Evaluating the association of single-nucleotide polymorphisms with tenofovir exposure in a diverse prospective cohort of women living with HIV.

Higher exposure to tenofovir (TFV) increases the risk for kidney function decline, but the impact of genetic factors on TFV exposure is largely unknown. We investigated whether single-nucleotide polymorphisms (SNPs, n=211) in 12 genes are potentially involved in TFV exposure. Participants (n=91) from the Women's Interagency HIV Study, underwent a 24 h intensive pharmacokinetic sampling of TFV after witnessed dose and TFV area under the time-concentration curves (AUCs) were calculated for each participant. SNPs were assayed using a combination of array genotyping and Sanger sequencing. Linear regression models were applied to logarithmically transformed AUC. Those SNPs that met an a priori threshold of P<0.001 were considered statistically associated with TFV AUC. ABCG2 SNP rs2231142 was associated with TFV AUC with rare allele carriers displaying 1.51-fold increase in TFV AUC (95% confidence interval: 1.26, 1.81; P=1.7 × 10-5). We present evidence of a moderately strong effect of the rs2231142 SNP in ABCG2 on a 24 h TFV AUC.

The cascade of care in the Eastern European country of Georgia.

OBJECTIVES: Individual and public health benefits of antiretroviral therapy (ART) rely on successful engagement of HIV-infected patients in care. We aimed to evaluate the HIV care continuum in the Eastern European country of Georgia. METHODS: The analysis included all adult (age ≥ 18 years) HIV-infected patients diagnosed in Georgia from January 1989 until June 2012. Data were extracted from the national HIV/AIDS database as of 1 October 2012. The following stages of the HIV care continuum were quantified: HIV infected, HIV diagnosed, linked to care, retained in care, eligible for ART and virologically suppressed. RESULTS: Of 3295 cumulative cases of adult HIV infection reported in Georgia, 2545 HIV-infected patients were known to be alive as of 1 October 2012, which is 52% of the estimated 4900 persons living with HIV in the country. Of the 2545 persons diagnosed with HIV infection, 2135 (84%) were linked to care and 1847 (73%) were retained in care. Of 1446 patients eligible for ART, 1273 (88%) were on treatment and 985 (77%) of them had a viral load <400 HIV-1 RNA copies/mL. Overall, 39% of those diagnosed and 20% of those infected had a suppressed viral load. CONCLUSIONS: The findings of our analysis demonstrate that the majority of patients diagnosed with HIV infection are retained in care. Loss of patients occurs at each step of the HIV care continuum, but the major gap is at the stage of HIV diagnosis. Reducing the number of persons living with undiagnosed HIV infection and simultaneously enhancing engagement in continuous care will be critical to achieve maximum individual and public health benefits of ART.

Racial differences in care among hospitalized patients with Pneumocystis carinii pneumonia in Chicago, New York, Los Angeles, Miami, and Raleigh-Durham.

BACKGROUND: While strategies for medical care for human immunodeficiency virus-related Pneumocystis carinii pneumonia (PCP) are well established, racial variations in care have not been evaluated. OBJECTIVE: To determine whether sociodemographic characteristics influence patterns of care and patient outcomes, by analyzing the use of diagnostic tests and anti-PCP medications and in-hospital mortality rates for persons who were hospitalized with human immunodeficiency virus-related PCP. METHODS: Retrospective chart review of a cohort of 627 Veterans Administration (VA) patients and 1547 non-VA patients with empirically treated or cytologically confirmed PCP who were hospitalized from 1987 to 1990. Outcomes included representative aspects of the process of care for PCP and short-term mortality rates. RESULTS: Among VA patients, black and Hispanic patients were not significantly different from white patients with regard to in-hospital mortality rates, use and timing of a bronchoscopy, or receipt of timely anti-PCP medications. Among non-VA patients, black and Hispanic patients were more likely to die in the hospital and less likely to undergo a diagnostic bronchoscopy in the first 2 days of hospitalization. These racial and ethnic group differences in the use of a bronchoscopy and in-hospital mortality among non-VA patients were almost fully accounted for by differences in health insurance status and hospital characteristics. CONCLUSIONS: Racial factors do not appear to be an important determinant of the intensity of diagnostic or therapeutic care among patients who are hospitalized with PCP. Variations in care are largely attributable to differences in health insurance and admitting hospital characteristics.

Medical care costs of intravenous drug users with AIDS in Brooklyn.

This article reports on a study of medical costs of intravenous drug users (IVDUs) with acquired immune deficiency syndrome (AIDS) in Brooklyn, NY, U.S.A. Sociodemographic and clinical data as well as information on medical resource use was gathered for 38 IVDUs with AIDS, all of whom belonged to minority racial/ethnic groups and were covered by Medicaid insurance. Data obtained through patient interviews and review of medical records indicated that the sample had mean annual medical charges of $33,002 per patient per year. Average inpatient charges were $24,171, with an average of 1.13 hospitalizations and 38.5 days of in-hospital care. Significantly more in-hospital care and higher inpatient charges on average were noted among patients who did not have a stable housing environment. Outpatient charges averaged $8,831, with 80% for pharmaceuticals. This estimate of medical charges and resource use, one of the first developed in a cohort of nonwhite individuals with i.v. drug use as a risk factor for human immunodeficiency virus infection, is about one third less than recent estimates reported from studies of cohorts of white homosexual men.

Delays in tuberculosis isolation and suspicion among persons hospitalized with HIV-related pneumonia.

BACKGROUND: Despite awareness of HIV-related tuberculosis (TB), nosocomial outbreaks of multidrug-resistant TB among HIV-infected individuals occur. OBJECTIVE: To investigate delays in TB isolation and suspicion among HIV-infected inpatients discharged with TB or Pneumocystis carinii pneumonia (PCP), common HIV-related pneumonias. DESIGN: Cohort study during 1995 to 1997. SETTING: For PCP, 1,227 persons who received care at 44 New York City, Chicago, and Los Angeles hospitals. For TB, 89 patients who received care at five Chicago hospitals. MEASUREMENTS: Two-day rates of TB isolation/suspicion. RESULTS: For HIV-related PCP, Los Angeles hospitals had the lowest 2-day rates of isolation/suspicion of TB (24.3%/26.6% vs 65.5%/66.4% for New York City and 62.8%/58.3% for Chicago, respectively; p < 0.001 for overall comparison by chi(2) test for each outcome measure). Within cities, hospital isolation/suspicion rates varied from < 35 to > 70% (p < 0.001 for interhospital comparisons in each city). The Chicago hospital with a nosocomial outbreak of multidrug-resistant TB from 1994 to 1995 isolated 60% of HIV-infected individuals who were discharged with a diagnosis of HIV-related TB and 52% discharged with HIV-related PCP, rates that were among the lowest of all Chicago hospitals in both data sets. CONCLUSION: Low 2-day rates of TB isolation/suspicion among HIV-related PCP patients were frequent. One Chicago hospital with low 2-day rates of TB isolation/suspicion among persons with HIV-related PCP also had low 2-day rates of isolation/suspicion among confirmed TB patients. That hospital experienced a nosocomial multidrug-resistant TB outbreak. Educational efforts on the benefits of early TB suspicion/isolation among HIV-infected pneumonia patients are needed.

Control of occupational hepatitis B among healthcare workers in the Czech Republic, 1982 to 1995.

Occupational hepatitis B remains a threat to healthcare workers (HCWs) worldwide, even with availability of an effective vaccine. Despite limited resources for public health, the Czech Republic instituted a mandatory vaccination program for HCWs in 1983. Annual incidence rates of acute hepatitis B were followed prospectively through 1995. Despite giving vaccine intradermally from 1983 to 1989 and intramuscularly as half dose from 1990 to 1995, rates of occupational hepatitis B decreased dramatically, from 177 cases per 100,000 workers in 1982 (before program initiated) to 17 cases per 100,000 in 1995. Among high-risk workers, the effect was even more dramatic (from 587 to 23 per 100,000). We conclude that strong public-health leadership led to control of occupational hepatitis B among HCWs in the Czech Republic, despite limited resources that precluded administering full-dose intramuscular vaccine for much of the program. Application of a similar program should be considered for other countries in regions that currently do not have a hepatitis B vaccination program.

Gender differences in early suspicion of tuberculosis in hospitalized, high-risk patients during 4 epidemic years, 1987 to 1990.

OBJECTIVES: To assess the degree to which, from 1987 to 1990, physicians suspected tuberculosis (TB) in the first 2 hospital days in human immunodeficiency virus (HIV)-infected patients with pulmonary disease. DESIGN: Retrospective cohort study. SETTING: 96 hospitals in five US cities. PATIENTS: 2,174 adult patients with acquired immunodeficiency syndrome discharged with a diagnosis of Pneumocystis carinii pneumonia from 1987 to 1990. The diagnosis generally was not known on admission. RESULTS: Physicians suspected TB in the first 2 hospital days in 66% of these patients in 1987, a rate that increased steadily to 74% in 1990. However, the extent to which physicians considered TB among female patients decreased from 76% to 71% over the 4 years. Controlling for confounding variables by multiple logistic regression, the odds that TB would be suspected early increased 1.8-fold among men (odds ratio [OR], 1.8; 95% confidence interval [CI95], 1.4-2.4), but not in women (OR, 0.6; CI95, 0.2-1.9). Among the five cities, the odds of early suspicion of TB increased most in New York City (OR, 3.9; CI95, 2.0-7.9). CONCLUSIONS: Physicians considered TB in a timely manner in an increasing majority of male, but not female, high-risk patients during the first years of TB resurgence in the United States. Physicians must be aware of the changing epidemiology of HIV and TB, as well as their practice patterns, to prevent nosocomial transmission of this disease.

The association of smoking and risk of condyloma acuminatum in women.

OBJECTIVE: To determine the relation between cigarette smoking and the incidence of genital warts in a cohort of human immunodeficiency virus (HIV)-infected women (without AIDS-defining conditions) (n = 148) and in HIV-negative women (n = 428). METHODS: Women were recruited between March 1990 and December 1993 from an urban, inner-city medical center and nearby community health centers. Woman initially free of genital warts (n = 576) were followed prospectively for up to 37 months, with an average of 14 months. RESULTS: The observed incidence of genital warts per 100 person-years was almost three times higher in smokers than in non-smokers, both in HIV-positive (13.3 versus 5.0, respectively) and HIV-negative women (1.5 versus 0.5, respectively). In a Poisson regression model adjusting for variables significantly related to genital warts, including sexual activity, current smokers were 5.2 times (95% confidence interval 1.02, 26.0) more likely to develop genital warts. The prevalence of human papillomavirus (HPV) by polymerase chain reaction at baseline examination and the incidence of other sexually transmitted diseases were similar is smokers and non-smokers. CONCLUSIONS: Our findings are compatible with the hypothesis that the rate of progression of symptomatic exophytic HPV disease is increased in smokers.

Pruritic skin lesions. A common initial presentation of acquired immunodeficiency syndrome.

During July 1983 to December 1984, we observed that 62 (46%) of 134 Haitian patients with acquired immunodeficiency syndrome had intensely pruritic eruptions for which neither specific causative nor categoric diagnoses could be established. These lesions were a presenting manifestation of acquired immunodeficiency syndrome in 79% of the patients and appeared a mean of 8 months before the diagnosis of either Kaposi's sarcoma or opportunistic infection. Lesions included erythematous round macules, papules, or nodules that first appeared on the extensor surface of the arms, but subsequently involved the legs, trunk, and face. Histologically, the lesions were characterized by varying degrees of mixed (predominantly eosinophilic) perivascular and perifollicular inflammatory cell infiltrates of the dermis. The lesions did not respond to any therapeutic regimens used and usually persisted throughout the acquired immunodeficiency syndrome illness. Demographic and laboratory data did not distinguish these patients from those without pruritic skin lesions.

Initial clinical assessment and management of HIV infection.

Management of HIV infection by the primary care physician can be easily integrated into the usual practice setting. The physician who understands the epidemiology of HIV disease, stays current with basic therapeutic concepts, and knows the patient and his or her living environment is in the best position to help the HIV-infected individual have a constructive and fulfilling life. When the primary care physician has a network of appropriate specialists for consultation and has appropriately integrated office and community-based nonmedical professionals into patient care, the health care team is complete.

Peripheral arterial disease in HIV-infected and uninfected women.

OBJECTIVE: Although HIV infection has been associated with increased risk of subclinical atherosclerosis and cardiovascular events, peripheral arterial disease (PAD) has not been assessed in HIV-infected patients. The objective of this study was to determine the prevalence of, and risk factors for, PAD using ankle-brachial index (ABI) measurement in HIV-infected and uninfected women. METHODS: ABI was determined for 335 participants in the Women's Interagency HIV Study (WIHS). A cross-sectional analysis was conducted to determine factors associated with high (>or=1.40) ABI. RESULTS: The prevalence of low ABI (or=1.40) was 6.9% (n=23). The prevalence of low ABI was too low to allow risk factor analysis. On multivariate analysis, factors associated with high ABI were current cigarette smoking [adjusted odds ratio (OR(adj)) 2.53, 95% confidence interval (CI) 0.99-6.43], being underweight (OR(adj) 11.0, 95% CI 1.61-75.63) and being overweight (OR(adj) 5.40, 95% CI 1.13-25.89). CONCLUSIONS: Although the prevalence of ABI or=1.40 was unexpectedly high. Further studies are indicated to determine the clinical significance of high ABI and its relation to the risk of cardiovascular events in HIV-infected women.

Care of women infected with the human immunodeficiency virus.

OBJECTIVE: --To review current knowledge regarding human immunodeficiency virus (HIV) infection in women and to derive from that data standards of care. DATA SOURCES: --Selective review of pertinent articles addressing cervical disease, pelvic inflammatory disease, sexually transmitted diseases, contraception, and pregnancy in HIV-infected women. A computer-assisted search was used to identify relevant articles on pharmacokinetics of drugs in women and oral contraceptive--drug interactions. DATA EXTRACTION: --Pertinent data were abstracted from case-control, cohort studies, clinical trials, and pharmacokinetic studies. DATA SYNTHESIS: --Few studies have been performed to define the clinical course of HIV infection in women. Gender-specific manifestations, such as cervical neoplasia, pelvic inflammatory disease, and vaginal moniliasis, appear to pursue a more aggressive course in HIV-infected women. Little is known about the pharmacokinetics of drugs for HIV and related infections. Oral contraceptives may alter the metabolism of some drugs used in HIV-infected women. An approach to the routine treatment of HIV-infected women is summarized. CONCLUSIONS: --Little is currently known regarding the natural course of HIV infection in women. Women infected with HIV should be followed up frequently with specific attention paid to the reproductive system. Additional studies should be conducted to determine the impact of HIV on gender-specific diseases.

Clinical manifestations and therapy of Isospora belli infection in patients with the acquired immunodeficiency syndrome.

Isospora belli has recently been recognized as an opportunistic protozoan pathogen in patients with the acquired immunodeficiency syndrome (AIDS). Although I. belli rarely causes diarrhea in patients with AIDS in the United States, we have documented isosporiasis in 15 percent (20 of 131) of such patients in Haiti. The infection was associated with chronic watery diarrhea and weight loss that was clinically indistinguishable from disease caused by the related coccidia cryptosporidium. No demographic or laboratory data distinguished the patients with AIDS and isosporiasis from those with either cryptosporidiosis or other opportunistic infections. Neither I. belli nor cryptosporidium was detected in stool samples from 170 healthy siblings, friends, and spouses of the patients with AIDS. In all patients with isosporiasis, diarrhea stopped within two days of the beginning of treatment with oral trimethoprim-sulfamethoxazole. Recurrent symptomatic isosporiasis developed in 47 percent of the patients, but it also responded promptly to therapy with trimethoprim-sulfamethoxazole. We conclude that isosporiasis is common in Haitian patients with AIDS, and that it responds to therapy with trimethoprim-sulfamethoxazole but is associated with a high rate of recurrence.

Health-related quality of life of HIV-infected women: evidence for the reliability, validity and responsiveness of the Medical Outcomes Study Short-Form 20.

The purpose of this study was to assess the reliability, validity and responsiveness of a health-related quality of life (HRQOL) instrument, the Medical Outcomes Short-Form 20-Item General Health Survey (MOS SF-20), in a sample of women with the human immunodeficiency virus (HIV). Longitudinal data were collected on 202 HIV-infected women without AIDS who were receiving care at Kings County Hospital or SUNY Health Sciences Center, Brooklyn, New York. Internal consistency results showed acceptable reliability for the four multi-item MOS scales (role function, physical function, general health perceptions and mental health). Symptomatic patients and patients with lower Karnofsky Performance Status (KPS) ratings reported lower HRQOL than those who were asymptomatic or who had higher KPS scores. Patients who were older, unemployed or who had a history of injection drug use (IDU) also reported lower HRQOL than those who were younger, employed or who had no drug use history. Adjusted mean scores on the MOS role and physical functioning scales proved sensitive to differences in clinical status over time. The MOS SF-20 is a reliable and valid instrument of HRQOL for women with HIV infection. Its sensitivity to differences in clinical status over time suggest that it may be useful as an HRQOL indicator for HIV/AIDS clinical trials.

Incidence and risk factors for heterosexually acquired HIV in an inner-city cohort of women: temporal association with pregnancy.

BACKGROUND: A growing proportion of AIDS cases in the United States are due to heterosexual transmission of HIV, particularly in women. The risk of heterosexually acquired HIV was prospectively studied in a cohort of inner-city women with no history of parenteral drug use. METHODS: Study participants were evaluated at 6-month intervals for the presence of HIV antibody, sexually transmitted diseases, self-reported sexual behavior, and drug use by self-report and urine screening. RESULTS: Of 449 initially HIV-negative women who were seen at least once in follow-up, 4 seroconverted to HIV, with a cumulative incidence of 2.4% at 30 months. Risk factors for HIV seroconversion included nonparenteral drug use (p < .02) and anal intercourse (p < .01). Sexually transmitted diseases were not associated with HIV, although the power to detect such an association was limited. In addition, 3 of 4 seroconverters became pregnant, yielding a rate of 55.5 pregnancies/100 person-years of follow-up compared with a rate of 11.1 pregnancies/100 person-years of follow-up in nonseroconverters (p < .03). CONCLUSION: The incident rate of heterosexually acquired HIV in this inner-city U.S. cohort of women who were not using parenteral drugs is comparable with that reported in some developing countries where heterosexually acquired HIV is endemic. Most seroconversions appeared related to risk behavior seen in association with nonparenteral drug use. The previously unreported association of incident HIV infection with pregnancy in this cohort may be related to either behavioral or biologic factors.

HIV infection, genital ulcer disease, and crack cocaine use among patients attending a clinic for sexually transmitted diseases.

BACKGROUND: Recently there has been a rise in genital ulcer disease (GUD) in urban minority heterosexuals in the United States. The impact of these increased GUD rates on HIV transmission patterns in this population is unknown. METHODS: Sexually transmitted disease (STD) diagnoses were correlated with HIV antibody status and risk factor history in 194 patients who consented to HIV testing at an STD clinic in central Brooklyn. RESULTS: Of 36 HIV-positive patients, 23 (64%) denied HIV risk factors other than heterosexual contact with persons of unknown HIV status. HIV antibody was associated with GUD (odds radio [OR] = 2.72, 95% confidence interval [CI] = 1.20-6.24), multiple concurrent STDs (OR = 2.51, 95% CI = 1.08-5.81), and a history of crack cocaine use (OR = 2.98, 95% CI = inexact-9.61). Crack use was also associated with GUD (OR = 15.15, 95% CI = 3.27-inexact) and multiple simultaneous STDs (OR = 13.87, 95% CI = 4.62-inexact). In a log-linear model analysis, HIV infection was independently associated with GUD and crack use. HIV infection, genital ulcer disease, and crack cocaine use were more common in women than men. CONCLUSIONS: The association between HIV infection and GUD seen here may be secondary to high-risk sexual behavior, which in turn may be partially attributable to crack cocaine use and drug-related prostitution. The high rate of coinfection with HIV and GUD raises a concern about the increased efficiency of sexual transmission of HIV in this population.