The HIV care continuum among men who have sex with men in Moscow, Russia: a cross-sectional study of infection awareness and engagement in care.

OBJECTIVES: Early diagnosis and treatment of HIV infection is critical to improving clinical outcomes for HIV-infected individuals. We sought to characterise the HIV care continuum and identify correlates of being unaware of one's HIV infection among men who have sex with men (MSM) in Moscow, Russia. METHODS: Participants (N=1376) were recruited via respondent-driven sampling and completed a sociobehavioural survey and HIV testing from 2010 to 2013. Sample and population estimates were calculated for key steps along the HIV care continuum for HIV-infected MSM and logistic regression methods were used to examine correlates of being unaware of one's HIV infection. RESULTS: 15.6% (184/1177; population estimate: 11.6%; 95% CI 8.5% to 14.7%) of participants were HIV infected. Of these, only 23.4% (43/184; population estimate: 13.2; 95% CI 11.0 to 15.4) were previously aware of their infection, 8.7% (16/184 population estimate: 4.7; 95% CI 1.0 to 8.5) were on antiretroviral therapy (ART), and 4.4% (8/164; population estimate: 3.0; 95% CI 0.3 to 5.6) reported an undetectable viral load. Bisexual identity (reference: homosexual; adjusted odds ratio (AOR): 3.69; 95% CI 1.19 to 11.43), having ≥5 sexual partners in the last 6 months (reference: ≤1; AOR: 4.23; 95% CI 1.17 to 15.28), and employer HIV testing requirements (reference: no; AOR: 15.43; 95% CI 1.62 to 147.01) were associated with being unaware of one's HIV infection. HIV testing in a specialised facility (reference: private; AOR: 0.06; 95% CI 0.01 to 0.53) and testing ≥2 times in the last 12 months (reference: none; AOR: 0.17; 95% CI 0.04 to 0.73) were inversely associated with being unaware of HIV infection. CONCLUSIONS: There is a steep gradient along the HIV care continuum for Moscow-based MSM beginning with low awareness of HIV infection. Efforts that improve access to acceptable HIV testing strategies, such as alternative testing facilities, and linkage to care are needed for key populations.

Alcohol Use and Associated Sexual and Substance Use Behaviors Among Men Who Have Sex with Men in Moscow, Russia.

Alcohol use is a public health problem in the Russian Federation. This study explored relationships between alcohol use and behavioral risks for HIV transmission among men who have sex with men (MSM) in Moscow, Russia. Alcohol use disorder identification test (AUDIT) scores for 1367 MSM participating in a cross-sectional survey and HIV testing were categorized to: "abstinence/low use", "hazardous use", "harmful use/dependency". Multiple logistic regression models compared dependent variables for sexual and drug use behaviors across alcohol use strata. Hazardous and harmful/dependent alcohol use were significantly associated with high-risk sexual behaviors and drug use. Harmful use/dependency was associated with an increased odds of having more than five male sex partners (last 12 months; adjusted odds ratios-AOR 1.69; 95 % CI 1.25-2.27), inconsistent condom use during anal intercourse (AOR 2.19; 95 % CI 1.61-2.96) and, among those using recreational drugs, injection drug use (last month; AOR 4.38: 95 % CI 1.13-17.07) compared to abstinent/low-level users. Harmful/dependent use was marginally associated with HIV infection (AOR 1.48; 95 % CI 0.97-2.25). HIV prevention efforts for MSM in Moscow may benefit from addressing problem alcohol use to mitigate high-risk behaviors.

Anal human papillomavirus and HIV: A cross-sectional study among men who have sex with men in Moscow, Russia, 2012-2013.

Anal human papillomavirus (HPV) is prevalent among men who have sex with men (MSM), but has not been studied in the Russian Federation. A cross-sectional survey and HPV genotyping were conducted among HIV seropositive (n=58) and seronegative MSM (n=65)in Moscow. Multivariable logistic regression was performed to identify correlates of infection with oncogenic HPV genotypes 16 and/or 18 (HPV 16/18). Forty per cent (49/124) of all MSM were infected with at least one anal HPV genotype, 31.5% (39/124) had HPV16/18,and 11.5% (14/121) had high-grade squamous intraepithelial lesions (HSIL). HPV 16/18 was more prevalent in HIV seropositive than seronegative men (24/58,41.4% vs 15/65, 23.1%; p=0.03). HIV infection was independently associated with HPV 16/18 (adjusted odds ratio (AOR): 5.08; 95% confidence intervals (CI):1.49-17.34, p=0.01), as was having 2-4 steady male sex partners in the last year (vs ≤ 1 partner; AOR: 6.99;95%CI: 1.94­25.24, p<0.01). History of prison/detention,migration to/within Russia and use of incompatible lubricants were marginally associated with HPV16/18 (p<0.10). Comprehensive prevention options are needed to address HIV and HPV infection among MSM in Russia and may benefit from inclusion of young men in piloted HPV vaccination programmes.

Social and structural risks for HIV among migrant and immigrant men who have sex with men in Moscow, Russia: implications for prevention.

Moscow has a large population of immigrants and migrants from across the Former Soviet Union. Little is studied about men who have sex with men (MSM) within these groups. Qualitative research methods were used to explore identities, practices, and factors affecting HIV prevention and risks among immigrant/migrant MSM in Moscow. Nine interviews and three focus group discussions were conducted between April-June 2010 with immigrant/migrant MSM, analyzed as a subset of a larger population of MSM who participated in qualitative research (n=121). Participants were purposively selected men who reported same sex practices (last 12 months). Migrants were men residing in Moscow but from other Russian regions and immigrants from countries outside of Russia. A socioecological framework was used to describe distal to proximal factors that influenced risks for HIV acquisition. MSM ranged from heterosexual to gay-identified. Stigma and violence related to homophobia in homelands and concerns about xenophobia and distrust of migrants in Moscow were emerged as key themes. Participants reported greater sexual freedom in Moscow but feared relatives in homelands would learn of behaviors in Moscow, often avoiding members of their own ethnicity in Moscow. Internalized homophobia was prevalent and linked to traditional sexual views. Sexual risks included sex work, high numbers of partners, and inconsistent condom use. Avoidance of HIV testing or purchasing false results was related to reporting requirements in Russia, which may bar entry or expel those testing positive. HIV prevention for MSM should consider immigrant/migrant populations, the range of sexual identities, and risk factors among these men. The willingness of some men to socialize with immigrants/migrants of other countries may provide opportunities for peer-based prevention approaches. Immigrants/migrants comprised important proportions of the MSM population, yet are rarely acknowledged in research. Understanding their risks and how to reach them may improve the overall impact of prevention for MSM and adults in Russia.

Failure of T-cell homeostasis preceding AIDS in HIV-1 infection. The Multicenter AIDS Cohort Study.

We and others have postulated that a constant number of T lymphocytes is normally maintained without regard to CD4+ or CD8+ phenotype ('blind' T-cell homeostasis). Here we confirm essentially constant T-cell levels (despite marked decline in CD4+ T cells and increase in CD8+ T cells) in homosexual men with incident human immunodeficiency virus, type 1 (HIV-1), infection who remained free of acquired immunodeficiency syndrome (AIDS) for up to eight years after seroconversion. In contrast, seroconverters who developed AIDS exhibited rapidly declining T cells (both CD4+ and CD8+) for approximately two years before AIDS, independent of the time between seroconversion and AIDS, suggesting that homeostasis failure is an important landmark in HIV disease progression. Given the high rate of T-cell turnover in HIV-1 infection, blind T-cell homeostasis may contribute to HIV pathogenesis through a CD8+ T lymphocytosis that interferes with regeneration of lost CD4+ T cells.

An evaluation of assumptions underlying respondent-driven sampling and the social contexts of sexual and gender minority youth participating in HIV clinical trials in the United States.

INTRODUCTION: Respondent-driven sampling has been an effective sampling strategy for HIV research in many settings, but has had limited success among some youth in the United States. We evaluated a modified RDS approach for sampling Black and Latinx sexual and gender minority youth (BLSGMY) and evaluates how lived experiences and social contexts of BLSGMY youth may impact traditional RDS assumptions. METHODS: RDS was implemented in three cities to engage BLSGMY in HIV prevention or care intervention trials. RDS was modified to include targeted seed recruitment from venues, internet, and health clinics, and provided options for electronic or paper coupons. Qualitative interviews were conducted among a sub-sample of RDS participants to explore their experiences with RDS. Interviews were coded using RDS assumptions as an analytic framework. RESULTS: Between August 2017 and October 2019, 405 participants were enrolled, 1,670 coupons were distributed, with 133 returned, yielding a 0.079 return rate. The maximum recruitment depth was 4 waves among seeds that propagated. Self-reported median network size was 5 (IQR 2-10) and reduced to 3 (IQR 1-5) when asked how many peers were seen in the past 30 days. Qualitative interviews (n=27) revealed that small social networks, peer trust, and targeted referral of peers with certain characteristics challenged network, random recruitment, and reciprocity assumptions of RDS. HIV stigma and research hesitancy were barriers to participation and peer referral. CONCLUSIONS: Small social networks and varying relationships with peers among BLSGMY challenge assumptions that underlie traditional RDS. Modified RDS approaches, including those that incorporate social media, may support recruitment for community-based research but may challenge assumptions of reciprocal relationships. Research hesitancy and situational barriers must be addressed in recruitment and study designs.

Impact of pooling on accuracy of hepatitis B virus surface antigen screening of blood donations.

Expenditure on screening blood donations in developing countries can be reduced by testing donations in pools. This study evaluated serological screening in pools for hepatitis B virus (HBV) at the Israeli national blood bank and a hospital blood bank in Gaza, the Palestinian Authority. The accuracy of HBV surface antigen (HBsAg) enzyme immunoassay performed on pools of 3-24 samples was compared with individual tests. Delay in detecting positive samples due to dilution in pools and the possibility of antibody-antigen neutralization were analyzed. The sensitivity of pooled testing for HBsAg was 93-99%, prolonging the window period by 5 days (8.3%). Neutralization of HBsAg by hepatitis B surface antibodies (anti-HBs) could be minimized by testing immediately after pooling. Serological testing for HBsAg in pools may be performed using manually created pools of up to six samples, with 5% loss in sensitivity and a risk of neutralization by anti-HBs present in the donor population. Pooling can therefore be considered as an option only in countries with a low prevalence of HBV.

Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy.

Helminthic parasites cause widespread, persistent infections in humans. The immigration of Ethiopians to Israel (a group denoted here by "Eth."), many of them infested with helminths and in a chronic immune-activation state, enabled us to investigate the effects of such immune activation on immune responses. We studied the immune profile and immune functions of 190 Eth. and Israeli non-Eth. (Isr.) highly, partially, or non-immune-activated individuals. Immune cells from highly immune-activated individuals were defective in several signaling responses, all of which were restored gradually following anti-helminthic treatment. These cells showed poor transmembrane signaling, as seen by the phosphorylation of various tyrosine kinases and of the MAPK kinases, ERK1/2 and p38; deficient degradation of phosphorylated IkappaBalpha; increased expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), which appears to block proliferative responses in these cells; decreased beta-chemokine secretion by CD8(+) cells after stimulation; and reduced proliferation to recall antigen stimulation. Highly immune-activated individuals also showed decreased delayed-type skin hypersensitivity responses to recall antigen before deworming. These findings support the notion that chronic helminthic infections cause persistent immune activation that results in hyporesponsiveness and anergy. Such impaired immune functions may diminish the capacity of these individuals to cope with infections and to generate cellular protective immunity after vaccination.

Estimation of delay in detecting hepatitis C virus antibodies in pools compared to individual testing on seroconversion panels.

Testing for anti-hepatitis C virus (HCV) antibodies in pools may reduce blood screening costs, making this approach affordable for developing countries, provided that the dilution of infected blood does not significantly increase the number of undetectable viral particles, especially in seroconverters. This study assessed the delay in detection of HCV antibodies in five HCV seroconversion panels, tested in pools of 6-48 samples, and estimated the risk of transfusion-transmitted HCV caused by pooling. The delay in detection of positive samples was 5-12 days for pools of all sizes, adding 7% to the risk of HCV transmission that occurs when blood donors' samples are tested individually.

Risk factors for methadone outside treatment programs: implications for HIV treatment among injection drug users.

BACKGROUND: Diversion of methadone outside treatment programs occurs, yet reasons for use of 'street methadone' are characterized poorly. Self-medication for withdrawal symptoms is one plausible hypothesis. Among HIV-infected drug users, some antiretroviral medications can reduce potency of methadone, yet any association between such effects and the use of supplemental methadone sources remains undetermined. OBJECTIVE: To estimate the frequency and risk factors for use of street methadone. METHODS: Injection drug users (IDUs) recruited through extensive community outreach in 1988-89 and 1994 were followed semi-annually with questionnaires about health history, use of licit and illicit drugs including methadone and HIV-related assays. Analyses were performed using generalized estimating equation logistic regression. RESULTS: Of 2811 IDUs enrolled and eligible for analysis, 493 people reported use of street methadone over 12 316 person-years of follow-up (4.0/100 person-years). In multivariate analyses, street methadone use was more common among women, whites, those 40-59 years old, those who reported withdrawal symptoms, past methadone program attendance (6-12 months before visit), recent heroin injection with or without cocaine (but not cocaine alone), smoking or sniffing heroin and reported trading sex. Street methadone was not associated with HIV infection or treatment. CONCLUSION: The results suggest that older IDUs still using heroin may be using street methadone to treat signs of withdrawal. The absence of a higher rate of street methadone use in HIV seropositive IDUs reveals that antiretroviral/methadone interactions are not a primary determinant of use outside of treatment settings.

Increased risk of bloodstream and urinary infections in intensive care unit (ICU) patients compared with patients fitting ICU admission criteria treated in regular wards.

Critically ill patients, eligible for admission into intensive care units (ICUs), are often hospitalized in other wards due to a lack of ICU beds. Differences in morbidity between patients managed in ICUs and elsewhere are unknown, specifically the morbidity related to hospital-acquired infection. Patients fitting ICU admission criteria were identified by screening five entire hospitals on four separate days. Hospital infections within a 30-day follow-up period were compared in ICU patients and in patients on other wards using Kaplan-Meier curves. Residual differences in the patients' case mix between ICUs and other wards were adjusted for utilizing multivariate Cox models. Of 13415 patients screened, 668 were critically ill. The overall infection rates (per 100 patient-days) were 1.2 for bloodstream infection (BSI) and 1.9 for urinary tract infection (UTI). The adjusted hazard ratios in ICU patients compared with patients on regular wards were 3.1 (P<0.001) for BSI and 2.5 (P<0.001) for UTI. This increased risk persisted even after adjusting for the disparity in the number of cultures sent from ICUs compared with ordinary wards. No interdepartmental differences were found in the rates of pneumonia, surgical wound infections and other infections. Minimizing the differences between characteristics of patients hospitalized in ICUs and in other wards, and controlling for the higher frequency of cultures sent from ICUs did not eliminate the increased risk of BSI and UTI associated with admission into ICUs.

Comparison of clinical symptoms of human immunodeficiency virus disease between intravenous drug users and homosexual men.

BACKGROUND: To compare the prevalence of human immunodeficiency virus (HIV)-related clinical symptoms among male intravenous drug users and homosexual men stratified by HIV serostatus and CD4 cell levels. METHODS: A cross-sectional sample using concurrent longitudinal studies of the natural history of HIV-1 infection among intravenous drug users (N = 539) and homosexual men (N = 932) was recruited in Baltimore, Md. Participants were administered a risk behavior interview and physical examination, and had hematologic tests evaluated in a similar calendar period. RESULTS: Both risk groups demonstrated an inverse relationship between frequency of symptoms and CD4 cell count. Fever, night sweats, and lymphadenopathy were not evaluated because pilot data suggested a confounding association with drug injection. Among those with mild to moderate immune suppression, intravenous drug users were significantly more likely than homosexual men to experience fatigue, weight loss, diarrhea, and shortness of breath; to have oral candidiasis, palpable spleen, and lower mean weight on physical examination; and abnormal hematocrit, platelets, and total lymphocyte counts. However, participants in either risk group with CD4 cell levels below 0.2 x 10(9)/L experienced similar frequency of all clinical symptoms. Self-reported oral candidiasis increased fourfold with HIV infection and was as likely in both groups at all CD4 cell levels. Duration and recency of intravenous drug use was not significantly associated with the higher frequency of most clinical symptoms. CONCLUSION: Social factors are an important consideration in evaluating the association between clinical symptoms and HIV immunosuppression. Except for oral candidiasis, there are limitations for the use of clinical symptoms as intermediate outcome measures for HIV infection among intravenous drug users.

Instability of delayed-type hypersensitivity skin test anergy in human immunodeficiency virus infection.

OBJECTIVE: To evaluate stability of delayed-type hypersensitivity (DTH) skin test over time in human immunodeficiency virus (HIV)-seropositive and HIV-seronegative injecting drug users. METHOD: A community-based cohort of injecting drug users who had serial skin testing with purified protein derivative tuberculin, mumps, and Candida albicans antigen. Delayed-type hypersensitivity anergy was defined as a skin test result of less than 3 mm for all three antigens; DTH positivity was a skin test result of 3 mm or greater for at least one antigen (Centers for Disease Control and Prevention, Atlanta, Ga, 1993). RESULTS: At baseline, 36% of HIV-seropositive subjects (n = 401) were anergic as compared with 14% of HIV-seronegative subjects (n = 552; P < .001). During follow-up, fewer HIV-seropositive subjects remained DTH positive (42%) and more remained anergic (19%) than of HIV-seronegative subjects (67% and 7%, respectively). Twenty-four percent of HIV-seropositive subjects who were initially DTH positive became anergic as compared with 15.3% of the HIV-seronegative subjects. However, the proportion changing from anergy to DTH positivity was greater among HIV-seropositive subjects (15%) than HIV-seronegative subjects (12%). In comparison to those who remained DTH positive, HIV-seropositive subjects with CD4 cell counts of less than 0.50 x 10(9)/L (odds ratio = 6.4) and less than 0.35 x 10(9)/L (odds ratio = 11.2) were more likely to remain anergic than those who had CD4 cell counts above 0.50 x 10(9)/L or were HIV seronegative. CONCLUSIONS: Although the prevalence and incidence of DTH anergy were higher in HIV-seropositive subjects, high rates of change in DTH status occurred in both directions. This suggests that instability of DTH skin testing is substantial and only partially dependent on HIV status. Although a single test may be an unreliable indicator of HIV-induced immunosuppression, two consecutive anergic readings were strongly associated with a CD4 cell count below 0.50 x 10(9)/L and particularly below 0.35 x 10(9)/L. For determining false negativity of tuberculin tests, persistent DTH anergy is more reliable than a single test among HIV-seropositive injecting drug users. Anergy testing appears to be unnecessary with CD4 cell counts greater than 0.5 x 10(9)/L.

Effect of isoniazid chemoprophylaxis on HIV-related mycobacterial disease.

OBJECTIVES: The aims of this study were to (1) identify trends and risk factors for mycobacterial disease and (2) determine the effect of expanded access to isoniazid chemoprophylaxis on tuberculosis incidence. METHODS: A prospective observational cohort study was conducted among community-based injecting drug users (IDUs); 2960 IDUs (942 human immunodeficiency virus [HIV] seropositive) were followed up from January 1988 to June 1994. Directly observed chemoprophylaxis with twice-weekly isoniazid (10 to 15 mg/kg) was offered to purified protein derivative (PPD) tuberculin-positive (> or = 5-mm induration diameter in HIV-seropositive subjects and > or = 10-mm diameter in HIV-seronegative subjects) individuals but not to those with cutaneous anergy. Overall and annual incidence rates of disease due Mycobacterium tuberculosis, Mycobacterium avium complex, and other atypical mycobacteria were estimated using Poisson regression. RESULTS: HIV seropositivity was the strongest risk factor for tuberculosis, M avium complex, and other mycobacterial disease (relative risk [RR], 3.8, 17.2, and 6.9, respectively). Median CD4 lymphocyte cell counts for the three groups of mycobacterial disease were 0.17, 0.03, and 0.02 x 10(9)/L (167/microL, 30/microL, 18/microL) within 6 months of diagnosis (before or after). Overall incidence rates of tuberculosis, M avium complex disease, and other mycobacterial disease were 1.9, 8.8, and 2.7 per 1000 person-years, respectively. Tuberculosis incidence peaked in 1991 at six per 1000 person-years. However, after access to directly observed preventive therapy was expanded for tuberculin-positive subjects, incidence fell to only one case in 1992 and zero cases for 24 months from mid-1992 to mid-1994. During this period the number of PPD-positive patients who completed at least 26 weeks of therapy (or were still receiving isoniazid) more than tripled (from 21 to 70). None of the 12 patients with tuberculosis diagnosed during follow-up had received any preventive therapy. In addition, no tuberculosis developed among participants with cutaneous anergy. Calendar trends in risk for M avium complex and tuberculosis diverged after expanded access to isoniazid prophylaxis. Compared with 1988-1989, risk of M avium complex increased sevenfold. Tuberculosis risk fell 83% from the peak risk in 1990-1991. CONCLUSIONS: Expanded access to directly observed isonazid therapy for tuberculin-positive IDUs with and without HIV infection was associated with an 83% drop in tuberculosis incidence, while in the same period M avium complex incidence significantly increased. These population-based data are consistent with those obtained from clinical trials of isoniazid prophylaxis and were obtained without offering chemoprophylaxis to HIV-infected patients with cutaneous energy.

Sex differences in risk factors for hiv seroconversion among injection drug users: a 10-year perspective.

BACKGROUND: Injection drug use directly or indirectly accounts for nearly half the annual human immunodeficiency virus (HIV) infections in the United States. Prospective studies that investigate both sexual and parenteral HIV risks among injection drug users (IDUs) are needed. We studied factors for HIV seroconversion among male and female IDUs in Baltimore, Md. METHODS: The HIV-negative IDUs (1447 male and 427 female) were recruited into a prospective study from 1988 to 1989 or in 1994. Participants underwent semiannual HIV tests and surveys through December 1998. Poisson regression was used to identify risk factors for HIV seroconversion, stratified by sex. Behaviors were treated as time-dependent covariates that varied at each semiannual period. RESULTS: Subjects were primarily African American (91%), and median age at enrollment was 35 years. Incidence of HIV was 3.14 per 100 person years (95% confidence interval, 2.78-3.53) and did not significantly differ by sex. Younger age independently predicted HIV seroconversion for both men and women. Among men, factors that independently predicted HIV seroconversion were the following: less than a high school education, recent needle sharing with multiple partners, daily injection, and shooting-gallery attendance. The incidence of HIV was double for men recently engaging in homosexual activity and cocaine injection. Among women, the incidence of HIV was more than double for those recently reporting sexually transmitted diseases. CONCLUSIONS: The incidence of HIV remained high among IDUs in Baltimore over the past decade. Risk factors for HIV seroconversion differed markedly by sex. Predominant risks among men included needle sharing and homosexual activity; among women, factors consistent with high-risk heterosexual activity were more significant than drug-related risks. Human immunodeficiency virus interventions aimed at IDUs should be sex-specific and incorporate sexual risks.

HIV incidence among repeat HIV testers with sexually transmitted diseases in Italy. STD Surveillance Working Group.

OBJECTIVES: To provide data on the incidence of HIV infection among repeat testers with sexually transmitted diseases (STD) in Italy. DESIGN: Retrospective longitudinal study. METHODS: Study participants, enrolled by 47 STD centres throughout Italy, included individuals with a newly diagnosed STD who were tested for HIV at the time of the STD diagnosis and who had a previous documented HIV-negative test. 'Seroconverters' were defined as those individuals who tested HIV-positive at the time of the STD diagnosis. The cumulative and the annual incidence of HIV in this population were estimated. RESULTS: Of 1950 patients, 47 were seroconverters, with an incidence rate of 1.7 per 100 person-years (PY) (95% confidence interval, 1.2-2.2). HIV incidence was higher among males than among females (2.5 versus 0.6 per 100 PY). The highest incidence rate was found among homosexual injecting drug users (IDU) (13.8 per 100 PY), whereas the lowest rate was observed among heterosexual non-IDU (0.4 per 100 PY). The annual incidence decreased from 1.8 per 100 PY in 1989 to 0.9 per 100 PY in 1996. CONCLUSIONS: Our results show that new HIV infections have occurred among STD patients in Italy since 1988, although a clear decrease in incidence has occurred since 1989. However, the rate of seroconversion appears to be alarmingly high in some high-risk groups. These findings suggest that there is a need for continued monitoring of new HIV infections among STD patients, and these individuals may represent a useful sentinel population for a better understanding of the HIV epidemic.

Comparison of clinical manifestations of HIV infection between male and female injecting drug users.

OBJECTIVE: To compare occurrence of clinical symptoms, physical examination findings and hematologic variables in male and female HIV-seropositive injecting drug users (IDU) with similar CD4+ lymphocyte counts. METHOD: We interviewed and examined 118 female and 444 male AIDS-free HIV-seropositive IDU for clinical signs and symptoms. HIV serology and T-lymphocyte subset evaluations were performed. Comparisons were analyzed by Mantel-Haenszel procedures. RESULTS: In this population, median age for men was 35 years versus 33 years for women; median CD4 cell count was 490 x 10(6)/l for men versus 480 x 10(6)/l for women. The overall frequency of oral candidiasis increased as CD4 cell count decreased, but did not vary by sex. Recent history of genital herpes was more frequent (P < 0.05) in women than men, but this difference was not significant on physical examination. Symptoms of diarrhea, fatigue, weight loss, shortness of breath, presence of enlarged posterior cervical lymph nodes did not vary by CD4 cell count or sex, and no strong interactions were evident. Although absolute values of hematocrit were higher (P < 0.001) and platelet count lower (P < 0.001) in HIV-seropositive men than women, distributions of hematocrit and platelet count by sex were similar for HIV-seropositive participants and HIV-seronegative controls. CONCLUSION: Our data on IDU prior to a diagnosis of AIDS suggest that constitutional signs and symptoms are generally similar among men and women early in HIV infection. Additional follow-up is needed to determine whether differential rates of signs and symptoms by sex appear with progression of HIV infection.

Clinical characteristics and prognostic value of acute retroviral syndrome among injecting drug users. Italian Seroconversion Study.

OBJECTIVE: To estimate the frequency of acute retroviral syndrome associated with HIV infection among injecting drug users (IDU), and to determine the extent to which acute retroviral syndrome predicts a faster rate of progression to AIDS and immunosuppression in this population. DESIGN: Prospective study of HIV seroconverters (median follow-up, 50.5 months). SETTING: Sixteen clinical centres throughout Italy established to study the natural history of HIV infection. PATIENTS: Three hundred and ninety-one IDU for whom the date of HIV seroconversion was established with a 9-month precision. MAIN OUTCOME MEASURES AND METHODS: Incidence of acute retroviral syndrome with signs and symptoms that included fever (temperature > 38 degrees C) occurring within 6 months prior to the time of first positive HIV test, progression to AIDS, crude and adjusted relative hazard of AIDS using survival analysis techniques, and trajectories of CD4+ cell counts using a piece-wise linear regression model incorporating the degree of dependency of within-person measurements. RESULTS: Of 391 HIV seroconverters, 39 (10.0%) were diagnosed with acute retroviral syndrome. During follow-up, 13 seroconverters with acute retroviral syndrome and 24 asymptomatic seroconverters developed AIDS. The Kaplan-Meier estimates for the cumulative AIDS incidence during 4.5 years of follow-up were 26.8 and 6.5%, respectively; the relative hazard of developing AIDS for acute retroviral syndrome was 5.59 (95% confidence interval, 2.79-11.20) after adjustment for age, sex and year of seroconversion. Although CD4+ level within the first year from seroconversion was similar, the rate of CD4+ cell decline after 1 year from seroconversion was faster in individuals with acute retroviral syndrome than in those without this syndrome (P < 0.001). CONCLUSIONS: Among HIV-infected IDU, a distinct acute retroviral syndrome is apparent and associated with a faster rate of clinical progression to AIDS and HIV-related immunosuppression.

Time to initiating highly active antiretroviral therapy among HIV-infected injection drug users.

OBJECTIVE: Studies have shown that HIV-infected injection drug users (IDUs) are less likely to receive antiretroviral therapy than non-drug users. We assess factors associated with initiating highly active antiretroviral therapy (HAART) in HIV-infected IDUs. METHODS: A cohort study of IDUs carried out between 1 January 1996 and 30 June 1999 at a community-based study clinic affiliated to the Johns Hopkins University, Baltimore, Maryland. The participants were a total of 528 HIV-infected IDUs eligible for HAART based on CD4+ cell count. The main outcome measure was the time from treatment eligibility to first self-reported HAART use, as defined by the International AIDS Society-USA panel (IAS-USA) guidelines. RESULTS: By 30 June 1999, 58.5% of participants had initiated HAART, most of whom switched from mono- or dual-combination therapy to a HAART regimen. Nearly one-third of treatment-eligible IDUs never received antiretroviral therapy. Cox proportional hazards regression showed that initiating HAART was independently associated with not injecting drugs, methadone treatment among men, having health insurance and a regular source of care, lower CD4+ cell count and a history of antiretroviral therapy. CONCLUSIONS: Self-reported initiation of HAART is steadily increasing among IDUs who are eligible for treatment; however, a large proportion continues to use non-HAART regimens and many remain treatment-naive. Although both groups appear to have lower health care access and utilization, IDUs without a history of antiretroviral therapy use would have more treatment options available to them once they become engaged in HIV care.

Markers of response to zidovudine monotherapy among treated HIV seroconverters. Italian Seroconversion Study.

The aim of the study was to evaluate indicators of response to zidovudine monotherapy in terms of progression to AIDS and death in a cohort of human immunodeficiency virus (HIV) seroconverters. From a larger observational epidemiological cohort of 1,024 HIV seroconverters we identified 315 persons on zidovudine monotherapy. In this treated cohort, age, sex, risk group, constitutional symptoms, CD4 cell count, and p24 antigen levels at initiation of treatment and 6 months later were examined separately for two outcomes, AIDS and death, using standard survival methods. The variables measured at the visit at which zidovudine monotherapy was initiated that predicted more rapid progression to AIDS were CD4 cell count (RH = 2.61); constitutional symptoms (RH = 2.56); p24 antigenaemia level (RH = 2. 17); and subsequent change in CD4 cell count (> 30% decline) contributed additional predictive information (RH = 2.70). Results were similar for mortality, and did not vary significantly by risk group. In a tested subset of patients, p24 antigenaemia was associated with high levels of plasma RNA viral load. The median number of HIV RNA copies was about 28,000 copies/ml among p24 antigen-positive individuals and about 7,700 copies/ml among participants who were persistently negative for p24 antigenaemia. CD4 cell count, symptoms and p24 antigenaemia at the start of therapy and CD4 cell decline after initiation of treatment are early indicators of disease progression in zidovudine-treated patients. The combined use of these indicators may help to better predict who will respond to zidovudine or to other antiretroviral therapies.