Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association最新文献

Objectives: To document the HIV and STD infection rates among clients of female (CFP) and clients of male prostitutes (CMP) and to identify the risk factors for HIV among CFP and CMP.

Methods: Structured interviews were conducted with 82 CMP and 69 CFP in 1990 and 1991 in Atlanta, Georgia, U.S.A. Blood samples were tested for HIV, syphilis, and hepatitis B.

Results: The HIV-positive rate was 36.6% among CMP and 2.9% among CFP. Syphilis seromarkers were found in 15.9% of CMP and 10.1% of CFP; hepatitis B seromarkers were identified in 58.0% of CMP and 24.6% of CFP. Key risk factors for HIV among CMP included serologic history of syphilis, serologic history of hepatitis B, receptive anal sex with a male prostitute, ever injecting drugs, ever using crack cocaine, and little education. CFP had no significant risk factors for HIV in the logistic analysis.

Conclusions: Several studies have focused on risk factors for HIV among female and male prostitutes; however, research on their clients has been limited. Although HIV infection rates among CFP are relatively low, their infection rate for syphilis and hepatitis warrants serious health education efforts. Even more critical are harm-reduction programs targeting CMP. Generic health and HIV risk reduction messages on heterosexual transmission might be insufficient.

Non-syncytium-inducing (NSI) variants seem to be more readily transmitted than syncytium-inducing (SI) variants, and the switch from NSI to SI during HIV-1 infection seems to be a key determinant to the evolution of AIDS. We investigated eventual differences in the SI capacity on MT-2 cells according to genetic subtypes of HIV-1 and correlated this observations with CD4 counts and duration of HIV infection. In total, 86 patients, most with known date of HIV contamination and infected with different genetic subtypes, have been studied: 11 subtype A, 46 subtype B, 22 subtype C, and 7 subtype E. Multivariate analysis used a Cox's proportional hazards regression. The number and percentage of patients infected with an SI strain were as follows: 3 of 11 (27%) for subtype A, 15 of 46 (33%) for subtype B, 0 of 22 (0%) for subtype C, and 5 of 7 (71%) for subtype E. After adjustment for time after seroconversion and CD4 counts, significantly fewer SI variants were observed in patients infected with subtype C (p < .002) and it was found that subjects infected with subtype E had a higher risk of being infected with an SI strain (rate ratio [RR] = 12.39%; 95% confidence interval [CI] 1.55-98.67; p < .001). Most of the subtype E-infected patients from our study switched from an NSI to SI phenotype early after seroconversion (<4 years). To predict the in vitro presence of SI variants, we scanned V3-loop sequences for mutations at positions 11 and/or 25. Overall, 54 of 55 (98.2%) NSI strains in vitro were predicted NSI, and only 4 of 12 (33.3%) of SI viruses were predicted SI. For patients in whom a switch from an NSI to an SI virus was observed, the SI phenotype could be detected earlier in vitro than by the corresponding V3-loop sequence. No SI strains were observed among patients infected with subtype C; however, longer follow-up is needed to see whether the appearance of SI variants in subtype E or the absence of SI variants in subtype C-infected patients is also associated respectively with a faster or slower progression to AIDS as described for subtype B.

Objective: To determine obstetric and neonatal outcomes in a cohort of HIV-infected pregnant women and to assess whether HIV-related immunosuppression increases the risk of adverse outcomes of pregnancy.

Methods: Between 1989 and 1994, interview, physical examination, laboratory, and medical record data were prospectively collected from HIV-infected pregnant women and on their newborns. Factors associated with adverse pregnancy outcome and HIV disease status were correlated with pregnancy outcome using logistic regression analysis.

Results: 634 women delivered after 24 weeks of gestation. Preterm birth, low birth weight, and small-for-gestational-age neonates occurred in 20.5%, 18.9%, and 24.0% of pregnancies, respectively. Factors associated with low birth weight were CD4 percentage <14%, history of adverse pregnancy outcome, pediatric HIV infection, bleeding during pregnancy, and Trichomonas infection. Preterm birth was associated with CD4 percentage <14%, a history of adverse pregnancy outcome, and bleeding during pregnancy. Being small for gestational age was associated with maternal hard drug use during pregnancy, Trichomonas infection, history of adverse pregnancy outcome, and hypertension.

Conclusions: Adverse pregnancy outcomes are common for HIV-infected women and are associated with low maternal CD4 percentage and pediatric HIV infection. Preterm birth, low birth weight, and small-for-gestational-age ranking, however, are also associated with previously recognized sociodemographic and obstetric factors that are not unique to HIV infection.

Retroviruses including HIV-1 integrates a DNA copy of their RNA genome into cellular DNA of the infected cell. This reaction, essential and unique to replication of retroviruses, is mediated by the viral enzyme, integrase (IN). We constructed a recombinant gene encoding a single-chain, antigen-binding peptide (scAb2-19), which interacted with a carboxyl terminal part of HIV-1 IN. HeLa CD4 cells expressing scAb2-19 localized in either cytoplasmic or nuclear compartment were resistant to HIV-1 infection at an multiplicity of infection (MOI) of 0.25 or 0.063, but the resistance was overcome when MOI was increased to 1. To determine whether this resistance was due to inhibition of the early events, transduction experiments were performed with a replication-incompetent HIV-1 vector carrying bacterial lacZ driven by an internal Tat-independent cytomegalovirus immediate early promoter. Both cytoplasmic and nuclear expressions of scAb2-19 resulted in decrease in the transduction efficiency on HeLa CD4 cells. This implies that an early step of replication--before or during integration--was affected by the scAb2-19. Furthermore, cytoplasmic expression of scAb2-19 did not affect the viral amount released from the cells transfected with HIV-1 infectious clone DNA (pLAI). However, infectivity relative to reverse transcriptase activity was lower for virions released from the 293T cells cotransfected with pLAI and the cytoplasmic scAb2-19 expression plasmid than for those released from the 293T cells transfected with pLAI alone. This implies that scAb2-19 reduced infectivity of released virions by interfering a late step of the viral replication. The single-chain, antigen-binding peptide molecule may prove useful not only for studies of the functions of IN and its role in the viral life cycle but also for developing a gene therapy strategy against AIDS.

Serum testosterone concentrations are frequently in the low-normal range (lowest quartile, <500 ng/dl) in men with AIDS-wasting syndrome (AWS) and in other chronic wasting disorders. The response of patients in this group to androgen treatment has not been determined, however. Eighteen men with AWS (mean +/- standard error [SE]: 87% +/- 1% usual body weight; CD4 count 90 +/- 24) and borderline low serum testosterone concentrations (382 +/- 33 ng/dl) completed a 21-day placebo-controlled inpatient metabolic ward study comparing intramuscular (i.m.) placebo (n = 7) with low-dose (65 mg/week; n = 4) and high-dose (200 mg/week; n = 7) nandrolone decanoate, a testosterone analogue. Nitrogen balance, stable isotope-mass spectrometric measurement of de novo lipogenesis (DNL), resting energy expenditure, and gonadal hormone levels were measured. Both low-dose and high-dose nandrolone resulted in significant nitrogen retention (33-52 g nitrogen/14 days, representing gains of 0.5 to 0.9 kg lean tissue/week) compared with placebo (loss of 11 g nitrogen/week). This was reflected biochemically in a borderline significant reduction of high DNL (p < .06). Serum testosterone and gonadotropins were suppressed whereas resting energy expenditure was unchanged by nandrolone treatment. In 10 study subjects completing a 12-week open-label follow-up phase, body weight increased by 4.9 +/- 1.2 kg, including 3.1 +/- 0.5 kg lean body mass, and treadmill exercise performance also improved. In summary, nandrolone decanoate therapy in the absence of an exercise program in borderline hypogonadal men with AWS caused substantial nitrogen retention compared with placebo, similar in extent to the nitrogen retention previously achieved with recombinant growth hormone. It is reasonable to expand the criteria for androgen treatment in AWS to include at least patients in the lowest quartile of serum testosterone.

Objective: Estimates of HIV prevalence in 1995 among all adults in Zimbabwe range between about 18% and 24%. The objective of this study was to estimate, for Zimbabwe, the impact of HIV infection on adult mortality, by age and gender, between 1995 and the year 2000.

Methods: For this analysis, we used 1992 census data to estimate the number of non-HIV-related deaths, and a short-term projection model to estimate the number of deaths attributed to HIV infection in 1995 and the year 2000.

Results: It was estimated that between 52% and 60% of all adult deaths in 1995 were attributed to HIV infection, and between 69% and 76% in both males and females in the group between 20 and 39 years of age. The estimated adult mortality rate per 1000 increased from 9.8 in 1987 (based on census data) to between 20.6 and 24.3 in 1995. For the year 2000, it was projected that between 66% and 73% of all adult deaths would be attributed to HIV infection, and between 81% and 86% in those aged 20 to 39 years. The estimated adult mortality rate in the year 2000 increased to between 29.1/1000 and 36.6/1000. Even if all transmission was assumed to cease after 1995, it was projected that >60% of adult deaths would be attributed to HIV in the year 2000. Adult population growth is projected to decrease to between 0.3% and 1.0% in the year 2000.

Conclusion: Results suggest that the impact of HIV infection on mortality in Zimbabwe is already severe and will continue to increase. Efforts to reduce numbers of new HIV infections today will serve to reduce the future burden of mortality, particularly in the longer term.