Biomedical subjects
Publications and source records attributed to L Solomon.
This article describes current epidemiologic trends in HIV infection in women worldwide and in the United States, the natural history of HIV infection in women as currently understood, clinical management of HIV-infected women in those areas in which it differs from men, and multiple issues relating to pregnancy and childbearing in HIV-infected women.
We compared Hybrid Capture, a new technique for detection of human papillomaviruses (HPV), with a PCR assay based on L1 consensus primers. By both methods, the HPV prevalence was higher in human immunodeficiency virus (HIV)-positive women than in HIV-negative women. PCR had a higher sensitivity (0.89 versus 0.48) but lower specificity (0.43 versus 0.93) for detection of Pap smear abnormalities, compared to Hybrid Capture. The higher intensity of hybridization signal by PCR was related to higher estimates of viral load by Hybrid Capture.
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The relationship between HIV testing history. HIV serostatus, and risk behaviors was examined to investigate factors associated with obtaining an HIV test, returning for results, or receiving multiple tests. Seven hundred and five volunteers for an HIV study were questioned about prior HIV testing, drug and sexual practices, and sociodemographic characteristics. Women who reported a prior HIV test were compared with those without a previous test, women who returned for test results were compared with those not returning; and women who reported multiple tests were compared with those having only one test. Seventy-five percent of the women reported a prior test; 12% had not returned for test results; 46% reported multiple tests. Women reporting higher levels of HIV risk behaviors were more likely to have been tested and to return for results. Injection drug use and having four or more sex partners were significantly associated with repeated HIV testing. Over one third of the women with substantial HIV risk practices had not been HIV tested or failed to obtain test results. Women who obtained multiple HIV tests were more likely to report high-risk practices in spite of having received risk counseling with repeated testing.
OBJECTIVE: To evaluate whether zidovudine treatment was accepted and used by pregnant women subsequent to the release of the results of a multicenter, randomized, placebo-controlled trial (AIDS Clinical Trial Group [ACTG] Protocol 076) that showed that zidovudine significantly reduced maternal-infant human immunodeficiency virus (HIV) type 1 transmission. DESIGN: Prospective study. SETTING: A community hospital with an integrated, multidisciplinary HIV-dedicated program located in an impoverished, HIV-endemic urban setting. PARTICIPANTS: All HIV-infected pregnant women identified after the release of the ACTG 076 results who were offered zidovudine therapy to reduce maternal-infant transmission. RESULTS: Only 49 of the 125 HIV-infected pregnant women delivering at our site during this study period were identified prenatally. Perinatal zidovudine therapy was chosen by 37 (75%) of 49 women. Women refusing zidovudine were more likely to report injection drug use as their HIV risk factor and to continue to use drugs during their pregnancy. Of women choosing zidovudine and delivering, 24 of 36 received all components of their elected therapy. The intrapartum dose was missed by 12 women, 4 of whom also missed their prescribed prenatal oral therapy. Lack of adherence to chosen therapy was associated with continued cocaine use during pregnancy. CONCLUSIONS: Zidovudine therapy to interrupt vertical transmission of HIV was not widely used by these HIV-infected pregnant women. Further studies evaluating factors affecting the acceptance and use of recently published public health recommendations are needed.
Human cytomegalovirus (CMV) encodes a unique serine proteinase that is required in the maturation of the viral capsid. The CMV proteinase can undergo autocatalytic activation and is subject to proteolytic self-inactivation. Mutant enzyme forms were prepared to eliminate the initial autoprocessing site and thus form an active single-chain protein for structure-function studies. Two mutants of CMV proteinase were cloned and expressed in Escherichia coli. The A143V mutant was a conservative substitution at the first internal cleavage site. The S132A mutant modified one of the triad of residues responsible for catalytic activity. Through the use of computer-controlled high-cell-density fermentations the mutant proteins were expressed in E. coli at approximately 170 mg/L as both soluble (approximately 40% of total) and inclusion-body forms (approximately 60% of total). The soluble enzyme was purified by standard methods; inclusion-body protein was isolated by standard methods after refolding and solubilization in guanidine or urea. Sedimentation equilibrium and sedimentation velocity analyses reveal that the enzyme undergoes concentration-dependent aggregation. It exhibits a monomer <==> dimer equilibrium (Kd = 1 microM) at low concentrations and remains dimeric at high concentrations (28 mg/ml). Differential scanning calorimetry data for protein thermal unfolding fit best to a non-two-state model with two components (Tm = 52.3 and 55.3 degrees C) which subsequently aggregate upon unfolding. Analysis of the short-UV circular dichroism spectra of protein forms resulting from expression as soluble molecules (not refolded) reveals that the two mutants have very similar secondary structures which comprise a mixed structural motif of 20% alpha-helix, 26% beta-sheet, and 53% random coil. Though soluble and active (A143V mutant only), CD analysis revealed that protein refolded from inclusion bodies did not exhibit spectra identical to that of protein expressed only in soluble form.
To examine the relationship between latent Mycobacterium tuberculosis infection and human immunodeficiency virus (HIV) disease progression, two studies were done among a cohort of HIV-infected injecting drug users. First, the decline in CD4 cell count after baseline tuberculin skin testing was prospectively compared for 37 tuberculin-positive (induration > or = 5 mm) and 284 tuberculin-negative (induration < or = 2 mm) persons. After adjustment for baseline immune function, the mean 6-month CD4 cell decline was not significantly different (34.5 vs. 45.6 cells, respectively, P = .14). Second, the plasma HIV burden at baseline skin testing was compared for 33 tuberculin-positive cases and 33 matched tuberculin-negative controls. HIV RNA was detected in 8 cases and 10 controls (odds ratio = 0.67, 95% confidence interval = 0.19-2.36). Among the 14 pairs with HIV detected in > or = 1 member, the HIV concentration was higher for the case in 4 and for the control in 10 (P = .18). These findings suggest that unlike active tuberculosis, latent M. tuberculosis infection does not hasten HIV progression.
Human immunodeficiency virus (HIV) infection and infective endocarditis are serious complications of injection drug use. To determine whether HIV infection may increase the risk of endocarditis beyond that associated with drug injection, we performed a nested case-control study among injecting drug users taking part in an ongoing cohort. We identified 26 participants with infective endocarditis between cohort enrollment (in 1988-1989) and June 1992, through reviews of medical records and death certificates. We matched each endocarditis case with up to five controls (N = 120) on enrollment date, race/ethnicity, and follow-up time. Data were taken from baseline and from the one follow-up visit: the last visit before the endocarditis occurred for cases and the closest visit (+/- 3 months) for controls. We used conditional logistic regression to quantify the association between HIV serostatus at follow-up and subsequent endocarditis, after adjusting for a history of endocarditis or sepsis before enrollment, injection duration, current injection frequency, and a recent history of abscess at injection sites. Among current injectors at follow-up, the adjusted odds ratio (OR) of developing endocarditis for HIV-seropositive subjects with > or = 350 CD4 cells per microliter, compared with HIV-seronegative subjects, was 2.31 [95% confidence interval (CI) = 0.61-8.78]; the corresponding OR for HIV-seropositive subjects with < 350 CD4 cells per microliter was 8.31 (95% CI = 1.23-56.37). These data indicate that HIV-related immunodeficiency may independently increase the risk of infective endocarditis among injecting drug users.
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OBJECTIVE: To measure the temporal trends in the incidence of infection with human immunodeficiency virus in a cohort of injecting drug users in Baltimore, Md, between 1988 and 1992. DESIGN: Study subjects were screened for antibodies to human immunodeficiency virus by enzyme-linked immunosorbent assay and confirmed with Western blot. They were followed up at 6-month intervals with repeated serologic screening and comprehensive interviews for human immunodeficiency virus risk factors. SETTING: Special study clinic. PARTICIPANTS: A cohort of 2960 participants were recruited and screened between February 1988 and March 1989. Recruitment criteria included an age of 18 years or older, a history of illicit drug injection since 1978, and the absence of the acquired immunodeficiency syndrome; subjects were subsequently tested for human immunodeficiency virus antibodies. Most subjects (85%) were not receiving methadone treatment at baseline and were recruited by word of mouth. MAIN OUTCOME MEASURE: Human immunodeficiency virus seroconversion. RESULTS: Of the 2247 seronegative participants at baseline, 1532 were followed up, and 188 (12.3%) had seroconverted by December 1992. The incidence of human immunodeficiency virus infection over time among users declined somewhat, especially among women; the overall incidence was 1.90 per 100 person-semesters, or 3.80% annually. The incidence, adjusted for gender, was higher in younger (< 35 years) than older (> or = 35 years) subjects (relative incidence, 1.75; 95% confidence interval, 1.29 to 2.38) and in women compared with men, adjusted for age (relative incidence, 1.29; 95% confidence interval, 0.95 to 1.80). The relative incidence among active compared with inactive drug users adjusted for age and gender was 1.58 (95% confidence interval, 1.06 to 2.35). CONCLUSIONS: Although the incidence of human immunodeficiency virus infection in this cohort of injecting drug users in Baltimore declined somewhat during the 4 years of follow-up, especially among women, the persistent annual incidence of nearly 4% during 3 1/2 to 4 1/2 years of observation suggests the need for additional strategies for prevention of infection, especially among those who continue injecting drugs. Newer methods of prevention, such as provision of sterile injection equipment, an effective human immunodeficiency virus vaccine, and wider availability of effective treatment or prevention of drug addiction, are urgently needed in these high-risk populations.
Injection drug users are at high risk for hepatitis C virus (HCV) infection. In Baltimore, Maryland, the prevalence of anti-HCV is greater among injection drug users who are black, human immunodeficiency virus (HIV) infected, have injected longer, have injected more frequently, and have injected cocaine than among other injection drug users. HCV infection occurs quickly after the initiation of injecting illicit drugs, with 78% of study participants anti-HCV positive after 2 years of injecting. The prevalence of anti-HCV among injection drug users does not appear to be related to socioeconomic factors or sexual practices. Some injection drug users remain free of anti-HCV even after years of injecting and serologic evidence of other bloodborne pathogens. Some of these injection drug users have HCV infection, demonstrated by HCV RNA in their sera. However, the basis for viral persistence in the absence of anti-HCV and for the absence of HCV infection in long-term drug users is not known. Further studies are indicated to determine the mechanism or mechanisms for the absence of anti-HCV in persons exposed to the virus, because the biologic basis for this condition may elucidate the elements missing in the immune response of the majority of HCV-exposed persons who acquire persistent infection. In addition, interventions to prevent HCV infections should be applied in populations at risk for injection drug use early or before drug use begins.
Recent epidemiologic studies of the cognitive performance of injecting drug users have demonstrated the need to establish appropriate test norms for this population. This report provides normative data from a group of 150 injecting drug users on a battery of standardized tests of cognitive performance stratified by age group (range 20 to 49 years) and educational level (mean 11.6, standard deviation 2.0). The analysis also includes estimation of partial correlations between neuropsychologic test scores and age and education. The analysis demonstrates that age and education are important determinants of performance for several of these tests, and provides norms that may be of use as a reference for clinical evaluation and research in drug user populations.
BACKGROUND AND METHODS: To compare rates of decline of CD4+ lymphocytes among human immunodeficiency virus-positive homosexual men and injecting drug users, we followed up prevalent human immunodeficiency virus-positive homosexual men and current or former injecting drug users from February 1988 through August 1991. Subjects were free of acquired immunodeficiency syndrome at study entry and had semiannual clinical and laboratory evaluation, including measurement of T-cell subsets, under common protocols. Initial levels and rates of change of CD4+ lymphocyte counts were compared according to cohort membership and clinical progression, defined by the development of thrush or an acquired immunodeficiency syndrome--defining illness. Median follow-up was 30 months for both cohorts. RESULTS: At study entry, homosexual men had lower absolute numbers of circulating CD4+ lymphocytes than did injecting drug users (459/microL [0.46 x 10(9)/L] vs 509/microL, respectively). During follow-up, homosexual men exhibited a faster decline in CD4+ lymphocyte counts as well as more frequent development of HIV-related symptoms (thrush or acquired immunodeficiency syndrome). In both cohorts, initial levels of CD4+ lymphocytes and rates of decline in these cells were strongly associated with progression of disease, defined as remaining asymptomatic, onset of thrush, or onset of acquired immunodeficiency syndrome. Once homosexual men and injecting drug users were stratified by disease progression, their initial levels and rates of decline of CD4+ lymphocyte counts were similar. Thus, crude differences between the two study groups largely resulted from differences in development of clinical symptoms. CONCLUSIONS: In these cohorts of homosexual men and injecting drug users, clinical outcome was much more important than risk group membership in determining changes in CD4+ lymphocyte numbers. The close similarity between the groups also suggests that drug use, ethnicity, and socioeconomic status play a minor role in the progression of human immunodeficiency virus infection.
OBJECTIVE: To compare occurrence of clinical symptoms, physical examination findings and hematologic variables in male and female HIV-seropositive injecting drug users (IDU) with similar CD4+ lymphocyte counts. METHOD: We interviewed and examined 118 female and 444 male AIDS-free HIV-seropositive IDU for clinical signs and symptoms. HIV serology and T-lymphocyte subset evaluations were performed. Comparisons were analyzed by Mantel-Haenszel procedures. RESULTS: In this population, median age for men was 35 years versus 33 years for women; median CD4 cell count was 490 x 10(6)/l for men versus 480 x 10(6)/l for women. The overall frequency of oral candidiasis increased as CD4 cell count decreased, but did not vary by sex. Recent history of genital herpes was more frequent (P < 0.05) in women than men, but this difference was not significant on physical examination. Symptoms of diarrhea, fatigue, weight loss, shortness of breath, presence of enlarged posterior cervical lymph nodes did not vary by CD4 cell count or sex, and no strong interactions were evident. Although absolute values of hematocrit were higher (P < 0.001) and platelet count lower (P < 0.001) in HIV-seropositive men than women, distributions of hematocrit and platelet count by sex were similar for HIV-seropositive participants and HIV-seronegative controls. CONCLUSION: Our data on IDU prior to a diagnosis of AIDS suggest that constitutional signs and symptoms are generally similar among men and women early in HIV infection. Additional follow-up is needed to determine whether differential rates of signs and symptoms by sex appear with progression of HIV infection.
To examine the risk factors for the first episode of bacterial pneumonia among human immunodeficiency virus (HIV)-seropositive injection drug users (IDUs), medical record review was performed on IDUs participating in a cohort study from January 1988 to June 30, 1992. HIV-seropositive IDUs with a first episode of bacterial pneumonia (n = 40) were matched with up to five HIV-seropositive control subjects without bacterial pneumonia (n = 197) by date of entry (+/- 3 mo) and length of follow-up. Odds ratios (OR) were estimated using conditional logistic regression. The incidence of bacterial pneumonia was 1.93 in 100 person-years in HIV seropositive and 0.45 in 100 person-years in HIV seronegative subjects (relative incidence = 4.3; 95% CI 2.4 to 7.5). In univariate analyses, CD4 lymphocyte count < 200 cells/microliters previous episode of Pneumocystis carinii pneumonia (PCP), age between 30 and 40 yr and smoking illicit drugs (marijuana, cocaine, or crack) were associated with bacterial pneumonia. Cigarette smoking was associated with an increased odds of bacterial pneumonia (OR = 2.0), but this was not statistically significant because it was nearly universal in this cohort. In multivariate analysis, CD4 < 200 cells/microliters (OR = 6.75, 95% CI 2.13 to 21.42) and smoking illicit drugs (OR = 2.24, 95% CI 1.03 to 4.89) remained significantly associated with bacterial pneumonia. The odds ratio for cigarette smoking in the final model remained at 2.08 but was still not significant (95% CI 0.49 to 8.70). Smoking illicit drugs had the strongest effect on risk of bacterial pneumonia among HIV-seropositive IDUs with a previous history of PCP (OR = 22.94; 95% CI 2.18 to 241.10).
Salivary amylase is known to bind specifically to several species of oral streptococci. To assess the importance of this interaction in bacterial colonization of the oral cavity, we determined the proportion and identity of amylase-binding bacteria (ABB) in dental plaque of humans and various salivary amylase-secreting and non-secreting mammalian species. The numbers of ABB in undisturbed plaque collected over time from tooth surfaces of six human volunteers or from 14 other mammalian species were determined by means of a replicating assay. The mean proportion of ABB cultured aerobically from human teeth at 2 h was 10.5% (SD 10), at 8 h 7.9% (8), at 24 h 13% (11), and at 48 h 12% (9). The mean proportion of anaerobically cultured ABB found at 2 h was 3% (SD 4), at 8 h 5% (5), at 24 h 12% (9), and at 48 h 16% (12). Amylase-binding bacteria cultured from these samples resembled Streptococcus mitis, Streptococcus gordonii, Streptococcus salivarius, Streptococcus crista, or unidentified streptococci. In addition, only animals exhibiting salivary amylase activity in their saliva harbored ABB (ranging from 2 to 31% of the total flora), with the exception of the pig, where no ABB were found to colonize, despite considerable amylase activity in saliva. Only strains resembling S. mitis and S. salivarius and unspeciated strains were isolated from these mammals. These results suggest that amylase-binding streptococci are the predominant ABB in human plaque, and their numbers generally increase as plaque develops. Since ABB colonized only the oral cavities of hosts demonstrating salivary amylase activity, the ability to bind amylase may play an important role in oral colonization by these bacteria.
The Washington, DC City Council authorized a pilot syringe exchange program to operate for only 60 days at a single drug abuse treatment facility in the District. Only adults on the waiting list for treatment were eligible (n = 467). Of the 33 who enrolled, median duration of drug injection was 18 years. Twenty-seven participants denied needle sharing. Of 209 needles distributed, 69% were returned. Low enrollment might have been due to restrictive entry criteria, inconvenient location, incorrect syringe size, and attitudes of treatment staff. For future efforts to have a public health impact, wider accessibility will be needed.
OBJECTIVES: Data from 538 women in a cohort study recruited in 1988-1989 were analyzed to determined whether trading sex for drugs or money was independently associated with human immunodeficiency virus (HIV) seroprevalence in a population of female intravenous drug users. METHODS: The women were grouped according to the number of partners with whom they reported trading sex for drugs or money during the previous 10 years: none, 1 through 49 (low), or 50 or more (high); the prevalence of HIV seropositivity in the three groups was 23.2%, 23.7%, and 47.6%, respectively. Logistic regression was used to compare the low- and high-trade groups separately with the group that reported no trading. RESULTS: Low trading was not associated with seroprevalent HIV infection. In a multivariate model, high trading (compared with no trading) was significantly associated with HIV seropositivity after adjustment for cocaine use, history of sexually transmitted diseases, and duration of intravenous drug use. CONCLUSIONS: These data indicate that, among intravenous drug-using women, high levels of trading sex for drugs or money were independently associated with HIV infection. This group needs to be targeted for further intensive intervention.