Robert H. Byers

Syphilis increases HIV viral load and decreases CD4 cell counts in HIV-infected patients with new syphilis infections.

Background: Syphilitic ulcers are known to facilitate the transmission of HIV infection, but the effect of syphilis infection on HIV viral loads and CD4 cell counts is poorly understood. Methods: We abstracted medical records for HIV-infected male syphilis patients seen at three clinics in San Francisco and Los Angeles from January 2001 to April 2003. We compared plasma HIV-RNA levels and CD4 cell counts during syphilis infection with those before syphilis infection and after syphilis treatment, using the Wilcoxon signed rank test. Results: Fifty-two HIV-infected men with primary or secondary syphilis had HIV viral load and CD4 cell count data available for analysis; 30 (58%) were receiving antiretroviral therapy. Viral loads were higher during syphilis compared with pre-syphilis levels by a mean of 0.22 RNA log10 copies/ml (P = 0.02) and were lower by a mean of −0.10 RNA log10 copies/ml (P = 0.52) after syphilis treatment. CD4 cell counts were lower during syphilis infection than before by a mean of −62 cells/mm3 (P = 0.04), and were higher by a mean of 33 cells/mm3 (P = 0.23) after syphilis treatment. Increases in the HIV viral load and reductions in the CD4 cell count were most substantial in men with secondary syphilis and those not receiving antiretroviral therapy. Conclusion: Syphilis infection was associated with significant increases in the HIV viral load and significant decreases in the CD4 cell count. The findings underscore the importance of preventing and promptly treating syphilis in HIV-infected individuals.

Trends in diseases reported on U.S. death certificates that mentioned HIV infection, 1987-1999.

Summary: To examine trends in the proportions of deaths with various diseases among deaths with HIV infection, we analyzed multiple‐cause death certificate data for all deaths in the United States from 1987 through 1999. Disease proportions were adjusted to control for demographic changes. Deaths reported with HIV infection increased from 15,331 in 1987 to 47,977 in 1995 and then decreased to 16,061 in 1999. Among these reported deaths, new trends during the period from 1995 through 1999 included decreases in the proportions with cytomegalovirus disease (from 6.8% to 2.8%), wasting/cachexia (9.8% to 6.8%), and dementia/encephalopathy (6.3% to 3.9%) and increases in the proportions with septicemia/septic shock (from 9.2% to 13.4%) and diseases of the liver (4.9% to 11.6%), kidney (6.3% to 9.1%), and heart (4.2% to 6.9%). Continuations of pre‐1995 trends included decreases in the proportions with nontuberculous mycobacteriosis (7.1% to 3.1%) and Kaposi sarcoma (5.3% to 2.6%). Advances in antiretroviral therapy probably caused deaths due to HIV infection to decrease after 1995. Consequently, the proportions of deaths with HIV that were caused by other conditions increased. Improved prophylaxis or treatment of some opportunistic infections could also have reduced the proportions of deaths with those diseases, whereas antiviral drug toxicity could have contributed to increases in the proportions with noninfectious organ diseases.

Performance Characteristics of a New Less Sensitive HIV-1 Enzyme Immunoassay for Use in Estimating HIV Seroincidence

Less sensitive (LS) HIV-1 enzyme immunoassays (EIAs) have significantly improved the quantity and quality of HIV surveillance data. The first LS-HIV-1 EIA, the Abbott 3A11-LS, provided reliable incidence data, but the assay required specialized equipment, and the lack of available reagents made testing difficult. This study evaluated the use of an alternate assay, a modified version of the Vironostika HIV-1 EIA (Vironostika-LS), to be used for LS testing. The Vironostika-LS has similar performance characteristics to the Abbott 3A11-LS with additional advantages. This 96-well formatted assay is commonly found in public health laboratories for routine HIV-1 testing and can be used with both serum and dried blood spot specimens. The estimated mean time from seroconversion (defined using a standardized optical density cutoff of 1.0) with the Vironostika-LS was 170 days (95% CI, 145-200 days). When the Vironostika-LS was applied to a matched serum set previously tested with the Abbott 3A11-LS, the Vironostika-LS accurately identified 97% of specimens with recent or long-standing HIV infection. The paper also reports Vironostika-LS quality control guidelines and the results from 3 rounds of proficiency testing.

Impact of zidovudine use on risk and risk factors for perinatal transmission of HIV

Objectives:To evaluate the impact of perinatal zidovudine use on the risk of perinatal transmission of HIV and to determine risk factors for transmission among women using perinatal zidovudine. Design:Prospective cohort study of 1533 children born to HIV-infected women between 1985 and 1995 in four US cities. Methods:The association of potential risk factors with perinatal HIV transmission was assessed with univariate and multivariate statistics. Results:The overall transmission risk was 18% [95% confidence interval (CI), 16–21]. Factors associated with transmission included membrane rupture > 4 h before delivery [relative risk (RR), 2.1; 95% CI, 1.6–2.7], gestational age < 37 weeks (RR, 1.8; 95% CI, 1.4–2.2), maternal CD4+ lymphocyte count < 500 × 106cells/l (RR, 1.7; 95% CI, 1.3–2.2), birthweight < 2500 g (RR, 1.7; 95% CI, 1.3–2.1), and antenatal and neonatal zidovudine use (RR, 0.6; 95% CI, 0.4–0.9). For infants exposed to zidovudine antenatally and neonatally, the transmission risk was 13% overall but was significantly lower following shorter duration of membrane rupture (7%) and term delivery (9%). The transmission risk declined from 22% before 1992 to 11% in 1995 (P < 0.001) in association with increasing zidovudine use and changes in other risk factors. Conclusions:Perinatal HIV transmission risk has declined with increasing perinatal zidovudine use and changes in other factors. Further reduction in transmission for women taking zidovudine may be possible by reducing the incidence of other potentially modifiable risk factors, such as long duration of membrane rupture and prematurity.

Relative Efficacy of Prevention Counseling With Rapid and Standard HIV Testing: A Randomized, Controlled Trial (RESPECT-2)

Background: Two risk-reduction counseling sessions can prevent sexually transmitted diseases (STDs); however, return rates for test results are low. Study: A randomized, controlled trial compared rapid HIV testing and counseling in 1 visit with standard HIV testing and counseling in 2 visits. Main outcomes were STDs (gonorrhea, chlamydia, trichomoniasis, syphilis, HIV) within 12 months. Participants were 15- to 39-year-old STD clinic patients in Denver, Long Beach, and Newark. STD screening and questionnaires were administered every 3 months. Results: Counseling was completed by 1632 of 1648 (99.0%) of the rapid-test group and 1144 of 1649 (69.4%) of the standard-test group. By 12 months, STD was acquired by 19.1% of the rapid group and 17.1% of the standard group (relative risk [RR], 1.11; confidence interval [CI], 0.96–1.29). STD incidence was higher in the rapid-test group than in the standard-test group among men (RR, 1.34; CI, 1.06–1.70), men who had sex with men (RR, 1.86; 95% CI, 0.92–3.76), and persons with no STDs at enrollment (RR, 1.21; 95% CI, 0.99–1.48). Behavior was similar in both groups. Conclusions: Counseling with either test had similar effects on STD incidence. For some persons, counseling with standard testing may be more effective than counseling with rapid testing.

Trends in antiretroviral therapy use and survival rates for a large cohort of HIV-infected children and adolescents in the United States, 1989-2001.

Background:In the United States, HIV-infected children and adolescents are aging and using antiretroviral (ARV) therapy for extended periods of time. Objective:To assess trends in ARV use and long-term survival in an observational cohort of HIV-infected children and adolescents in the United States. Methods:The Pediatric Spectrum of HIV Disease Study (PSD) is a prospective chart review of more than 2000 HIV-infected children and adolescents. Patients were included in the analysis from enrollment until last follow-up. Results:Triple-ARV therapy use (for 6 months or more) increased from 27% to 66% during 1997 to 2001 (P < 0.0001, χ2 for trend). The proportion of patients receiving 3 or more sequential triple-therapy regimens also increased from 4% to 17% during 1997 to 2001 (P < 0.0001, χ2 for trend), however, and the durability of triple-therapy regimens decreased from 13 to 7 months from the first to third regimen. Survival rates for the 1997 to 2001 birth cohorts were significantly better than for the 1989 to 1993 and 1994 to 1996 cohorts (P < 0.0001). Conclusions:Survival rates in the PSD cohort have increased in association with triple-ARV therapy use. With continued changes in ARV regimens, effective modifications in ARV therapy and the sustainability of gains in survival need to be determined.

Influence of human immunodeficiency virus infection on pelvic inflammatory disease.

Objective To examine the influence of human immunodeficiency virus (HIV) infection on clinical and microbiologic characteristics of pelvic inflammatory disease (PID). Methods Forty-four HIV-infected women and 163 HIV noninfected women diagnosed with PID by standard case definition were evaluated by using clinical severity scores, transabdominal sonograms, and endometrial biopsies. After testing for bacterial infections, patients were prescribed antibiotics as recommended by the Centers for Disease Control and Prevention (CDC). Results Symptoms of PID and analgesic use before enrollment did not differ by HIV serostatus. More HIV-infected women had received antibiotics before enrollment (40.9% versus 27.2%, P = .08), a factor associated with milder signs regardless of serostatus. More HIV-infected women had sonographically diagnosed adnexal masses at enrollment (45.8% versus 27.1%, P = .08), a difference that yielded higher median severity scores (17.5 of 42 points versus 15 of 42 points, P = .07). However, those differences were not significant at the P < .05 level. Mycoplasma (50% versus 22%, P < .05) and streptococcus species (34% versus 17%, P < .05) were isolated more commonly from biopsies of HIV-infected women. Within 30 days after enrollment, HIV-infected women generally responded as well to therapy as HIV-noninfected women did, regardless of initial CD4 T-lymphocyte percentage. Conclusion Among women with acute PID, HIV infection was associated with more sonographically diagnosed adnexal masses. Clinical response to CDC-recommended antibiotics did not differ appreciably by serostatus. Mycoplasmas and streptococci were isolated more commonly from HIV-infected women, but those organisms also might be associated with PID in immunocompetent women.

Epidemiology of HIV/AIDS in children.

HIV infection has been a major cause of morbidity and mortality since the first cases of AIDS among children were reported in 1982 in the United States. Considerable advances, especially in the past 5 years, in the understanding of the pathogenesis, diagnosis, treatment, monitoring, and prevention of HIV infection in children have changed the rate of pediatric HIV infection in the United States. Efforts to maximally decrease perinatal HIV transmission in the United States are ongoing. Physicians must try to prevent HIV infection among women, especially adolescents.

HIV Type 1 Incidence Estimates by Detection of Recent Infection from a Cross-Sectional Sampling of Injection Drug Users in Bangkok: Use of the IgG Capture BED Enzyme Immunoassay

Development of serologic tests to detect recent HIV-1 infection has generated worldwide interest in applying this approach to estimate incidence. We previously devised an IgG-capture BED-EIA (or BED-CEIA) that detects increasing levels of anti-HIV IgG following seroconversion to identify recent infection and to estimate incidence among persons infected with diverse HIV-1 subtypes worldwide. Injection drug users (IDUs; n = 1969) were screened in 1996 for participation in a prospective cohort study. Serum specimens from 594 IDUs were HIV-1 seropositive (30.2%) and were tested with the BED-CEIA. The proportion of recent infections and estimated incidence by different epidemiological risk factors were compared with incidence data measured from the prospective cohort. Of 594 HIV-1-seropositive specimens, 113 (19%) were identified as recent infections. Overall, the estimated annual incidence among persons screened was 17.3%/year (95% CI, 12.8-24.2%/year) compared with 9.0%/year (95% CI, 6.7-11.9%/year) measured from the prospective cohort during the same time period. Estimated incidence was higher among younger aged and unemployed IDUs as well as among those who injected more frequently, confirming previously reported risk factors from this prospective cohort. As persons screened from a cross-sectional sampling probably have higher risk for HIV than selected uninfected individuals who choose to participate and receive risk reduction counseling in a longitudinal cohort study, use of this or other serologic testing strategies to identify populations with high incidence (such as for HIV vaccine trials) may overestimate incidence measured from prospective cohorts.

Prevention of HIV Infection in Street-Recruited Injection Drug Users

Background: Injection drug users (IDUs) and their sex partners account for an increasing proportion of new AIDS and HIV cases in the United States, but public debate and policy regarding the effectiveness of various HIV prevention programs for them must cite data from other countries, from non‐street‐recruited IDUs already in treatment, or other programs, and from infection rates for pathogens other than HIV. Methods: Participants were recruited from the street at six sites (Baltimore [Maryland], New York [two sites], Chicago [Illinois], San Jose [California], Los Angeles [California], and at a state womens correctional facility [Connecticut]), interviewed with a standard questionnaire, and located and reinterviewed at one or more follow‐up visits (mean, 7.8 months later). HIV serostatus and participation in various programs and behaviors that could reduce HIV infection risk were determined at each visit. Results: In all, 3773 participants were recruited from the street, and 2306 (61%) were located and interviewed subsequently. Of 3562 initial serum specimens, 520 (14.6%) were HIV‐seropositive; at subsequent assessment, 19 people, all from the East Coast and Chicago, had acquired HIV. Not using previously used needles was substantially protective against HIV acquisition (relative risk [RR], 0.29; 95% confidence interval [CI], 0.11‐0.80 ) and, in a multivariate model, was significantly associated with use of needle and syringe exchange programs (adjusted odds ratio [ORadj], 2.08; 95% CI, 1.15‐3.85). Similarly, reduction of injection frequency was very protective against seroconversion (RR, 0.33; 95% CI, 0.14‐0.80), and this behavior was strongly associated with participation in drug treatment programs (ORadj, 3.54; 95% CI, 2.50‐5.00). In a separate analysis, only 37.5% of study‐participants had sufficient new needles to meet their monthly demand. Conclusions: In this large multicity study of IDUs in the United States, several HIV prevention strategies appeared to be individually and partially effective; these results indicate the continued need for, and substantial gaps in, effective approaches to preventing HIV infection in drug users.