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In this issue, Bernard and colleagues describe the relationship between the level of indinavir in hair, virologic response, and the occurrence of resistant HIV mutations. Their article provides evi...

Background The optimal virologic and immunologic stage at which to initiate antiretroviral therapy in individuals infected with human immunodeficiency virus type 1 (HIV-1) is undefined. Methods Among 1054 HIV-1–infected women in a prospective cohort study, we determined the time from initiation of highly active antiretroviral treatment (HAART) to acquired immunodeficiency syndrome (AIDS) and death. Results Median follow-up was 3.4 years. Of 553 women without AIDS at HAART initiation, 62 (11%) developed AIDS. Compared with women with CD4 + cell counts greater than 350/µL at HAART initiation, women with cell counts of 200 to 350/µL and less than 200/µL had relative hazards (RHs) for progression to AIDS of 0.93 (95% confidence interval [CI], 0.46-1.86) and 2.48 (95% CI, 1.39-4.42), respectively. Compared with those with HIV-1 RNA values less than 5000 copies/mL, women with 5000 to 50 000 copies/mL and greater than 50 000 copies/mL had RHs of 1.39 (95% CI, 0.74-2.64) and 2.09 (95% CI, 1.09-3.99), respectively. Among women with AIDS at HAART initiation (n = 501), RHs of death were 1.97 (95% CI, 0.84-4.66) and 3.35 (95% CI, 1.59-7.08) with CD4 + cell counts of 200 to 350/µL and less than 200/µL, respectively, relative to those with greater than 350/µL, and 1.90 (95% CI, 0.84-4.30) and 3.70 (95% CI, 1.81-7.54) for those with HIV-1 RNA values of 5000 to 50 000 and greater than 50 000 copies/mL, respectively, relative to those with less than 5000 copies/mL. Conclusions Progression to AIDS and death was predicted by pre-HAART values of less than 200/µL for CD4 + cells and greater than 50 000 HIV-1 RNA copies/mL, indicating that deferral of HAART until the CD4 + cell count is between 350 and 200/µL is a valid strategy in the clinical management of HIV-1 infection.

OBJECTIVES To identify factors associated with the use of medical services, and to test a model of access to care, among HIV-infected women. METHODS A cross-sectional telephone survey was administered to 213 HIV-infected women. Outcomes were having a primary care provider, and use of primary care and emergency health services. Predictors included characteristics of the population-at-risk and of the health care system. RESULTS Ninety-three percent of respondents had a primary care provider. Linear regression found age >45 years (p = .002), perceiving greater barriers to getting to a clinic (p = .04) and greater benefits from medications (p = .03), lack of problems with appointment times (p = .02), having AIDS (p = .01), shorter appointment waiting times (p = .0003), and greater cost of travel to care (p = .001) were associated with a greater number of primary care visits. Thirty-seven percent missed at least 1 primary care appointment. In logistic regression, lack of insurance (odds ratio [OR] = 2.76), current injection drug use (OR = 2.89) and difficulty remembering appointments (OR = 2.36) were associated with having missed any appointments. CONCLUSIONS Characteristics of the population-at-risk and of the health care system both make important contributions to primary care service use.

The use of herbs has been advocated as an alternative treatment strategy for human immunodeficiency virus-related illness. To describe the use of medicinal herbs among acquired immunodeficiency syndrome clinic patients and to investigate possible toxic effects, we interviewed 114 randomly selected patients attending a university-based acquired immunodeficiency syndrome clinic and performed a structured review of the literature to identify potential adverse effects of herbal use. Twenty-five participants (22%) reported using one or more herbal products in the past 3 months. Of those taking herbs, six (24%) were unable to identify the herb that they had used. The mean number of herbal tablets taken was 4.5 tablets per day, and 12 patients (48%) reported taking herbs for longer than 90 days. The median cost to patients for their herbs was $18 per month. Of those taking herbs, five (20%) stated that their primary medical provider was unaware of their herb use, and four (16%) were involved in clinical drug trials while using herbs. Several patients reported taking herbs in doses at which potential adverse effects were identified in our literature review. These adverse effects include dermatitis, nausea, vomiting, diarrhea, thrombocytopenia, coagulopathies, altered mental status, hepatotoxicity, and electrolyte disturbances. Seven patients (28%) reported experiencing symptoms that could have been caused by one or more of the herbal products that they were taking. Physicians and clinical investigators need to inquire about patients' use of herbs. Patient care and clinical trials could be distorted because pharmacologic effects of herbs can resemble commonly occurring symptoms in human immunodeficiency virus disorders as well as side effects of prescribed or investigational medications. ( Arch Intern Med . 1991;151:2281-2288)

Ninety-seven male homosexuals with the acquired immunodeficiency syndrome or other group IV human immunodeficiency virus disease were studied for anal human papillomavirus infection and intra-anal cytological abnormalities. Human papillomavirus DNA was detected in 52 subjects (54%), and 38 subjects (39%) were found to have abnormal anal cytological findings; anal intraepithelial neoplasia was detected in 15 specimens (15%). Abnormalities on anal cytological smear were significantly associated with the presence of human papillomavirus DNA, with a risk ratio of 4.6. Infection with multiple human papillomavirus types was common (12%) and was associated with a risk ratio for cytological abnormalities of 39.0. Median T4 counts of subjects with abnormal cytological findings were significantly lower than those with normal findings. These studies indicate that immunosuppressed male homosexuals have a high prevalence of anal human papillomavirus infection and anal intraepithelial neoplasia, and this population may be at significant risk for the development of anal cancer. (JAMA. 1990;263:2911-2916)

Sublethal doses of γ radiation are known to inhibit total RNA synthesis in the ciliate protozoan Tetrahymena . To determine if the synthesis of a particular class of RNA is preferentially inhibited, pulse-labeled RNA was isolated from normal exponentially growing cells, irradiated cells, and cells in which total RNA synthesis had recovered to the pre-irradiation level. The RNAs were analyzed by SDS-polyacrylamide gel electrophoresis and oligo(dT)-cellulose column chromatography. Inhibition of RNA synthesis primarily involves ribosomal RNA. However, radiation does not cause a delay in the processing of precursor rRNA or a preferential loss of either of the mature rRNAs. Following irradiation, poly(A)-containing RNA [poly(A+)RNA] is synthesized at a rate up to three times greater than the control rate. The elevated poly(A+)RNA synthesis occurs during the period of depressed rRNA synthesis and even after rRNA synthesis has recovered to its pre-irradiation rate. While the sizes of the total cellular ribonucleoside triphosphate pools are depressed in the irradiated cells, these pools probably do not represent the actual compartments containing the precursors for RNA synthesis, and the observed changes cannot explain the modifications in macromolecular synthesis in irradiated Tetrahymena .

Among 115 heterosexual men who presented with genital ulcers to a sexually transmitted disease clinic in Nairobi, Kenya, the prevalence of serum antibody to HIV was 16.5%. A past history of genital ulcers was reported by 12 (63%) of 19 men with antibody to HIV versus 30 (31%) of 96 without antibody (P = 0.008). HIV infection was also positively associated with lack of circumcision, but was not associated with the etiology of the current genital ulcer. Logistic regression analysis (adjusted for age, number of recent sex partners, recent prostitute contact, circumcision, tribal ethnic identity, past history of urethritis, and current diagnoses) confirmed only the association between prior history of genital ulcer disease and HIV infection; (P = 0.04, odds ratio 2.35, 95% confidence limits, 1.01-5.47). The incidence of genital ulcers, particularly chancroid, is much higher in parts of Africa than in Europe or North America. This may contribute to the increased risk of heterosexual transmission of HIV in Africa. Aggressive control of chancroid and syphilis may offer one very feasible approach to reducing transmission of HIV in this region.

The development of AIDS interventions for adolescents is hindered by the lack of data on the conditions that influence high‐risk sexual behavior. We examined psychosocial correlates of condom use and multiple partner sex for a sample of sexually‐active heterosexual adolescent women. Respondents reported higher levels of vaginal intercourse than the “average” adolescent. A minority were engaging in anal intercourse. Condom use was associated with perceived enjoyment of condoms and communication skills. Number of sexual partners was associated with susceptibility beliefs, social norms, and sexual communication skills. The findings support the general observation that AIDS interventions with adolescents should build sexual communication skills, address motivational issues, and teach people how to enjoy safe‐sex activities.

Are persons with the human immunodeficiency syndrome (HIV) and acquired immune deficiency syndrome (AIDS) denied dental care? Past surveys found that dentists don’t want to treat these patients. Yet, the results discussed in this article of three studies—conducted in Los Angeles; San Francisco; Seattle; and Tacoma, Wash—assessing the experience of persons with AIDS or risk factors for the disease in seeking dental care found that denial of care is not as widespread as expected. Three studies were conducted to assess the experiences of persons with acquired immune deficiency syndrome (AIDS) or risk factors for the disease in seeking dental care in Los Angeles; San Francisco; Seattle; and Tacoma, WA. Given previous reports from surveys of dentists that they would be reluctant to provide care to people from these groups, widespread denial of care was expected. Our two surveys conducted in San Francisco, however, showed that only 1.3% and 10.8% had been denied care by a dentist. These data suggest that dentist reactions to people with AIDS are more favorable than has previously been suggested, although denial of care is still a problem to some extent.

Objectives. We assessed the association between initiation of highly active antiretroviral treatment (HAART) regimens and sexual risk behaviors among HIVinfected women. Methods. We analyzed data from 724 women who initiated HAART between January 1996 and January 2001 and who had pre-HAART viral loads at or above 400 copies per milliliter. Results. Sexually active women were less likely (odds ratio [OR] = 0.79) to report 2 or more partners during a 6-month period after HAART initiation than before HAART initiation. However, the risk for unprotected sex was higher after HAART initiation than before HAART initiation among all sexually active women (both those who reported 2 or more partners [OR = 1.84] and those who reported 1 partner [OR = 1.22]). Conclusions. Sexual risk behaviors are associated with receipt of therapy but not with therapeutic response, indicating a risk for transmission among female HAART recipients.

Objective: The purpose of this study was to describe the variability in highly active antiretroviral therapy (HAART) regimens over time, the extent to which individuals switch, and the characteristics of those who are switching. Methods: We evaluated data collected between 1994 and 2000 from 1056 HIV-positive women enrolled in the Women's Interagency HIV Study (WIHS) who reported initiating HAART. We described the variability and prevalence of changes in HAART regimens between semiannual visits, estimated time to switch using Kaplan-Meier methods, investigated factors associated with a first switch using Cox proportional hazards models, and compared disease markers among women switching or remaining on unchanged HAART regimens. Results: We demonstrated a 13-fold increase in the number of unique HAART regimens reported since mid-1996 and showed that the amount of time spent on the first, second, or third regimen is similar, with an 8-month median time to switching or discontinuing the initial HAART regimen. Women who switched had a lower mean CD4 cell count and were more likely to have HIV RNA levels greater than 400 copies/mL. Overall, the percentage of women switching decreased over the course of follow-up (to 37% in September 2000), although the percentage discontinuing therapy altogether increased 2-fold. Conclusion: Our findings on the relatively high rate of HAART switching emphasize the complexity of managing and evaluating these therapies.

Applicability of randomized controlled clinical trial (RCT) results to 'real world' situations is dependent on the comparability of trial participants to general patient populations. A full disclosure of criteria employed for trial enrollment is necessary for clinicians to assess generalizability. We sought to assess both the impact on generalizability and the disclosure rate of enrollment criteria for 32 major HIV RCTs in the AIDS Clinical Trial Group (ACTG) and Community Programs for Clinical Research on AIDS (CPCRA) trial networks.Eligibility criteria were compared in complete protocols to criteria listed in publications from these 32 NIH-funded HIV RCTs. We then applied these criteria to the Women's Interagency HIV Study (WIHS), the largest cohort study of HIV-infected women in the US.When applied to WIHS, eligibility criteria from protocols excluded 0-67.6% (median 42%) of WIHS participants (50.6% excluded from ACTG trials). Eligibility criteria in publications excluded 0-62% (median 19.6%) of WIHS (21.2% excluded from ACTG trials). The number of women in WIHS seemingly ineligible for trial participation per enrollment criteria listed in publications averaged only 60% of those actually excluded based on the protocols.We found that HIV RCT eligibility criteria excluded a large proportion of a representative cohort of HIV-infected women from trial participation. Furthermore, trial publications are not fully reflective of protocols in terms of disclosing eligibility criteria. Standardization and full disclosure of trial methodology will allow clinicians and researchers to more fully assess the generalizability of findings to their patient populations.

Methods Participants using either DMPA (n=15) or the LNG iUS (n=19) for at least 3 months and women using no hormonal contraceptives (n=24) were recruited. Endocervical curettage, endocervical cytobrush, and endometrial biopsy were obtained from all women. Expression of T cell activation markers, memory/effector differentiation markers and HIV co receptors were assessed by multiparameter flow cytometry. CD4+ and CD8+ T cells producing CD107a, IL-10, IL-2, IFNg, MIP1b and IL-17 were measured after stimulation with PMA/ionomycin or staphylococcal enterotoxin B (SEB).