Showing papers in "Journal of Acquired Immune Deficiency Syndromes in 2001"

Self-reported symptoms and medication side effects influence adherence to highly active antiretroviral therapy in persons with HIV infection.

Abstract: Objectives To identify variables predictive of nonadherence to highly active antiretroviral therapy (HAART) and to assess whether self-reported symptoms or medication side effects are related to adherence. Design Cross-sectional multicenter study Adherence Italian Cohort Naive Antiretrovirals [AdICONA] within the Italian Cohort Naive Antiretrovirals (ICONA). Methods Participants receiving HAART completed a 16-item self-administered questionnaire to assess nonadherence in the last 3 days as well as the type and intensity of 24 common HIV- and HAART-related symptoms experienced during the last 4 weeks. Results From May 1999 to March 2000, 358 persons were enrolled: 22% reported nonadherence and were less likely to have HIV RNA Conclusions In addition to patient characteristics, medication-related variables, and reasons for nonadherence, patient-reported symptoms and medication side effects were significantly associated with adherence to HAART.

Trust and the acceptance of and adherence to antiretroviral therapy.

Abstract: BACKGROUND Antiretroviral therapy (ART) has resulted in reduced AIDS incidence and mortality. Socially marginalized individuals with HIV infection, particularly injection drug users (IDUs), have received less ART and derived less benefit than others. Little is known about the therapeutic process necessary to promote acceptance of and adherence to ART among marginalized HIV-infected populations. We report on the correlates of both acceptance of and adherence to ART among HIV infected prisoners, most of whom are IDUs. DESIGN Using a cross-sectional survey design within four ambulatory prison HIV clinics, 205 HIV-infected prisoners eligible for ART were recruited between March and October 1996. MEASUREMENTS Detailed interviews were conducted that included personal characteristics, health status and beliefs, and validated standardized scales measuring depression, health locus of control, social desirability and trust in physician, medical institutions and society. Acceptance and adherence were documented by self-report and validated for a subset by pharmacy review. Clinical information was obtained from standardized chart review. Adherence was defined as having taken > or = 80% of ART. RESULTS The acceptance of (80%) and adherence to (84%) ART among this group of prisoners was high. Multiple regression models demonstrated that correlates of acceptance of and adherence to ART differed. Acceptance was associated with trust in physician (8% increase for each unit increase with trust in physician scale) and trust in HIV medications (threefold reduction for those mistrustful of medication). Side effects (OR = 0.09), social isolation (OR = 0.08), and complexity of the antiretroviral regimen (OR = 0.33) were associated with decreased adherence. The prevalence of health beliefs suggesting an adverse relationship between ART and drugs of abuse was high (range 59 to 77%). Adherence did not differ among those receiving directly observed therapy (82%) or self-administration (85%). CONCLUSIONS ART can be successfully administered within a correctional setting. Trust and the therapeutic relationship between patient and physician remain central in the ART initiation process. Characteristics of the therapeutic agents and the degree of social isolation predict adherence. These results may inform the design of interventions to improve both acceptance of and adherence to ART particularly among marginalized populations who have not derived full benefit from these potent new therapies.

Detrimental effects of continued illicit drug use on the treatment of HIV-1 infection.

Abstract: Objective: To identify the effects of substance abuse status (active, former, and never) on utilization of highly active antiretroviral therapy (HAART), medication adherence, and virologic and immunologic responses to therapy. Design: Prospective cohort study of 764 HIV-1-infected patients who attended an urban HIV clinic and participated in a standardized interview. Main Outcome Measures: Past utilization of HAART, self-reported nonadherence with antiretroviral therapy, and changes in HIV-1 RNA level and CD4 + lymphocyte count relative to prior peak and nadir, respectively. Results: Forty-four percent of active drug users failed to utilize HAART compared with 22% of former drug users and 18% of non-drug users (p <.001 for both comparisons). Among participants who were taking antiretroviral therapy when interviewed, active drug users were more likely to report medication nonadherence (34% vs. 24% of nonusers and 17% of former users), had a smaller median reduction in HIV-1 RNA from baseline (0.8 log 10 copies/ml vs. 1.7 in nonusers and 1.6 in former users), and had smaller median increases in CD4 + lymphocyte count from baseline (65 cells/mm 3 vs. 116 in nonusers and 122 in former users) (p <.05 for all comparisons with active users). Conclusions: Active drug use was strongly associated with underutilization of HAART, nonadherence, and inferior virologic and immunologic responses to therapy, whereas former drug users and non-drug users were similar in all outcomes. Effective strategies are needed that integrate HIV-1 and substance abuse treatments.

Drug use and sexual risk behavior among gay and bisexual men who attend circuit parties: a venue-based comparison.

Abstract: Context: HIV risk behavior among urban gay/bisexual men has recently increased. High-risk sexual activity and drug use may be particularly high during circuit party (CP) weekends, during which gay/bisexual men congregate for social activities and dancing. Objectives: To compare prevalence of risk behaviors during CP weekends with those during non-CP weekends. Design: Cross-sectional study. Participants: 295 gay/bisexual men from the San Francisco Bay Area. Main Outcome Measures: Drug use and sexual risk behavior during a San Francisco CP weekend, a CP weekend held in another geographic area (distant weekends), and two non–CP weekends. Results: During their most recent distant CP weekend, 80% of participants used methylenedioxymethamphetamine (ecstasy), 66% ketamine, 43% crystal methamphetamines, 29% gamma-hydroxybutyrate or gamma-butyrolactone (GHB/GBL), 14% sildenafil (Viagra), and 12% amyl nitrites (poppers); 53% used four or more drugs. Drug use prevalence was greater during CP than non-CP weekends (p < .001). Unprotected anal sex with partners of unknown or opposite HIV serostatus was most prevalent during distant CP weekends, reported by 21% of HIV-positive and 9% of HIV-negative participants. In multivariate analysis, predictors of unprotected anal sex with opposite or unknown HIV serostatus partners included being HIV-positive (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4–7.5), and weekend use of crystal methamphetamines (OR 2.4; 95% CI, 1.1–4.9), sildenafil (OR, 3.8; 95% CI, 2.0–7.3), and amyl nitrites (OR, 2.2; 95% CI, 1.3–4.0). Conclusions: Prevalence of high-risk activity during these weekends suggests significant potential for HIV transmission in this population. Public health programs in communities hosting CPs should aim to reduce rates of drug use and sexual risk behavior among CP participants, especially HIV-positive men.

Determinants of heterogeneous adherence to HIV-antiretroviral therapies in the Multicenter AIDS Cohort Study.

Abstract: Assessment of adherence to HIV antiretroviral therapy (ART) is required for studying therapeutic effectiveness and identifying subgroups needing focused education. The study's goals were to describe the level of ART adherence using self-reported recall over a 4-day period and to characterize determinants of lower adherence. The interaction between adherence and drug holidays on level of HIV RNA also was investigated. Perfect self-reported adherence was defined as taking all doses and numbers of pills as prescribed for current HIV medications. Independent predictors of <100% adherence were determined using multivariate logistic regression. Among 539 men, 419 (77.7%) were 100% adherent by the algorithm using self-reported data. HIV-1 RNA was <50 copies/ml in 48.2% of the adherent group versus 33.7% in the less adherent group (p = .015). This proportion dropped to 28% if a drug holiday was reported in addition to lower adherence. A drug holiday was not virologically detrimental if the participant was otherwise adherent. Determinants of lower adherence included African American race (odds ratio [OR], 2.4; p = .008), income

Risk factors for severe hepatic injury after introduction of highly active antiretroviral therapy.

Abstract: Objectives Treatment of HIV infection with highly antiretroviral therapy (HAART) may be limited by liver toxicity. Its incidence and risk factors are not well known. Patients and methods Retrospective chart review. Naive patients beginning HAART between January 1997 and January 2000. Severe transaminase elevation was defined as fivefold or higher rise over upper normal limits, or as > or =3.5-fold rise above abnormal baseline values. Results Of 222 study subjects, 38%, 5%, and 2% were coinfected with hepatitis C virus (HCV), hepatitis B virus, and hepatitis D virus, respectively. Besides two nucleoside reverse transcriptase inhibitors (NRTIs), 96 patients received protease inhibitors (PIs), 90 received nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 35 received a PI + NNRTI combination. Severe hepatic injury developed in 21 (9%): 10% PI, 9%, and 9% PI + NNRTI. Both univariate and multivariate analyses identified alcohol abuse, HCV coinfection, and older age as independent risk factors. Predictor variables in the final multivariate model were: alcohol abuse (risk ratio [RR], 5.87; 95% confidence interval [CI], 1.49-23.15; p =.01], positive HCV serology (RR, 3.99; 95% CI, 1.32-12.10; p =.01], and older age (RR, 1.11; 95% CI, 1.04-1.18; p = 0.001). Conclusions Nearly 10% of study subjects who start HAART experience severe transaminase elevation, irrespective of the treatment. Avoidance of alcohol abuse, especially in study subjects coinfected with HCV, will reduce the risk of hepatic injury after HAART. When possible, prior treatment for chronic HCV infection should be considered.

Antiretroviral regimen complexity, self-reported adherence, and HIV patients' understanding of their regimens: survey of women in the her study.

Abstract: BACKGROUND: Research regarding treatment adherence in chronic diseases, such as hypertension, suggests that increasing complexity in the medication regimen is associated with decreasing patient adherence. However, less is known about the relationship between regimen complexity and adherence in the treatment of HIV/AIDS. OBJECTIVE: To examine the relationship between antiretroviral (ART) regimen complexity and patient understanding of correct regimen dosing to adherence (missing doses in the past 1 and 3 days). METHODS: Cross-sectional survey of a cohort of women living with HIV/AIDS and enrolled in the HER (HIV Epidemiologic Research) Study. RESULTS: Seventy-five percent of patients correctly understood the dosing frequency of their ART medications, 80% understood the food-dosing restrictions, whereas only 63% understood both. The percentage of patients with a correct understanding of dosing decreased with increasing regimen complexity (increased dosing frequency and food-dosing restrictions). Patients were more likely to have missed doses in the previous 3 days if they were taking ART medications three or more times per day or had to take one or more antiretrovirals on an empty stomach. A multivariate logistic regression model demonstrated that patients with less complex regimens (twice daily or less in frequency, no food-dosing restrictions) who correctly understood the dosing and food restrictions of their ART regimen were less likely to have skipped doses in the past three days (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.2-0.7) than those with more complex regimens. Younger age and higher CD4 count were also associated with a reduced likelihood of skipping doses. No association was found between adherence and race/ethnicity, current or past injection drug use, or education. CONCLUSIONS: Self-reported adherence is better among patients with less complex ART regimens. This is in part because patients' understanding of regimen dosing decreases as regimen complexity increases. Therefore, simplifying antiretroviral regimens may have an important role in improving patients' adherence.

HIV counseling and testing of pregnant women in sub-Saharan Africa: experiences from a study on prevention of mother-to-child HIV-1 transmission in Dar es Salaam, Tanzania.

Abstract: The aim of this study was to determine the acceptability of HIV counseling and testing and participation in a mother-to-child HIV-1 transmission intervention study using antiretroviral therapy in Dar es Salaam, Tanzania, one of the sites for the Joint United Nations Program on AIDS (UNAIDS) multicenter Petra trial. HIV testing was offered to all pregnant women who visited three prenatal clinics in Dar es Salaam before 34 weeks' gestation. Group or individual pretest counseling was performed by trained midwives. Laboratory diagnosis of HIV infection was based on two sequential anti-HIV enzyme-linked immunosorbent assays. Posttest counseling was given 2 weeks later to women who wished to know their HIV status. HIV testing was offered to a total of 10,010 pregnant women from June 1996 to May 1998, of whom 76.4% (7647 of 10,010) agreed to be tested. The prevalence of HIV-1 infection was 13.7% (1050 of 7647). Overall, 68.1% (5205 of 7647) returned for their results. Of the HIV-1-seropositive respondents, 27.4% (288 of 1050) agreed to participate in the Petra trial after fulfilling the eligibility criteria. Only 16.7% (48 of 288) of the enrolled women disclosed their positive HIV serostatus to their sexual partners. The main reasons for not disclosing the HIV serostatus were fear of stigma and divorce. Sixty percent (29 of 48) of the informed sex partners agreed to be tested for HIV and 69% (20 of 29) tested HIV seropositive. Pregnancy recurrence rate was 4.4 per 100 women years (18 pregnancies during 408 women years of follow-up) with 10 of 18 (55.6%) women not wanting to carry the pregnancy to term. In conclusion, this information is useful in planning intervention programs for prevention of mother-to-child HIV-1 transmission and it shows that improvements are required in counseling.

The dynamic of adherence to highly active antiretroviral therapy: results from the French National APROCO cohort.

Abstract: Objectives Our objective was to describe the evolution of adherence to highly active antiretroviral therapy (HAART) over a 20-month period and its relationship with virologic success. Methods Self-reported adherence, clinical, and virologic data were collected 4 (M4), 12 (M12), and 20 (M20) months after initiation of a protease inhibitor-containing regimen in the French APROCO cohort. At each visit, patients were classified as nonadherent, moderately, or highly adherent, and HIV plasma RNA was determined. Results Among the 762 patients who were regularly followed until M20, the 436 patients who answered to all questionnaires, including adherence measurement, were selected for the analysis. The proportion of highly adherent patients was 55.7%, 62.2%, and 60.3% at M4, M12, and M20, respectively. A total of 137 patients (31.4%) was "always," 225 (51.6%) "sometimes," and 74 (17.0%) "never" "highly adherent" during follow-up. After multiple adjustment for known baseline predictors, virologic success after 20 months of HAART was more likely achieved in patients who were always (odds ratio [OR] 95% confidence interval [CI], 3.02 [1.64-5.58]) or sometimes (OR [95% CI], 2.15 [1.24-3.74]) "highly adherent." Conclusion Adherence behavior is a dynamic process. Continued adherence was associated with better response to therapy and should be encouraged to reduce the risk of virologic failure.

Provider assessment of adherence to HIV antiretroviral therapy.

Abstract: Background: Adherence assessment is an essential component of monitoring HIV antiretroviral therapy. Prior studies suggest that medical providers frequently estimate individual patient adherence inaccurately. Objective: We compared provider estimates of nonadherence to antiretroviral therapy with unannounced pill counts and structured patient interviews to determine the accuracy of adherence information obtained by providers and patients. Design, setting, and participants: Comparison of three adherence measures in homeless or marginally housed persons receiving HIV antiretroviral therapy (n = 45) and their providers (n = 35). Measurements: Provider estimate of percentage of pills taken; three successive patient structured reports of number of doses missed in the last 3 days; and three successive unannounced pill counts. Results: 13% (95% confidence interval [CI], 4%-22%) of patients were not following their regimen as directed. Provider-adherence estimate explained only 26% (95% CI, 6%-47%) of the variation in pill count adherence, whereas patient report explained 72% (95% CI, 52%-96%). The sensitivity and specificity of provider estimates of nonadherence, defined as <80% of pills taken by pill count, were 40% and 85%, respectively. The sensitivity and specificity of patient interview were 72% and 95%, respectively. Conclusions: Provider estimate of adherence was inaccurate whereas structured patient report was more closely related to pill count. Structured assessment over several short intervals may improve accuracy of adherence assessment in clinical practice.

Antiretroviral treatment simplification with nevirapine in protease inhibitor-experienced patients with hiv-associated lipodystrophy: 1-year prospective follow-up of a multicenter, randomized, controlled study.

Abstract: BACKGROUND Simpler and less toxic antiretroviral strategies are needed to maximize treatment compliance without sacrificing potency, at least for drug-experienced HIV-infected patients currently on regimens containing protease inhibitors (PIs). Small nonrandomized studies have suggested a beneficial role of PI-sparing regimens on lipodystrophy. OBJECTIVES To assess the virologic, immunologic, and clinical benefit of switching the PI to nevirapine in patients with HIV-associated lipodystrophy and sustained viral suppression before entry in the study. DESIGN Open-labeled, prospective, randomized, multicenter study. SETTING Seven reference inpatient centers for HIV/AIDS in Spain. PATIENTS One hundred six HIV-infected adults with clinically evident lipodystrophy who sustained HIV-RNA suppression for at least 6 months with PI-containing antiretroviral combinations. INTERVENTION Replacement of the PI with nevirapine during 48 weeks (Group A) versus continuing the prior PI (Group B). MEASUREMENTS Several virologic and immunologic analyses, standard and specific biochemical tests, and anthropometric and dual X-ray absorptiometry measurements. RESULTS At week 48, an HIV-1 RNA level <400 copies/ml was maintained in 79% and 77% of patients in Groups A and B, respectively, whereas 74% and 72% of patients had viral load levels <50 copies/ml. Absolute CD4+ counts significantly increased in both groups compared with baseline values, and a significant decrease in CD38+CD8+ cells was observed in Group A (p <.01) but not in group B. Overall, no significant changes in anthropometric or body shape measurements were found after 48 weeks. Fasting total cholesterol and triglyceride levels decreased in Group A (but not in Group B) compared with baseline values (p <.05), although no significant differences were seen between groups at the end of the study. Subjects in Group A reported a better quality of life (QOL) index than controls (p <.001), with the main reason reported being the greater simplicity of the new drug regimen. CONCLUSIONS Protease inhibitor-sparing regimens, including nevirapine, seem to be an effective alternative for PI-experienced patients. Nevirapine-based triple therapies allow maintained control of HIV-1 RNA levels and improve the immunologic response at 48 weeks of follow-up in patients with prior sustained virologic suppression. The switch to nevirapine significantly improved the lipidic profile in Group A, although there were no differences between groups at the end of the study. Additionally, no significant changes were seen in terms of lipodystrophy-related body shape changes 1 year after the PI substitution. Finally, nevirapine-containing regimens have a simpler dosing schedule, and this facilitates high adherence and improves QOL.

Cruising on the Internet highway.

Abstract: This study evaluated differences in sexual behavior and risk for sexually transmitted diseases (STDs) among men who have sex with men (MSM) who met their partners on-line and those who did not A self-administered questionnaire on sexual behavior was offered to a convenience sample of patients seeking public STD services Thirty-two percent of MSM patients reported meeting a sexual partner over the Internet in the past year MSM with on-line partners were younger, more likely to report sex with an HIV-positive person in the last year, and more likely to report casual partners in the last year compared with MSM with only off-line partners HIV-negative MSM with on-line partners were more likely than HIV-negative MSM with only off-line partners to have received money or drugs for sex in the past year and to report sex with an HIV-positive partner in the past year Although meeting partners on the Internet was common and associated with increased risk for STDs in MSM, it also presents new untapped opportunities for on-line health promotion and disease prevention

Effect of highly active antiretroviral therapy on the natural history of anal squamous intraepithelial lesions and anal human papillomavirus infection.

Abstract: The effect of highly active antiretroviral therapy (HAART) on the natural history of anal squamous intraepithelial lesions (ASIL)-the likely anal cancer precursor-and anal human papillomavirus (HPV) infection is unknown. ASIL severity and level of anal HPV DNA were evaluated among HIV-positive men who have sex with men (MSM) for at least 6 months before initiation of HAART. The results were compared with those from a 6-month period after initiation of HAART. Anal swabs for cytology and HPV studies were obtained, followed by high-resolution anoscopy and biopsy. Among men whose most severe pre-HAART diagnosis was atypical squamous cells of undetermined significance or low-grade ASIL, 18% (confidence interval [CI], 6-31%, 7 of 38) progressed and 21% (CI, 8-34%, 8 of 38) regressed 6 months after starting HAART. Seventeen percent (CI, 0-38%, 2 of 12) of study subjects who began with a normal diagnosis developed ASIL. Only 4% (CI, 0-10%, 1 of 28) of study subjects with high-grade ASIL regressed to normal. There was no reduction in the proportion of study subjects who tested positive for HPV DNA or HPV DNA levels after HAART initiation. The ASIL and HPV data were similar to those of the pre-HAART comparison period. These results indicate that HAART has little effect on either ASIL or HPV in the first 6 months after HAART initiation.

HIV-positive men's sexual practices in the context of self-disclosure of HIV status.

Abstract: Objective To examine whether disclosure of HIV-positive status to sex partners at risk for HIV infection is associated with safer sex practices and to examine the prevalence and correlates of specific disclosure/sexual behavior patterns. Methods Cross-sectional assessment of 206 HIV-positive men (41% homosexual, 35% bisexual, 24% heterosexual) sampled randomly at an outpatient HIV clinic in Los Angeles, who reported that their most recent sex partner was HIV-negative or of unknown serostatus. Unsafe sex was defined as unprotected anal or vaginal intercourse with that partner. Results Twenty-five percent of the men engaged in unsafe sex, and 48% of the total sample withheld disclosure from the partner. The prevalence of safer sex was not significantly higher among disclosers than among nondisclosers (unadjusted odds ratio = 1.29; 95% confidence interval: 0.69-2.45), and disclosure was not significantly associated with safer sex in any of 25 demographic or partner subgroups examined in the study. In the full sample, 40% of the men disclosed and engaged in safer sex (informed protection), 35% withheld disclosure and engaged in safer sex (uninformed protection), 12% informed their partner and engaged in unsafe sexual behavior (informed exposure), and 13% withheld disclosure and engaged in unsafe sex (uninformed exposure). Risky behavior patterns were associated with using alcohol/drugs before sex, having an HIV-unknown partner, being less emotionally involved with one's partner, and testing seropositive in the previous 3 years. Conclusions Interventions for seropositive men that focus primarily on increasing disclosure of serostatus to sex partners may not reduce the prevalence of unsafe sex. Interventions are needed to address the social and psychologic processes that give rise to risky behavior patterns in HIV-infected men. Improved substance abuse counseling also may be needed.

Pharmacokinetic interaction between nevirapine and rifampicin in HIV-infected patients with tuberculosis.

Abstract: To determine whether rifampicin reduces serum concentrations of nevirapine and whether nevirapine modifies serum concentrations of rifampicin, levels of these agents were determined at steady state by high-performance liquid chromatography in 10 HIV-infected patients with tuberculosis. The median area under the curve (AUC) 0-12h of nevirapine before and after rifampicin was 56.2 and 32.8 microg/ml per hour, respectively ( p =.04). This represents a 31% reduction in serum nevirapine concentrations. The C(max) decreased from 5.6 to 4.5 microg/ml ( p =.04), which represented a 36% reduction. A 21% decrease in the C(min) was not statistically significant. Exposure to rifampicin did not significantly differ between those patients who were receiving and were not receiving nevirapine. However, our study shows that rifampicin reduces serum exposure to nevirapine. The clinical implications for this reduction remain to be established. Given that the lowest trough serum concentration of nevirapine exceeded by more than 40 times the protein binding adjusted median infective dose (IC(50)) of wild-type HIV in all patients, we suggest that there is no need to increase nevirapine dosage when it is given with rifampicin.

Nonnucleoside reverse transcriptase inhibitor resistance

Abstract: Although understanding of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance is less clearly established than that of other classes of antiretroviral drugs, certain facts have been established. The treatment-associated genetic mutation profiles of the available NNRTIs have been mapped, and resistance has been found to develop rapidly after initiation of NNRTI therapy. Despite the chemical diversity of the NNRTIs, cross-resistance among agents of this class is nearly universal. Although the viral replicative capacity ("fitness") of NNRTI-induced viral variants has not been extensively studied, available data suggest that NNRTI-selected mutations confer little damage to viral fitness, and thus a single point mutation produces a strain that is both resistant and fit. Furthermore, with continued therapy, viral evolution persists, creating species with greater numbers of mutations and higher level phenotypic resistance. Taken together, these facts suggest that continued use of NNRTIs after emergence of resistance will produce variants of complex mutational patterns that limit future treatment options, and, therefore, strong consideration should be given to discontinuing NNRTIs after virologic failure is confirmed. This article describes the scientific literature establishing the efficacy and limitations of NNRTI therapy and attempts to define a role for this class of drug in the long-term treatment of HIV-1 disease.

Sexual and reproductive life of women informed of their HIV seropositivity: a prospective cohort study in Burkina Faso.

Abstract: Background: In the context of the DITRAME-ANRS 049 research program that evaluated interventions aimed at reducing mother-to-child transmission of HIV (MTCT) in Bobo-Dioulasso (Burkina Faso), Voluntary HIV counseling and testing (VCT) services were established for pregnant women. HIV-infected women were advised to disclose their HIV serostatus to their male partners who were also offered VCT, to use condoms to reduce sexual transmission, and to choose an effective contraception method to avoid unwanted pregnancies. This study aimed at assessing how HIV test results were shared with male sexual partners, the level of use of modern contraceptive methods, and the pregnancy incidence among these women informed of the risks surrounding sexual and reproductive health during HIV infection. Methods: From 1995 to 1999, a quarterly prospective follow-up of a cohort of HIV-positive women. Results: Overall, 306 HIV-positive women were monitored over an average period of 13.5 months following childbirth, accounting for a total of 389 person-years. The mean age at enrollment in the cohort was 25.1 (standard deviation, 5.2 years). In all, 18% of women informed their partners, 8% used condoms at each instance of sexual intercourse to avoid HIV transmission, and 39% started using hormonal contraception. A total of 48 pregnancies occurred after HIV infection was diagnosed, an incidence of 12.3 pregnancies per 100 person-years. Pregnancy incidence was 4 per 100 personyears in the first year of monitoring and this rose significantly to 18 per 100 person-years in the third year. The only predictor of the occurrence of a pregnancy after HIV diagnosis was the poor outcome of the previous pregnancy (stillbirth, infant death). Severe immunodeficiency and change in marital status were the only factors that prevented the occurrence of a pregnancy after HIV diagnosis. Conclusion: Our study shows a poor rate of HIV test sharing and a poor use of contraceptive methods despite regular advice and counseling. Pregnancy incidence remained comparable with the pregnancy rate in the general population. To improve this situation, approaches for involving husbands or partners in VCT and prevention of MTCT interventions should be developed, evaluated, and implemented.

Evolution of cervical abnormalities among women with HIV-1: evidence from surveillance cytology in the women's interagency HIV study.

Abstract: Objective: To determine incidence, progression, and regression rates for abnormal cervical cytology and their correlates among women with HIV. Methods: In a multicenter prospective cohort study conducted October 1, 1994, through September 30, 1999 at university, public, and private medical centers and clinics, 1639 HIV-seropositive and 452 seronegative women were evaluated every 6 months for up to 5 years using history, cervical cytology, T-cell subsets, and quantitative plasma HIV RNA. Human papillomavirus (HPV) typing at baseline was determined by polymerase chain reaction. Cytology was read using the Bethesda system, with any smear showing at least atypia considered abnormal. Poisson regression identified factors associated with incident cytologic abnormalities whereas logistic regression identified those associated with progression and regression after an abnormality. Results: At least one abnormal smear was found during all of follow-up among 73.0% of HIV-seropositive patients and 42.3% of seronegatives (p 200/mm 3 and HIV RNA levels <4000/ml of similar HPV status. Conclusions: Although HIV infected women were at high risk for abnormal cytology, high-grade changes were uncommon. HIV status, HPV detection, CD4 lymphocyte count, and HIV RNA level predicted the incidence of cervical cytologic abnormalities. Progression was significantly increased only among the most immuno-suppressed women, while regression was significantly reduced in all HIV seropositive women except those with the best controlled HIV disease.

Impact of HIV infection on mortality in a cohort of injection drug users.

Abstract: The prevalence of HIV has been rising among injection drug users (IDUs) and AIDS is now an important cause of death among that population. We tracked mortality and recorded detailed causes of death in the Vancouver Injection Drug Users Study (VIDUS). This is an open cohort of over 1,400 active IDUs that began in May 1996. At enrollment and at semiannual follow-up visits, a trained interviewer administers a detailed semistructured questionnaire. Mortality was recorded during follow-up and detailed causes of death were collected from coroner's reports, hospital records, and the provincial (British Columbia) registry. Causes of death were obtained on 125 participants. Overall, the leading cause of death was overdose accounting for 25% of deaths among HIV-positive participants and 42% among HIV-negative participants. Of the 65 deaths among HIV-positive individuals, 22 (34%) were HIV related. Mortality was associated with older age (adjusted hazards ratio [AHR], 1.03 per year), HIV positivity (AHR, 2.67), injection cocaine use (AHR, 2.23) and methadone treatment (AHR, 0.47). The high rate of HIV in this population has added significantly to the burden of illness and death in this marginalized population.

Prevalence and correlates of anemia in a large cohort of HIV-infected women: Women's Interagency HIV Study.

Abstract: Anemia is a common manifestation of HIV infection, occurring in approximately 30% of patients with asymptomatic infection and in as many as 75% to 80% of those with AIDS. Anemia has been associated with decreased quality of life and decreased survival. We performed a cross-sectional study nested within a multicenter prospective cohort study to describe the prevalence of anemia in 2056 HIV-infected and 569 HIV-negative women as well as to define the demographic, clinical, immunologic, and virologic correlates of anemia among HIV-infected women. A total of 37% of HIV-positive women and 17% of HIV-negative women had hemoglobin levels < 12 g/dl (p < .001). Factors associated with anemia in HIV-positive and HIV-negative women included mean corpuscular volume (MCV) < 80 fl (p < .001) and black race (p < .001). Among HIV-infected women, multivariate logistic analyses revealed that African American race (p < .0001), MCV < 80 fl (p < .0001), CD4 count < 200 per microliter (p <.0001), higher HIV RNA in plasma (p = .02), current use of ZDV (p = .01), and history of clinical AIDS (p = .004) were all independent predictors of anemia. These data indicate that worsening parameters of HIV disease are associated with anemia among HIV-infected women. Black women and women with low MCV values are at increased risk for anemia independent of HIV status.

Interleukin-7 receptor expression on CD8(+) T cells is reduced in HIV infection and partially restored with effective antiretroviral therapy.

Abstract: Interleukin (IL)-7 enhances CD8 T-cell proliferation and cytolytic activity. The expression of its receptor, CD127 (IL-7R alpha), may therefore be important in the immunopathogenesis of HIV disease. CD127 expression on CD8(+) T cells from HIV seronegative controls, untreated HIV-seropositive patients, and HIV-positive patients receiving antiretroviral therapy with sustained viral suppression was analyzed by flow cytometry in a cross-sectional study. Among healthy controls, 65% of CD8 cells expressed CD127 ( n = 7). This dropped to 21.6% among untreated HIV-positive patients ( n = 16), and approached normal levels (47.7%) in HIV-positive individuals on effective therapy ( n = 20). The same pattern was observed for naive (CD45RA(+) ) and memory (CD45RO(+) ) CD8(+) T cells but changes were more extreme within the memory cell population. Duration of viral suppression was the only parameter evaluated that correlated with extent of CD127 expression in treated patients. Impairment of CTL activity in HIV disease may be caused, in part, by downregulation of IL-7 receptor expression. Improved immune function with effective antiretroviral therapy is associated with recovery of this molecule. The correlation between virologic suppression and apparent CD127 recovery suggests that essential cytokine signaling pathways may be restored with sustained inhibition of viral replication.

Frequency of genotypic and phenotypic drug-resistant HIV-1 among therapy-naive patients of the German Seroconverter Study.

Abstract: Genotypic and phenotypic resistance of viral reverse transcriptase (RT) and protease (PR) was determined for 64 therapy-naive, HIV-1-infected seroconverters of the German Seroconverter Study coordinated by the Robert Koch-Institut, Berlin. The date of seroconversion of patients and the laboratory, clinical, and therapeutic follow-up data were documented. Samples were collected between 1996 and 1999. Phenotypic resistant HIV-1 were found in 8 (13%) seroconverters; in most cases resistance was weak and mainly directed against RT inhibitors (4 nucleoside reverse transcriptase inhibitors [NRTIs], 2 nonnucleoside reverse transcriptase inhibitors [NNRTIs], 1 combination NRTI/NNRTI). Only one infection with a weak PR inhibitor resistance was identified. Transmission of multidrug-resistant HIV-1 has not yet been observed. Frequently at least one or more amino acid mutations associated with antiretroviral drug resistance were detected by genotypic analysis. The mean number of resistance-associated mutations in the RT of the transmitted virus has increased significantly since 1996. Studies have shown the improved benefit of initial antiretroviral therapy if based on genotypic resistance data. In view of the considerably high level of transmission of resistant HIV-1 in Germany, which is also seen in other studies in Europe and the United States, we suggest determining the genotypic resistance pattern before starting therapy of newly HIV-1-infected patients.

Influence of a partner's HIV serostatus, use of highly active antiretroviral therapy, and viral load on perceptions of sexual risk behavior in a community sample of men who have sex with men.

Abstract: Objective: To assess the perceptions of gay and bisexual men concerning the risk of HIV transmission through various sexual practices with a new sex partner depending on that partner's disclosed HIV status, antiretroviral treatment status, and viral load. Methods: Study participants read four different scenarios describing sexual situations with a new partner and rated each scenario for risk of HIV transmission. HIV status and antiretroviral treatment status disclosed by the new sex partner were varied across four scenarios: unknown HIV status; HIV-negative; HIV-positive and not taking highly active antiretroviral therapy (HAART); and HIV-positive and taking HAART with an undetectable viral load. Results: Study participants were 472 men attending a gay pride festival who reported that they were HIV-negative. Eighty-nine percent of the men were white, and the mean age of the study participants was 35.8 years. Of the four scenarios, sex with an HIV-positive partner not taking HAART was rated as posing the greatest risk. Sex with an HIV-positive partner taking HAART who had an undetectable viral load was not consistently viewed as riskier than sex with an HIV-negative partner or a man with an unknown HIV status. Conclusions: The current study provides preliminary evidence for the effect of disclosure of HIV serostatus, use of HAART, and the presence of an undetectable viral load on the perceptions of sexual risk for HIV-negative men. The findings suggest that some gay and bisexual men judge risk based on the perceived HIV status of their sex partners and not on the general assumption that all sex partners entail equal risk, as many prevention campaigns have emphasized.

Association between insulin resistance and hepatitis C virus chronic infection in HIV-hepatitis C virus-coinfected patients undergoing antiretroviral therapy.

Abstract: Insulin resistance (IR) in the context of highly active antiretroviral therapy (HAART) is becoming more common in HIV-infected patients. Patients with chronic hepatitis C virus (HCV) infection have an increased risk of IR and type 2 diabetes mellitus. A cross-sectional study was performed to investigate whether chronic HCV infection constitutes a risk factor for IR in HIV-HCV-coinfected patients undergoing HAART. Inclusion criteria were positive HCV viremia and a sustained increase of alanine aminotransferase of at least twice the normal value. A total of 29 HIV-HCV patients, 76 HIV patients, and 121 HCV controls were tested for IR and body mass index (BMI). IR was measured using the homeostasis model assessment. In HIV-HCV and HIV patients, fat redistribution and lipid profile were assessed. There was no significant difference in age, CD4 cell count, HIV viral load, or duration of HAART between the HIV-HCV and HIV groups. HIV-HCV patients and HCV controls had a significant increase in IR when compared with HIV patients (0.25 +/- 0.28 and 0.21 +/- 0.34 versus 0.04 +/- 0.37; p =.01 and p =.003, respectively). Lipoatrophy was observed more frequently in HIV-HCV patients in comparison with HIV patients (41% versus 14%; p =.003). In HIV-HCV patients, total cholesterol and triglyceride levels were significantly lower than in HIV patients. In multivariate analysis, IR, BMI, triglyceride levels, and peripheral fat wasting were the independent variables associated with HCV infection. Our findings suggest that chronic HCV infection is a significant factor associated with the development of metabolic abnormalities and with modifications in body composition in HIV patients receiving antiretroviral treatment.

Homozygous and heterozygous CCR5-Delta32 genotypes are associated with resistance to HIV infection.

Abstract: Objective To investigate evidence for resistance to HIV-1 infection associated with the heterozygous genotype CCR5-+/Delta32 and with the homozygous genotype CCR5-Delta32/Delta32, which results in a nonfunctional CCR5 receptor. Design Cohort study of initially HIV-seronegative high-risk individuals from eight different cities. Enrollment data were analyzed to investigate the association of demographic factors and risk behaviors with CCR5 genotypes on the assumption that increased genotype prevalence among persons with histories of longer or more intensive exposure to HIV would indicate HIV resistance associated with that genotype. Longitudinal data were analyzed to investigate the association of HIV seroincidence with CCR5 genotypes. The cohort of 2996 individuals included 1892 men who have sex with men (MSM), 474 male injection drug users (IDUs), 347 women at heterosexual risk, and 283 female IDUs. Measurements CCR5 genotype, HIV serostatus, demographic factors, and risk behaviors during the 6 months before enrollment, followed by measurement of HIV seroincidence during the subsequent 18 months (for men) and 24 months (for women). Results Forty (1.3%) subjects were homozygous CCR5-Delta32/Delta32 and 387 (12.9%) were heterozygous CCR5-+/Delta32. All but 1 CCR5-Delta32/Delta32 individuals and 51 CCR5-+/Delta32 individuals were Caucasian. Among 1531 Caucasian MSM, CCR5-+/Delta32 individuals were present more frequently (22.3%) among those reporting unprotected receptive anal intercourse than among those not reporting this risk (15.9%) (p =.002), suggesting a selective advantage of the heterozygous genotype. CCR5-+/Delta32 individuals also had a significantly reduced relative risk of HIV seroconversion adjusted for unprotected receptive anal intercourse compared with CCR5-/+ individuals (relative risk = 0.30, 95% confidence interval [CI]: 0.08-0.97). CCR5-Delta32/Delta32 prevalence among Caucasian MSM was significantly associated with age among subjects recruited from high HIV seroprevalence cities (New York City and San Francisco) (odds ratio [OR] for each decade increase in age = 2.57, CI: 1.56-4.21) but not among those recruited from lower HIV prevalence sites (Boston, Chicago, Philadelphia, Seattle, and Providence/Pawtucket, Rhode Island) (OR = 1.20, CI: 0.75-1.89). Conclusions Cross-sectional and longitudinal analyses indicated that among high-risk HIV seronegative MSM, CCR5-+/Delta32 and CCR5-Delta32/Delta32 are associated with protection against HIV infection. These findings imply that strategies aimed at reducing susceptibility to HIV infection by blocking CCR5 receptor sites need not seek blockage of all receptor sites to achieve an imperfect but substantial degree of protection.

Cytokine Profile and Immunomodulation in Asymptomatic Human T-Lymphotropic Virus Type 1-Infected Blood Donors

Abstract: The modulation of the immune response has been used as therapy for clinical disorders associated with human T-lymphotropic virus type 1 (HTLV-1) infection. In this study, the cytokine profile was evaluated in 26 asymptomatic HTLV-1 blood donors. Additionally, both the cell responsible for producing interferon-gamma (IFN-gamma) and the role of exogenous interleukin (IL)-10 in downregulating IFN-gamma production were studied. Cytokine levels were determined in supernatants of unstimulated lymphocyte cultures by enzyme-linked immunosorbent assay. The levels of IFN-gamma, tumor necrosis factor-alpha, IL-5, and IL-10 were higher in supernatants of the lymphocyte cultures taken from HTLV-1-infected donors than in those taken from healthy subjects. Although depletion of CD8+ T cells and natural killer cells did not affect IFN-gamma production, depletion of CD4+ T cells significantly decreased IFN-gamma production. Furthermore, at a concentration of 2 ng/ml, IL-10 had only a minimum effect on IFN-gamma production, although at high concentrations (100 ng/ml), IL-10 decreased IFN-gamma production by 50% in HTLV-1-infected individuals. These data indicate that both T helper 1 and T helper 2 cytokines are elevated in HTLV-1 infection and that IL-10 in high concentrations modulates IFN-gamma production in these patients.

Willingness to volunteer in future preventive HIV vaccine trials: issues and perspectives from three U.S. communities.

Abstract: UNLABELLED This study examined perceived risks, benefits, and desired information related to willingness to volunteer in preventive HIV vaccine trials. SAMPLE Purposive sampling was used to select 90 participants among injecting drug users (Philadelphia, PA, U.S.A.); gay men (San Francisco, CA, U.S.A.); and black Americans (Durham, NC, U.S.A.). METHODS A qualitative interview guide elicited perceived benefits, risks, and desired information relating to trial participation. Themes were developed from the transcribed texts and from freelists. RESULTS Stated willingness to volunteer in a preventive HIV vaccine trial was similar across the three communities. Eight perceived benefits were reported, including self-benefits, altruism, and stopping the spread of AIDS. Seven perceived risks were reported, including negative side effects and vaccine safety issues, contracting HIV from the vaccine, and social stigmatization. Participants voiced the desire for eight types of information about issues relating to trust and confidentiality in the research process, health complications and later assistance, and vaccine trial methodology. CONCLUSIONS In this study, many benefits as well as risks of preventive HIV vaccine trial participation were cited. Scientists conducting preventive HIV vaccine trials need to address community perceptions of risks and provide information about the research if trial enrollment is to be diverse and successful.

Immune activation correlates better than HIV plasma viral load with CD4 T-cell decline during HIV infection.

Abstract: This study addressed the role of T-cell immune activation in determining HIV-1 plasma viral load and CD4+ T-cell blood levels during HIV-1 infection. A decrease of blood CD4 levels and CD4/CD8 ratios and an increase of CD8 levels in both treated (n = 35) and untreated (n = 19) HIV-positive individuals were more strongly correlated to immune activation (log percentage of HLA-DR+CD3+ cells; R = -0.78, R = -0.77, and R = 0.58, respectively; p <.0001) than to CD4 T-cell proliferation (log percentage of Ki-67+CD4+ cells; R = -0.57 [p <.0001], R = -0.48 [p <.001], and R = 0.37 [p <.01], respectively) or to viral load (R = -0.36 [p <.01], R = -0.23 [p =.09], R = 0.13 [p =.35], respectively). Because almost half of the Ki-67+CD4+ cells were also positive for CTLA-4 (a marker for activated nonproliferating cells), the correlation of CD4 levels to Ki-67 expression is only partially related to cell proliferation and more likely represents mainly immune activation of the cells without proliferation. Taken together, these results suggest that immune activation is the major determinant of CD4 decline and should therefore be considered central for the monitoring of HIV infection and its outcome after antiviral treatment.

Lipodystrophy in HIV-infected children is associated with high viral load and low CD4+ -lymphocyte count and CD4+ -lymphocyte percentage at baseline and use of protease inhibitors and stavudine.

Abstract: Alterations in regional fat, often associated with abnormalities in lipid and insulin metabolism, have been reported in HIV-infected adults. To determine whether similar abnormalities occur in children with HIV, patterns of change in regional body fat distribution were determined by dual energy x-ray absorptiometry in 28 prepubertal HIV-infected children. Eight (29%) children experienced lipodystrophy (LD), defined as extremity lipoatrophy together with trunk fat accumulation. Despite a mean body weight increase of 2.9 +/- 2.4 kg, children with LD experienced a mean loss of total fat in contrast to children without LD who increased total fat (-0.151 +/- 0.324 versus 0.981 +/- 1.041 kg; p <.01). Children with LD had significantly higher levels of HIV RNA and lower CD4 count and percentage at baseline. LD was associated with use of protease inhibitors or stavudine, (odds ratio [OR], 7.0, 95% confidence interval [CI], 1.1-45.2, p =.04; OR, 9.0, 95% CI, 1.4-59.8, p =.03, respectively). This observational study suggests that during a time in childhood when accumulation of extremity and trunk fat is expected, some HIV-infected children experience changes in fat distribution that are similar to HIV-associated LD reported in adults. Studies to determine whether HIV-infected children with changes in regional fat also experience increases in "atherogenic" lipids and insulin resistance as described in adults with HIV-associated LD are warranted.