Gender differences in HIV-1 diversity at time of infection.

To develop an HIV-1 vaccine with global efficacy, it is important to identify and characterize the viruses that are transmitted, particularly to individuals living in areas of high incidence. Several studies have shown that virus from the blood of acutely infected adults was homogeneous, even when the virus population in the index case was genetically diverse. In contrast to those results with mainly male cohorts in America and Europe, in several cases a heterogeneous virus population has been found early in infection in women in Africa. Thus, we more closely compared the diversity of transmitted HIV-1 in men and women who became infected through heterosexual contact. We found that women from Kenya were often infected by multiple virus variants, whereas men from Kenya were not. Moreover, a heterogeneous virus was present in the women before their seroconversion, and in each woman it was derived from a single index case, indicating that diversity was most likely to be the result of transmission of multiple variants. Our data indicate that there are important differences in the transmitted virus populations in women and men, even when cohorts from the same geographic region who are infected with the same subtypes of HIV-1 are compared.

Studies of human immunodeficiency virus type 1 mucosal viral shedding and transmission in Kenya.

If human immunodeficiency virus type 1 (HIV-1) vaccines are to be highly effective, it is essential to understand the virologic factors that contribute to HIV-1 transmission. It is likely that transmission is determined, in part, by the genotype or phenotype (or both) of infectious virus present in the index case, which in turn will influence the quantity of virus that may be exchanged during sexual contact. Transmission may also depend on the fitness of the virus for replication in the exposed individual, which may be influenced by whether a virus encounters a target cell that is susceptible to infection by that specific variant. Of interest, our data suggest that the complexity of the virus that is transmitted may be different in female and male sexual exposures.

Changes in the extracellular envelope glycoprotein of variants that evolve during the course of simian immunodeficiency virus SIVMne infection affect neutralizing antibody recognition, syncytium formation, and macrophage tropism but not replication, cytopathicity, or CCR-5 coreceptor recognition.

Simian immunodeficiency virus SIVMne, like human immunodeficiency virus, evolves from a macrophage-tropic, non-syncytium-inducing virus at early times in infection to a T-cell-tropic, syncytium-inducing, cytopathic virus population over the course of progression to AIDS. Because the viruses isolated late in SIVMne infection of macaques include a complex mixture of variants, the viral determinants of such phenotypic changes have not been defined. To identify genetic changes that are important to virus evolution in the host, we constructed chimeric viruses by introducing variant envelope genes representative of proviruses throughout the course of infection and disease into the SIVMne parental clone (SIVMneCL8) that infected the macaque. The chimeric viruses expressed sequences encoding the surface unit of the envelope glycoprotein (Env-SU) of variants cloned between 35 and 170 weeks postinfection. The chimera with Env-SU from 35 weeks postinfection encoded only four changes in V1 compared to SIVMneCL8, whereas the chimeras encoding Env-SU from variants isolated later in infection encoded progressively more mutations both in V1 and elsewhere. Like SIVMneCL8, the chimeras were infectious for CEMx174 cells and macaque peripheral blood mononuclear cells. However, in contrast to SIVMneCL8, the chimeric viruses did not infect macaque macrophages, although each retained the ability to recognize the CCR-5 coreceptor. Thus, these data provide direct evidence that changes which evolve in Env-SU during the course of SIVMne infection do not alter CCR-5 interactions. Viruses encoding Env-SU from the latest times in infection (121 to 170 weeks postinfection), after disease was apparent, were syncytium inducing. However, these viruses were not highly cytopathic, suggesting that additional viral determinants may be required for the rapidly replicating, cytopathic phenotype of the uncloned mixed variant population. Changes in Env-SU did allow the virus to escape serum neutralizing antibodies that recognized the SIVMneCL8 parent. Moreover, the chimera encoding the Env-SU of a virus from 35 weeks postinfection, which differed from SIVMneCL8 only in V1, was not sensitive to neutralization by infected macaque sera, suggesting that V1 may define a portion of the principal neutralizing determinant for SIVMne. Together, these data suggest that SIV variants with changes in the Env-SU may be selected primarily by virtue of their ability to escape neutralizing antibody recognition.

Four-week supplementation with a natural dietary compound produces favorable changes in body composition.

The purpose of this study was to determine whether a natural dietary supplement produced favorable changes in body composition during a 4-week diet- and-exercise program. The active compound contains a patented combination of chromium picolinate, inulin, capsicum, L-phenylalanine, and other lipotropic nutrients. A double-blind, weight-loss intervention design was used. Participants were randomly assigned to either a diet/exercise/supplement group (n = 56) or a diet/exercise/placebo group (n = 67). Caloric intake was reduced to 1500 kcal/d and participants walked for 45 minutes, 5 days a week, to attain between 60% and 80% of predicted maximal heart rate. Analysis of covariance (ANCOVA) showed significant differences (P < .05) between groups in percent body fat, fat mass, and fat-free mass; no significant differences were found (P > .05) in body weight, body mass index, or energy intake. Independent t tests showed no significant differences (P > .05) in diet composition between groups. Results indicate that the addition of a natural dietary supplement during a 4-week diet-and-exercise weight-loss program accelerates the rate of body fat loss and helps maintain fat-free mass (lean tissue), thereby producing favorable changes in body composition.

Human immunodeficiency virus type 1 coreceptors participate in postentry stages in the virus replication cycle and function in simian immunodeficiency virus infection.

Primate lentiviruses use chemokine coreceptors in addition to the CD4 receptor to initiate virus infection. Simian immunodeficiency virus (SIV) productively infects human cells expressing CD4 and the human allele of the chemokine coreceptor CCR-5 as efficiently as it infects macaque cells expressing human CD4, suggesting that SIV can function with either a simian or a human coreceptor in conjunction with human CD4. In the same macaque cells expressing human CD4, the replication of human immunodeficiency virus type 1 (HIV-1) is blocked at several stages of infection; some isolates are restricted prior to reverse transcription, while others, including some macrophage-tropic and primary isolates, are restricted at a step after reverse transcription but prior to migration of the preintegration complex to the nucleus. Both blocks in HIV-1 replication can be relieved by either expression of the appropriate human coreceptor (CCR-5 or CXCR-4) or expression of SIV gene products in cis with the HIV-1 envelope as a chimera between SIV and HIV-1 (SHIV). Thus, a virus with a SIV core and HIV-1 envelope can efficiently infect macaque cells expressing human CD4, presumably by interacting with the simian coreceptor, whereas a virus with an HIV-1 core and an HIV-1 envelope requires expression of the human allele of the coreceptor for productive infection of these cells. These studies suggest that there are interactions among the coreceptor, the viral envelope, and another viral gene product that govern postentry steps of virus replication. These data are consistent with the hypothesis that such interactions may be required for translocation of the virus core to the nucleus. Moreover, the differential abilities of SIV and HIV-1 to function in these processes with heterologous primate coreceptors may have implications for cross-species transmission.

Outcome of fetal meningomyelocele after vaginal delivery.

Eight neonates with meningomyelocele were delivered vaginally. Diagnosis of meningomyelocele was made by ultrasonography during the latter half of pregnancy in three patients. The remaining five did not have ultrasound examination during the antenatal period. None of the meningomyelocele sacs (less than or equal to 4 cm in diameter) was ruptured at the time of delivery. Cesarean section may not be necessary for all fetuses with meningomyelocele.

Ectopic pregnancy. An eight-year review.

Ruptured ectopic pregnancy constitutes a major gynecologic emergency that may result in death. From January 1968 through December 1975, 313 patients with ectopic pregnancy were treated at Chicago Lying-In Hospital. The historical and physical findings, diagnostic procedures, causative factors and patient management are reviewed and discussed. The most common symptoms were abdominal pain and amenorrhea. More than half the patients were misdiagnosed prior to admission. Only 30% had distinct adnexal masses. The treatment of choice was salpingectomy unless the opposite tube was absent or damaged. Three deaths occurred in this series. Only 31% of the patients gave histopathologic evidence of pelvic inflammatory disease.

PIP: 313 patients with ectopic pregnancy were treated at Chicago Lying-In Hospital in 1968-1975, for a frequency of 1 in 72 deliveries. Historical and physical findings, diagnostic procedures, causative factors, and patient management were reviewed for 284 of these patients. 97.5% of the pregnancies were tubal. 25% of the patients were nulliparas and 31.7% were primiparas. 34.9% had had 1 or more previous abortions. The mean age of the patients was 28. Most had been using no contraception, and only 3.9% had an IUD in situ. The most common symptoms were abdominal pain (96.7%) and amenorrhea (73.6%), while the most frequent abdominal findings were tenderness (83.4%), rebound pain (41.2%), and guarding (28.9%). Adnexal tenderness was found in 72.2% and 30% had distinct adnexal masses. An initial misdiagnosis of pelvic inflammatory disease was made in 132 (46.5%) cases. A culdocentesis and slide latex agglutination inhibition pregnancy test performed in 167 and 102 patients, respectively, gave 82.6 and 73.5% positive rates. Diagnostic laparoscopy was used routinely after 1970 on all nonacute patients in whom ectopic pregnancy was suspected, and this led to a significant drop in the rate of ruptured pregnancies (63% pre-1970 and 45% post-1970). 25% of patients were sterilized, but the treatment of choice was salpingectomy unless the opposite tube was absent or damaged. Gross evidence of pelvic inflammatory disease was noted in 36% of patients and 31% had salpingitis. The most common postoperative complication was fever (42.2%). 3 deaths occurred in the series (2 due to acute pulmonary edema resulting from fluid overload), for a maternal death rate from ectopic gestation of 13.83/100,000 live births. No fetuses survived.