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Biomedical subjects

Howard Minkoff

Publications and source records attributed to Howard Minkoff.

At least 19 recordsLinked to original sources

Cervical shedding of HIV-1 RNA among women with low levels of viremia while receiving highly active antiretroviral therapy.

BACKGROUND: Among women with low or undetectable quantities of HIV-1 RNA in plasma, factors associated with genital HIV-1 RNA shedding, including choice of treatment regimen, are poorly characterized. METHODS: We measured HIV-1 RNA in cervical swab specimens obtained from participants in the Women's Interagency HIV Study who had concurrent plasma viral RNA levels <500 copies/mL, and we assessed factors associated with genital HIV shedding. The study was powered to determine the relative effects of antiretroviral protease inhibitors (PIs) versus nonnucleoside reverse transcriptase inhibitors (NNRTIs) on viral RNA shedding. RESULTS: Overall, 44 (15%) of 290 women had detectable HIV-1 RNA in cervical specimens. In the final multivariate model, shedding was independently associated with NNRTI (vs. PI) use (odds ratio [OR], 95% confidence interval [CI]: 2.24, 1.13 to 4.45) and illicit drug use (OR, 95% CI: 2.41, 0.96 to 5.69). CONCLUSIONS: This is the largest study to define risks for genital HIV-1 RNA shedding in women with low/undetectable plasma virus. Shedding in this population was common, and NNRTI-based highly active antiretroviral therapy (HAART) (vs. PI-based HAART) was associated with genital HIV shedding. Further study is required to determine the impact of these findings on transmission of HIV from mother to child or to sexual partners.

Adult↗

Vesicovaginal fistula associated with cytomegalovirus infection in an HIV-infected patient.

BACKGROUND: Cytomegalovirus (CMV) can cause multisystem disease in human immunodeficiency virus (HIV)-infected patients. An association with a vesicovaginal fistula has not previously been reported. CASE: An HIV-infected African-American female presented with back pain, swelling and paralysis of her lower extremities and continuous leakage of urine. Fundoscopic examination was typical of CMV retinitis. Doppler and CT studies showed bilateral deep vein thrombosis and bilateral pulmonary emboli, respectively. Anticoagulant therapy was started, and a Greenfield filter was placed. An examination under anesthesia and cystoscopy showed extensive vulvar and rectal condylomata, a large, necrotic, anterior vaginal mass, and a large vesicovaginal fistula. All necrotic tissue was resected and the biopsies taken identified CMV cytopathic effect. CONCLUSION: Vesicovaginal fistula in an immunocompromised individual may be a local manifestation of systemic CMV disease.

AIDS-Related Opportunistic Infections↗

Relationship between prevalent oral and cervical human papillomavirus infections in human immunodeficiency virus-positive and -negative women.

Human papillomavirus (HPV) is an etiologic agent for both oropharyngeal and cervical cancers, yet little is known about the interrelationship between oral and cervical HPV infections. Therefore, we compared the prevalences and type distributions of oral and cervical HPV infections and evaluated infection concordance in a cross-sectional study within the Women's Interagency HIV Study cohort. Oral rinse and cervical-vaginal lavage samples were concurrently collected from a convenience sample of 172 human immunodeficiency virus (HIV)-positive and 86 HIV-negative women. HPV genomic DNA was detected by PGMY09/11 L1 consensus primer PCR and type specified by reverse line blot hybridization for 37 HPV types and beta-globin. Only 26 of the 35 HPV types found to infect the cervix were also found within the oral cavity, and the type distribution for oral HPV infections appeared distinct from that for cervical infections (P<0.001). Oral HPV infections were less common than cervical infections for both HIV-positive (25.2% versus 76.9%, P<0.001) and HIV-negative (9.0% versus 44.9%, P<0.001) women. Oral HPV infections were more common among women with a cervical HPV infection than those without a cervical HPV infection (25.5% versus 7.9%, P=0.002). The majority of women (207; 93.7%) did not have simultaneous oral and cervical infections by the same HPV type; however, the number of women who did (14; 6.3%) was significantly greater than would be expected by chance (P=0.0002). Therefore, the oral and cervical reservoirs for HPV infection are likely not entirely independent of one another.

Cervix Uteri↗

The occurrence of vaginal infections among HIV-infected and high-risk HIV-uninfected women: longitudinal findings of the women's interagency HIV study.

OBJECTIVES: To evaluate changes over time in rates of bacterial vaginosis (BV), trichomoniasis (TV), and yeast vaginitis (YV) among HIV-infected and similar HIV-uninfected women. METHODS: Two thousand fifty-six HIV-infected women and 554 HIV-uninfected women were evaluated semiannually from 1994 until March 2003 in a prospective cohort study. BV was diagnosed by Gram stain, TV by wet mount, and YV by symptoms with microscopically visible hyphae or positive culture. Trends were assessed using Poisson models. RESULTS: At baseline, BV was present in 42.8% and 47.0% of HIV-infected and uninfected women (P = 0.21), TV in 6.1% and 7.8% (P = 0.17), and YV in 10.0% and 3.8% (P < 0.001). Over time, rates of BV and TV decreased significantly in both groups, whereas rates of YV declined only among HIV-infected women. Risk of BV was not associated with HIV status, whereas HIV-infected women had a lower risk of TV. Highly active antiretroviral therapy (HAART) use was associated with decreased risk of all 3 infections. CONCLUSIONS: : Declines in BV, TV, and YV represent decreased morbidity for HIV-infected women and, potentially, decreased risk of transmission of HIV, because each has been associated with increased genital detection of HIV.

Cohort Studies↗

The association of serum ferritin and transferrin receptor concentrations with mortality in women with human immunodeficiency virus infection.

BACKGROUND AND OBJECTIVES: Whether degree of iron stores influences progression of human immunodeficiency virus (HIV) disease is controversial. We studied the relationship of indirect measures of iron stores with mortality in highly active antiretroviral therapy (HAART)-naive participants from the Women's Interagency HIV Study. DESIGN AND METHODS: One hundred and fifty-eight HIV-infected women who died before July 1996 were individually matched by CD4+ cell count (within +/- 50 cells/mL) and HIV RNA level (within +/- 0.50 log10 copies/mL) to 154 controls. Serum ferritin and transferrin receptor concentrations were measured in 151 pairs of women. Results. Using multivariable conditional logistic regression models that were adjusted for self-reported antiretroviral therapy use, age, smoking status, ethnicity, hemoglobin concentration, C-reactive protein and aspartate amino transferase, a log10 increase in baseline serum ferritin concentration was associated with a 1.67-fold increase in the odds of death (95% CI: 0.98, 2.86) and a one-unit decrease in transferrin receptor to log10 ferritin ratio was associated with a 1.12-fold (95% CI: 1.01, 1.23) increase in the odds of death. INTERPRETATIONS AND CONCLUSIONS: In this study, higher indirect measures of iron status were associated with reduced survival among HAART-naive HIV-infected women. Additional prospective studies with data on direct measures of iron status along with randomized trials are needed to elucidate the current equipoise over whether iron supplementation is beneficial by preventing anemia or harmful by increasing iron stores in HIV-infected women.

CD4 Lymphocyte Count↗

Association of cigarette smoking with HIV prognosis among women in the HAART era: a report from the women's interagency HIV study.

OBJECTIVE: We assessed the association of cigarette smoking with the effectiveness of highly active antiretroviral therapy (HAART) among low-income women. METHODS: Data were analyzed from the Women's Interagency HIV Study, a multisite longitudinal study up to 7.9 years for 924 women representing 72% of all women who initiated HAART between July 1, 1995, and September 30, 2003. RESULTS: When Cox's regression was used after control for age, race, hepatitis C infection, illicit drug use, previous antiretroviral therapy, and previous AIDS, smokers on HAART had poorer viral responses (hazard ratio [HR]=0.79; 95% confidence interval [CI]=0.67, 0.93) and poorer immunologic response (HR=0.85; 95% CI=0.73, 0.99). A greater risk of virologic rebound (HR=1.39; 95% CI=1.06, 1.69) and more frequent immunologic failure (HR=1.52; 95% CI=1.18, 1.96) were also observed among smokers. There was a higher risk of death (HR=1.53; 95% CI=1.08, 2.19) and a higher risk of developing AIDS (HR=1.36; 95% CI=1.07, 1.72) but no significant difference between smokers and nonsmokers in the risk of death due to AIDS. CONCLUSIONS: Some of the benefits provided by HAART are negated in cigarette smokers.

Adolescent↗

Herpes simplex virus infection in women in the WIHS: epidemiology and effect of antiretroviral therapy on clinical manifestations.

OBJECTIVE: To determine the prevalence of infection with herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) among women with and at high risk for HIV infection, and to evaluate the effect of HAART on the recurrence of genital lesions. METHODS: We evaluated the epidemiology and clinical manifestations associated with HSV-1 and HSV-2 among 1796 HIV-infected and 476 HIV-uninfected women enrolled in a multisite cohort study. Serum antibodies to HSV-1 and HSV-2 at baseline and self-reported history of genital herpes, reports of recent genital sores and presence of genital ulcers on examination, and use of HAART regimen at each study visit were analyzed. RESULTS: Reactivity to HSV-1 only and HSV-2 only was detected in 18% and 20% of HIV-infected, and in 28% and 18% of HIV-uninfected participants respectively; 58% of HIV-infected women and 45% of HIV-uninfected women were seropositive for both HSV types. Reactivity to HSV-2 was associated with increasing age, more male sexual partners, earlier sexual debut, African-American race, Latina ethnicity, less education and lower income. HIV-uninfected women reported significantly fewer genital sores than HIV-infected women who had used HAART for at least 1 year and had optimal CD4 cell gain and viral suppression (adjusted odds ratio (OR), 0.19; 95% confidence interval (CI), 0.13-0.28). CONCLUSION: Use of HAART and subsequent immune recovery does not completely eliminate the effect of HIV infection on genital lesions among women with concurrent HSV-2 infection.

Adolescent↗

Aging and HIV infection.

With the advent of highly active antiretroviral therapy (HAART) in mid-1995, the prognosis for HIV-infected individuals has brightened dramatically. However, the conjunction of potent antiviral therapy and longer life expectancy may engender a variety of health risks that, heretofore, HIV specialists have not had to confront. The long-term effects of HIV infection itself and exposure to antiretroviral agents is unknown. Several aspects of aging, including psychiatric disease, neurocognitive impairment, and metabolic and hormonal disorders, may be influenced by chronic exposure to HIV and/or HIV therapeutics. In this paper, we discuss the health issues confronting HIV-infected older adults and areas for future research.

Aging↗

The ethics of cesarean section by choice.

In responding to patient requests for cesarean section, physicians must consider ethical principles. Obstetricians have autonomy and beneficence-based obligations to the mother, and the mother and the obstetrician have beneficence-based obligations to the fetus. Maternal autonomy is usually accepted as the most compelling ethical canon. However, the physician has a right to refuse requests. Thus, when a patient requests surgery, the physician may attempt to dissuade her and failing that either acquiesce or, feeling that professional conscience would not allow him/her to honor that request, refuse. Which choice is made should reflect the provider's believe about the strength of the supporting data. Given the need to recognize patient autonomy, to respect patient values even as one tries to motivate patients to work toward the highest health values, and to acknowledge women's primacy as fetal champions, a physician should be loathe to refuse unless the data regarding cesarean section by choice are wholly tilted away from maternal-child interests. If the data are in the realm of equipoise, even if not at the tipping point, discussing options, attempting to dissuade patients but ultimately acquiescing to their judgment would not be incompatible with obstetrical ethics.

Cesarean Section↗

Effects of HIV infection and its treatment on self-reported menstrual abnormalities in women.

OBJECTIVE: To describe menstrual abnormalities among women with HIV. METHODS: Women in a multicenter prospective cohort study of HIV natural history reported menstrual abnormalities every 6-months between October 1994 and September 2002. Logistic regression and Cox proportional-hazards models were applied. RESULTS: The prevalence and incidence of menstrual abnormalities were <20%. HIV serostatus was not associated with prevalent menstrual abnormalities, but in HIV-seropositive women, higher CD4 counts were associated with fewer problems: compared with women with CD4 counts <200/mm3, in women with counts 200-500/mm3, odds ratio (OR) for amenorrhea was 0.55, p = 0.02, and for oligomenorrhea was 0.54, p = 0.0003; for women with counts >500/mm3, OR for amenorrhea was 0.67, p = 0.14, and for oligomenorrhea was 0.55, p = 0.001. HIV serostatus was not associated with incident abnormalities. Highly active anti-retroviral therapy (HAART) use was not associated with prevalent abnormalities, but both HAART use and higher CD4 counts were linked to lower rates of incident menstrual problems. CONCLUSIONS: Compared with seronegative women, HIV-seropositive women are at increased risk for some menstrual changes, although the absolute frequency of most abnormalities is low. Higher CD4 counts and HAART protect against incident abnormalities.

Adult↗

Use of prenatal care by Hispanic women after welfare reform.

OBJECTIVE: The 1996 Personal Responsibility Work Opportunity Reconciliation Act (PRWORA, "welfare reform") changed immigrants' eligibility for publicly funded services such as Medicaid. However, implementation of the PRWORA varied by state. Florida implemented the eligibility restrictions, while California and New York preserved eligibility. Our objective was to compare the effect of state of residence and immigration status on use of prenatal care among Hispanic women in the period following the enactment of PRWORA. METHODS: In 1999-2001, we interviewed 3,242 postpartum Hispanic women in California, Florida, and New York. The dependent variable was use of prenatal care, dichotomized as adequate (initiated during the first trimester and > or = 6 visits, referent) or inadequate (initiated during the first trimester and < 6 prenatal visits or initiated after the first trimester). The primary independent variables were state of residence and maternal immigration status (U.S.-born citizens in New York, reference group). RESULTS: Thirteen percent of women were U.S.-born citizens, 8% were foreign-born citizens, 15% were documented immigrants, and 64% were undocumented immigrants. In Florida, women in all immigration subgroups were 2-4 times more likely to make inadequate use of prenatal care than U.S.-born citizens in New York. Documented immigrant women in New York were 90% more likely to make inadequate use of prenatal care than U.S.-born citizens in New York. CONCLUSION: Among Hispanic women in California, Florida, and New York, the state of residence, a measure of PRWORA policy changes, was associated with use of prenatal care. LEVEL OF EVIDENCE: II-2.

Adolescent↗

Relationship of pregnancy to human papillomavirus among human immunodeficiency virus-infected women.

OBJECTIVE: Because parity is a reported risk factor for cervical cancer, we sought to estimate the effects of pregnancy on the prevalence, incident detection, and copy number of human papillomavirus (HPV) among human immunodeficiency virus (HIV)-infected women, patients at high risk for cervical cancer. METHODS: Human immunodeficiency virus-infected women who had a pregnancy in the Women's Interagency HIV Study (n = 178) and the Women and Infants Transmission Study (n = 450) underwent serial type-specific HPV DNA testing using MY09/MY11 polymerase chain reaction. During pregnancy and during the prepregnancy and postpregnancy periods, we assessed HPV prevalence, incident detection, and HPV copy number (estimated using hybridization signal strength) of both oncogenic and nononcogenic HPV. All binary-regression analyses incorporated generalized estimating equations to address the repeated observations of the same women over time, and were further adjusted for parity, gestational age, smoking, antiretroviral use, number of lifetime sexual partners, and oral contraceptive use. RESULTS: The prevalence and copy number of oncogenic and nononcogenic HPV did not significantly differ between pregnancy and either the prepregnancy or postpregnancy periods. Incident HPV detection was significantly lower for both oncogenic and nononcogenic HPV during pregnancy compared with the postpregnancy period (relative risk 0.534, 95% confidence interval 0.390-0.732, P < .001 and relative risk 0.577, 95% confidence interval 0.428-0.779, P < .001, respectively), but not compared with the prepregnancy period CONCLUSION: Among HIV-infected women, the incident detection of HPV is lower during pregnancy compared with postpregnancy, while prevalence and copy number do no differ between pregnancy and either prepregnancy or postpregnancy. LEVEL OF EVIDENCE: II-3.

AIDS-Related Opportunistic Infections↗

Serological detection of human papillomavirus type 16 infection in human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women.

Serial measurement of antibodies has not been used to provide evidence of active viral replication of human papillomavirus (HPV). Serum specimens from sequential study visits contributed by 642 human immunodeficiency virus (HIV)-positive and 116 HIV-negative participants enrolled in the Women's Interagency HIV Study were used to detect significant rises in HPV type 16 (HPV-16) antibody levels. Factors associated with a significant rise were identified using multivariable logistic regression models with generalized estimating equations. Among HIV-positive women, 8.3% of 1,997 pairs showed antibody rises, compared to 6.1% of 361 pairs among HIV-negative women (P = 0.191). For HIV-positive women, rises were associated with current (odds ratio [OR], 23.4; P < 0.001) or past (OR, 8.9; P < 0.001) HPV-16 infection relative to never being HPV-16 infected and with CD4+ cell counts (OR per 100-cell increase, 0.8; P < 0.001) but not with sexual behavior. For HIV-negative women, rises were associated with past (OR, 10.9; P = 0.033) HPV-16 infection relative to no HPV-16, current cigarette smoking (OR, 5.0; P = 0.029) relative to no smoking history, and having 6 to 10 lifetime sexual partners compared to 0 to 5 partners (OR, 9.9; P = 0.036). Serial measurement of HPV-16 serum antibodies is a useful tool for identifying active HPV-16 viral replication. Rises among HIV-positive women may more often result from reactivation of a latent HPV infection in the context of HIV-induced immunosuppression, while rises among HIV-negative women may more often result from reinfection with HPV.

Antibodies, Viral↗

The association of race, sociodemographic, and behavioral characteristics with response to highly active antiretroviral therapy in women.

OBJECTIVE: To determine the association of race with clinical and laboratory outcomes after initiation of highly active antiretroviral therapy (HAART) in HIV-1-infected women in the United States. STUDY DESIGN: Prospective cohort study. PARTICIPANTS: A total of 961 HIV-1-infected women participating in the Women's Interagency HIV Study initiating HAART between July 1, 1995 and September 30, 2003. RESULTS: Over a median of 5.1 years of follow-up, in univariate Cox regression analyses, white women were more likely than African American women to attain a virologic response (relative hazard [RH]=1.34, P=0.005), less likely to experience viral rebound (RH=0.76, P=0.051), and less likely to die (RH=0.63, P=0.040). There were no significant differences, however, among racial groups in outcomes after adjustment for pre-HAART CD4, HIV-1 RNA, history of AIDS-defining illness, age, antiretroviral therapy use, baseline HIV-1 exposure category, and post-HAART behavioral and clinical variables associated with poorer response (discontinuation of HAART, lower income, smoking, current drug use, and depression). Continuous HAART use and lack of depression differed by race and were the strongest predictors of favorable outcomes. CONCLUSION: No significant differences by race were found in virologic, immunologic, or clinical outcomes after adjustment for continued HAART use and depression. These findings suggest that strategies to enhance HAART continuation, including assessing pharmacogenetic influences that may result in greater toxicity and discontinuation rates, and treating depression can improve individual and population-based effects of treatment and potentially mitigate racial disparities in AIDS-related outcomes.

Adult↗

Hormonal contraceptive use and the effectiveness of highly active antiretroviral therapy.

The role of hormonal contraceptive use in the effectiveness of highly active antiretroviral therapy (HAART) was examined among participants in the Women's Interagency HIV Study who were followed from HAART initiation to 2001. Propensity score selection was used to match 77 hormonal contraceptive users with 77 nonusers on age, race, and pre-HAART CD4-positive T-lymphocyte (CD4+ cell) count and viral load. The authors compared hormonal contraceptive users and nonusers with regard to the CD4+ cell count and viral load responses to HAART upon initiation. Proportional hazards analyses were used to assess the effect of hormonal contraceptive use on times to increases in CD4+ cell count of 50 cells/mm(3) and 100 cells/mm(3) and achievement of an undetectable viral load. There were no statistically significant differences in CD4+ cell counts and log viral load responses by hormone use after HAART initiation, except in log viral load at the third visit after initiation (p = 0.047). Time-dependent hormonal contraceptive use was not a statistically significant predictor of achieving increases in CD4+ cell count of 50 cells/mm(3) and 100 cells/mm(3) or an undetectable viral load (p = 0.517, p = 0.751, and p = 0.218, respectively) after HAART initiation. In conclusion, the authors did not find substantial evidence that use of hormonal contraceptives strongly affected responses to HAART.

Adult↗