48 median of 617 cells/microL. The rise was predominately in CD4 memory cells. Naive T cells also increased in number, but at a slower rate. Activated (HLA-DR CD38) CD4 and CD8 T cells were elevated at baseline (24 and 62%, respectively) and declined by week 48 (17 and 36%, respectively) but did not reach normal levels. The number of Fas CD4 T cells increased from a baseline median of 169 to 381 cells/microL at week 48. Both soluble interleukin (IL)-2 and tumour necrosis factor (TNF) II receptors declined by week 48. HIV p24 lymphocyte proliferation assay responses were transiently detected in three patients. TREC values increased from a median 6400 copies/microg at baseline to a week-48 median value of 26 697 copies/microg., Conclusion: Immune functional reconstitution was not achieved in these HAART naive patients.

We compared immune restoration in patients who suppressed human immunodeficiency virus type 1 replication after treatment with a protease inhibitor (PI) plus nevirapine or with 3 nucleoside reverse-transcriptase inhibitors (NRTIs) plus nevirapine. Changes in total and memory CD4 and CD8 cells were similar in the groups, as were decreases in immune activation (e.g., CD38 and HLA-DR) and increases in CD28 expression. Increases in naive CD4 and CD8 cells tended to be greater in the NRTI-treated group, with differences in naive CD4 cells significant at weeks 8 and 12 (P<.05) but not at week 48. Lymphocyte apoptosis decreased in both groups, but the week-1 decrease was greater in the PI-treated group (P<.02). Lymphocyte proliferation and skin-test responses were comparable. We find little evidence for differences in the major direct immunologic effect of PI versus NRTI regimens and propose that effects observed elsewhere were indirect, mediated through antiviral activity or adaptation of the virus to selection pressure.

It is unclear why discordant immunologic and virologic responses occur during therapy for human immunodeficiency virus (HIV) infection. This study examined whether markers of immune activation and naive/memory lymphocyte subsets at study baseline could predict discordance between HIV type 1 (HIV-1) RNA and CD4+ lymphocyte responses at week 24 of antiretroviral therapy. Ten diverse, prospective antiretroviral studies with 1007 evaluable subjects were included. Subsets of subjects at increased risk for discordance were identified by recursive partitioning. The strongest predictor of more-favorable immunologic than virologic responses was a lower baseline CD4+ lymphocyte count. Weaker predictors in small subsets of subjects were fewer activated CD4+ lymphocytes and fewer CD8+ lymphocytes. Conversely, the strongest predictors of more-favorable virologic than immunologic responses were higher baseline CD4+ lymphocyte count and percentage. Additional predictors in some analyses were higher CD8+ lymphocyte count or percentage and lower HIV-1 RNA concentrations. Baseline markers of immune activation and naive/memory lymphocyte subsets had limited ability to predict subsequent discordance.

Anemia is a multifactorial problem in patients with human immunodeficiency virus (HIV) infection, cancer, and hepatitis C virus (HCV) infection. New insights regarding anemia symptoms and quality of life (QOL) have prompted reassessment of traditional triggers for anemia treatment to increase hemoglobin (Hb) and improve QOL. In HIV-positive patients, anemia is independently associated with disease progression and survival. Many HIV-positive patients receiving highly active antiretroviral therapy (HAART) still develop mild to moderate anemia and associated QOL impairment. Epoetin alfa effectively increases Hb and improves QOL in these patients. Many HIV-positive patients are coinfected with HCV. Standard HCV therapy (interferon alfa/ribavirin) can cause anemia that may result in treatment alterations and compromised virologic outcome. Epoetin alfa therapy in anemic HCV patients increases Hb levels and may provide other benefits. Neuroprotective effects of epoetin alfa in preclinical models of central nervous system disorders have recently been demonstrated, implying a new therapeutic role for this cytokine.

The effect of etanercept, a soluble p75 tumor necrosis factor (TNF) receptor:Fc fusion protein (Enbrel; Immunex, Seattle, WA) on plasma cytokines was evaluated in 11 HIV-infected subjects receiving highly active antiretroviral therapy (HAART) for 28 weeks with or without subcutaneous or intravenous recombinant human interleukin 2 (rhIL-2). Plasma IL-6 and C-reactive protein (CRP) levels increased after rhIL-2 treatment. Etanercept pretreatment attenuated these increases. Median plasma IL-6 levels were 20.29 pg/ml 4 days after rhIL-2 and 7.87 pg/ml 4 days after etanercept and rhIL-2 (p = 0.22); median CRP levels were 78.73 and 46.16 microg/ml, respectively (p = 0.03). An effect on TNF bioactivity could not be assessed as all measurements were below limits of detection. No significant changes were seen in temperature or plasma levels of IL-4, IL-10, IL-12, interferon gamma, or HIV-1 RNA levels. All subjects had undetectable or low-level HIV-1 RNA levels before etanercept dosing. One subject died; however, her death was thought to be unrelated to etanercept. Pretreatment with etanercept may blunt activation of IL-6 and CRP expression induced by rhIL-2. The safety and utility of etanercept in HIV-infected persons should be explored further.

Objective: To determine the effects of nevirapine (NVP), a nonnucleoside reverse-transcriptase inhibitor of HIV-1 and P450 inducer, on the pharmacokinetics (PK) of ethinyl estradiol (EE)/norethindrone (NET), a widely used oral contraceptive, and to assess the effects of EE/NET on the steady-state PK of NVP., Methods: Ten HIV-1-infected women underwent intensive PK sampling after single-dose administration of EE/NET (days 0-1). Oral NVP 200 mg once daily (days 2-15), followed by 200 mg twice daily (days 16-29), was added to background potent antiretroviral therapy. On day 30, intensive PK sampling was performed after concurrent administration of NVP 200 mg and a single dose of EE/NET., Results: Concomitant administration of NVP at steady state with EE/NET resulted in a significant (29%) median reduction in the area under the plasma concentration time curve (AUC(infinity)) and a significant reduction in mean residence time (MRT) and half-life (t(1/2)) of EE. There was a significant (18%) median reduction in the AUC(infinity) for NET that was not associated with a detectable change in NET C(max), MRT, or t(1/2)., Conclusion: Oral contraceptives should not be the primary method of birth control in women of child-bearing potential who are treated with NVP.

Objective: Earlier open-label clinical trials have provided conflicting data on the effects of cyclosporin-A (CsA) on the clinical course and immune status of patients with HIV disease. With the prospects for wider use of CsA in the setting of solid organ transplantation in HIV-infected persons, data on the safety and immunologic activity of this agent are needed. We report here the results of a randomized, double-blind, placebo-controlled trial to assess the safety and immunologic activity of CsA administration in early HIV disease., Methods: Twenty-eight patients with confirmed HIV infection, CD4 cell counts greater than 500 x 106/L, and plasma HIV RNA >600 copies/mL were randomized to receive 2 mg/kg of CsA (Neoral) twice daily or identical placebo for 12 weeks. Subjects were stratified for the presence or absence of stable concomitant antiviral therapy. The primary end point was the effect of therapy on immune activation as assessed by the levels of soluble interleukin-2 receptors. Secondary end points included safety and effects of treatment on plasma HIV RNA, CD4 cell count, and other markers of immune activation and function., Results: The low dose of CsA used in this study did not suppress immune activation or increase circulating CD4 cell counts. Delayed-type hypersensitivity responses were not affected; however, lymphocyte proliferative responses tended to decrease. CsA-treated patients experienced a small but significant rise in plasma HIV RNA levels., Conclusions: Low-dose CsA has no benefit in patients with stable early HIV disease, and its administration may be associated with an increase in plasma HIV RNA. The use of CsA in HIV-infected patients undergoing organ transplantation should be undertaken with caution

Expanded access programs (EAPs) provide medication to patients with life-threatening, treatment-refractory illnesses before regulatory approval and allow the acquisition of safety information. A 2-part, multisite EAP to evaluate abacavir, a carbocyclic nucleoside reverse-transcriptase inhibitor for use in combination antiretroviral therapy, was conducted. The EAP involved >13,000 adults infected with human immunodeficiency virus type 1 (HIV-1) who no longer responded to commercially available treatment regimens. Part A (open-label trials) examined the efficacy, safety, and tolerance of abacavir, and part B (provision of abacavir through expanded access) assessed only the occurrence of serious adverse events. By month 2 of abacavir-containing treatment, plasma HIV-1 RNA levels decreased by > or =0.5 log(10) in 31.4% of patients, and 5.6% of the patients had HIV-1 RNA levels decrease to <400 copies/mL. Drug-related serious adverse events were reported by 7.7% of patients, the most common of which were nausea, skin rash, diarrhea, malaise or fatigue, and fever. Approximately 4.6% of patients experienced a hypersensitivity reaction that was possibly drug related. Overall, the types and incidences of adverse events reported in the abacavir EAP were similar to those reported in phase 2 and 3 clinical trials evaluating abacavir.

Antiretroviral monotherapy for initial drug characterization risks the selection of resistant virus, yet monotherapy is the only setting where many fundamental properties of a new drug can be reliably determined. Using data on viral replication kinetics and dynamics, we designed an accelerated (14 day) open-label study of single agent emtricitabine (formerly known as FTC)--a nucleoside reverse transcriptase inhibitor--to select a dosing regimen for further therapeutic study. Five regimens (25 mg bd, 100 mg od, 200 mg od, 100 mg bd and 200 mg bd) were evaluated in HIV-1-infected subjects over a 14 day dosing period to determine the optimal dose and pharmacokinetics. Serial blood samples for virological, pharmacokinetic and intracellular FTC-triphosphate measurements were drawn frequently. A dose-response relationship for the antiviral activity of emtricitabine was established, with total daily doses of 200 mg or more producing the greatest median HIV-1 viral load suppression: 1.72-1.92 log10. Based on virological outcomes, dose-response analysis and intracellular triphosphate levels, a once-daily dose of 200 mg was selected for further long-term clinical study. Adverse events possibly related to emtricitabine were unremarkable. The antiviral activity of emtricitabine correlated well with intracellular FTC-triphosphate concentrations. This study design is a safe, useful tool for early dose selection for drugs with potent antiretroviral activity and linear pharmacokinetics.

We have undertaken a large-scale study of various tissues from normal controls and patients with Kaposi's sarcoma (KS) or other malignancies, both with and without human immunodeficiency virus infection, to determine the prevalence of human herpesvirus 8 (HHV-8) DNA. A total of 566 specimens were analyzed by PCR for the presence of HHV-8 DNA. Of the samples tested, 251 were obtained from patients with KS and 315 were obtained from patients without KS. HHV-8 DNA was detected in 103 (41%) of the 251 samples from patients with KS. In particular, 92% of KS tumor specimens were positive. None of the tissues from patients without KS showed evidence of HHV-8 DNA. Sequencing and phylogenetic analyses indicate a high degree of conservation (97.5 to 100%) among the HHV-8 strains tested.

Thirty-four subjects with symptomatic HIV-1 infection, p24 antigenaemia, and CD4 cell counts > 200/mm3 were randomly assigned to receive treatment with either zidovudine (ZDV) orally, interferon-alpha (IFN-alpha) subcutaneously, or both at respective low (200 mg ZDV/ 2 million international units IFN-alpha (MIU)), middle (400 mg/4 MIU) or high (600 mg/6 MIU) daily dose levels for 12 weeks. Thereafter, all patients received combination therapy at the initially assigned dose level to a total of 96 weeks. This design permitted analysis by the combination index (CI) method, which demonstrated antiretroviral synergy between ZDV and IFN-alpha with respect to p24 antigen suppression. Over the first 12 weeks, combination therapy was acceptably tolerated, more so than IFN-alpha monotherapy, and it was significantly more active in suppressing antigenaemia than either of the monotherapies. Similarly, the high-dose combination was the most active dose level over weeks 12 to 96. Combination ZDV/IFN-alpha at the optimal dose level defined by this trial merits further study. In addition, the CI design strategy employed here may be useful for the investigation of new antiretroviral combinations.

Objectives: To define the spectrum of HIV-1-related disease in New York City (NYC) and to determine how the clinical spectrum of illness differs in various populations., Design and Methods: The medical records of the 2983 HIV-infected individuals who had received care through 1989 at four hospital outpatient clinics and two private physicians' offices were reviewed retrospectively., Results: Sixty-one per cent of the study patients and 48% of patients seen in 1989 had AIDS. HIV-infected women were significantly less likely to have AIDS and CD4 lymphocyte counts less than 200 x 10(6)/l than men. For every 100 AIDS patients seen in 1989, there were 88 non-AIDS patients with CD4 counts less than 500 x 10(6)/l, of whom 41 had CD4 counts less than 200 x 10(6)/l; thus, in addition to an estimated 16,425 individuals living with AIDS in NYC, we estimate that there are at least 14,454 HIV-infected individuals without AIDS with CD4 counts less than 500 x 10(6)/l, of whom 6734 have CD4 counts less than 200 x 10(6)/l. Men who have sex with men were significantly more likely to have Kaposi's sarcoma, cytomegalovirus disease and retinitis, cryptosporidiosis and lymphoma, and significantly less likely to have Pneumocystis carinii pneumonia, esophageal candidiasis, extrapulmonary tuberculosis (TB) and bacterial pneumonia than intravenous drug users. Whites were significantly less likely to have pulmonary TB than Hispanics, non-Haitian and Haitian blacks, toxoplasmosis than Hispanics and Haitian blacks, and salmonella septicemia than non-Haitian blacks. The frequencies of most diagnoses did not differ by sex; gynecologic diseases were recorded infrequently in the medical records of women in this study., Conclusions: These data indicate that there are more than 30,000 HIV-infected adults living in NYC with significant immunosuppression, that an increasing proportion of AIDS cases in NYC will occur among women, and that the spectrum of HIV-related disease varies markedly in different populations.

Seroprevalence of human immunodeficiency virus type 1 (HIV-1) and human T lymphotropic virus types I and II (HTLV-I/II) was determined among 1160 intravenous (iv) drug abusers from five drug treatment or medical centers (Manhattan, Brooklyn, New Jersey, Detroit, and New Orleans). HIV-1 infection ranged from 5% in New Orleans to 48% in New York City. Hispanics and blacks had a significantly higher rate of HIV-1 infection than whites (P less than .01), but within each group rates were similar between males and females and by age stratum. HTLV-I/II seroprevalence increased with age from 3% in the 20-29 year age group to 37% in the group greater than 50 years. New Orleans and Manhattan (24%) had the highest rate, and blacks (19%) had a higher rate than either Hispanics (6.3%) or whites (7.3%). No association between HIV-1 and HTLV-I/II infection was observed except in Manhattan. When compared with iv drug abusers infected only with HIV-1, dually infected subjects had more clinical symptoms related to immune deficiency but a lower prevalence of HIV antigenemia. These data document the frequent occurrence of retroviral infections in iv drug abusers. The contrast between the two classes of virus suggests that HIV-1 is more efficiently transmitted, while the age-dependent rise in HTLV-I/II seroprevalence suggests cumulative exposure of a less-transmissible agent.

Human immunodeficiency virus, type 1 (HIV-1), produces a chronic infection with a long latency before clinical disease. We followed 214 untreated subjects for 12-42 months to study the natural history of HIV infection: 110 were classified as asymptomatic, 11 as AIDS-related complex (ARC), 15 as AIDS with Kaposi's sarcoma (KS), 31 as AIDS with opportunistic infections (AIDS/OI), and 47 were HIV-seronegative controls. The quantitative capacity of serum to complex HIV p24 antigen, termed the p24 binding capacity (p24 BC), and quantitative levels of HIV p24 antigen in serum were determined at regular intervals. For people in all diagnostic groups, a p24 BC below 31 ng/ml was more closely associated with progression to AIDS/OI than was p24 antigen positivity; 94% of AIDS/OI, 86% of ARC, 56% of AIDS/KS, and 19% of asymptomatic subjects had p24 BC less than 31 ng/ml during the study period, while 67% of AIDS/OI, 27% of ARC, 61% of AIDS/KS, and 20% of asymptomatic subjects were p24 antigenemic. Prospective analysis of 47 asymptomatic seropositive men followed for 3 years, who showed actuarial progression rates to ARC at 4%, 13%, and 23% and to AIDS at 5%, 8%, and 8% at 1, 2, and 3 years, indicated that entry levels of p24 BC below 31 ng/ml were as strongly associated with progression to ARC/AIDS as was p24 antigenemia (p = 0.0003 vs. p = 0.008). The p24 binding capacity assay is a new and convenient methodology to measure immunocomplexing antibody to HIV p24 and is a powerful indicator of progressive HIV disease.

Intravenous drug users are the second largest group to develop the acquired immunodeficiency syndrome, and they are the primary source for heterosexual and perinatal transmission in the United States and Europe. Understanding long-term trends in the spread of human immunodeficiency virus among intravenous drug users is critical to controlling the acquired immunodeficiency syndrome epidemic. Acquired immunodeficiency syndrome surveillance data and seroprevalence studies of drug treatment program entrants are used to trace seroprevalence trends among intravenous drug users in the borough of Manhattan. The virus entered this drug-using group during the mid-1970s and spread rapidly in 1979 through 1983. From 1984 through 1987, the seroprevalence rate stabilized between 55% and 60%--well below hepatitis B seroprevalence rates. This relatively constant rate is attributed to new infections, new seronegative persons beginning drug injection, seropositive persons leaving drug injection, and increasing conscious risk reduction. [ABSTRACT FROM AUTHOR]