Shedding of human herpesvirus 8 in oral and genital secretions from HIV-1-seropositive and -seronegative Kenyan women

Polymerase chain reaction was used to determine the prevalence and correlates of human herpesvirus 8 (HHV8) in saliva, mouth, cervical, vaginal, plasma, and peripheral-blood mononuclear cell (PBMC) samples from 174 HHV8-seropositive female prostitutes in Mombasa, Kenya. The prevalence of detection of HHV8 was 32% in saliva samples, 28% in mouth swabs, 4% in cervical swabs, 2.3% in vaginal swabs, 9% in plasma samples, and 18% in PBMC samples. Human immunodeficiency virus type 1 (HIV-1) seropositivity was associated with detection of HHV8 from any mucosal surface (odds ratio, 2.1 [95% confidence interval, 1.1-4.0]). In HIV-1-seropositive women, there was no association between detection of HHV8 and either CD4 count or HIV-1 viral load.     

Human immunodeficiency virus in plasma and cervicovaginal secretions in Filipino women

This study examined 30 HIV-infected women in Manila to assess the relationship between cervicovaginal and plasma HIV-1 viral load. An interview and gynaecologic examination was conducted and cervicovaginal lavage (CVL) and venous blood specimens were collected. HIV-1 RNA was detected in plasma samples of 24 patients (80%) and in CVL samples of 18 women (60%); 16 patients (53%) had detectable levels in both. CVL HIV-1 RNA was detectable in 75% of women (6/8) with plasma viral loads between 10,000 and 100,000 copies/mL and in 77% of women (10/13) with plasma viral loads higher than 100,000 copies/mL (P =0.0086). Among women with CD4 cell counts of less than 200, 200-500, and greater than 500/mm(3), CVL HIV-1 RNA was detected in 73%, 69%, and 17% of women, respectively (P =0.1428). HIV-1 RNA shedding in the genital tract was significantly associated with plasma viral load.     

Postnatal human herpesvirus 8 and human immunodeficiency virus type 1 infection in mothers and infants from Zambia

The specific route and timing of human herpesvirus (HHV) 8 infection in regions where Kaposi sarcoma is endemic are not known. HHV-8 infection and any risk factors that may be associated with HHV-8, including human immunodeficiency virus (HIV) type 1 infection, were monitored during the 12-month postdelivery period for 416 mothers and 485 infants from Lusaka, Zambia. HHV-8 incident infection rates during this period were 3.2 and 5.3 infections/100 person-years for infants and mothers, respectively. HHV-8 infection among infants was not associated with HHV-8 or HIV-1 infection in the mother. Among the HHV-8-positive infants, 2 of 12 tested were found to have HHV-8 DNA in their peripheral blood mononuclear cells at birth, which suggests that in utero infection is possible. However, most HHV-8-positive infants appeared to have acquired infection either intrapartum or postpartum. The present study indicates that transmission of HHV-8 to infants can occur early and is likely via multiple routes.     

Interaction of human immunodeficiency virus type 1 and human herpesvirus type 8 infections on the incidence of Kaposi's sarcoma

To determine Kaposi's sarcoma (KS) risk related to timing of human immunodeficiency virus type 1 (HIV-1) and human herpesvirus type 8 (HHV-8) infections, stored longitudinal sera from 400 homosexual men with known dates of HIV-1 seroconversion (+/-4.5 months) were tested for HHV-8 antibody. Times from HHV-8 seroconversion to KS were compared for the 69 men who became infected with HHV-8 after acquiring HIV-1 to the 182 men who were HHV-8 seropositive before their HIV-1 infection. None developed KS before coinfection. HHV-8 seroconversion after HIV-1 infection increased the risk of KS (risk ratio, 2.55; 95% confidence interval, 1.06-6.10) compared with those infected with HHV-8 before HIV-1. The KS hazards in HHV-8-infected men increased by 60% (P<.001) for each year of HIV-1 infection. Faster CD4 cell loss and higher HIV-1 RNA levels significantly predicted KS. The quicker development of KS in men acquiring HHV-8 after HIV-1 and its association with CD4 slope argues that KS is more likely if HHV-8 infection occurs in an immunocompromised person.     

A prospective study of hormonal contraceptive use and cervical shedding of herpes simplex virus in human immunodeficiency virus type 1-seropositive women

Cross-sectional analyses have demonstrated an association between use of hormonal contraceptives and shedding of herpes simplex virus (HSV). This prospective study evaluated the effect of initiating use of hormonal contraception on cervical HSV detection. Two hundred women who were seropositive for HSV-2 and human immunodeficiency virus (HIV) type 1 were examined for cervical mucosal HSV by use of quantitative DNA polymerase chain reaction before and after beginning the use of hormonal contraceptives. Cervical HSV was detected in 32 women (16.0%) before initiating and in 25 women (12.5%) after initiating use of hormonal contraception (P=.4). There were no significant differences in HSV shedding among the subgroups of women starting combination oral contraceptives containing both estrogen and progesterone or progesterone-only contraceptives. Among the 54 women who shed HSV at least once, the median change in cervical HSV after initiation of hormonal contraception was -313 copies/swab. In this prospective study, use of hormonal contraceptives did not increase detection of cervical HSV.     

Antibodies to human immunodeficiency virus type 1 in the urine specimens of HIV-1-seropositive individuals

Specific antibodies to human immunodeficiency virus type 1 (HIV-1) were detected in 200-fold concentrated urine samples, but none were detected in unconcentrated urine specimens, from 100 randomly selected HIV-1--seropositive individuals by enzyme-linked immunosorbent assay (ELISA) and Western blot techniques using the manufacturer's recommended procedures. Using modified methods for both the ELISA and Western blot tests, antibodies to HIV-1 have also been detected in the unconcentrated urine specimens from the same HIV-1--seropositive individuals. No difference in the frequency of antibodies to HIV-1 were found between unconcentrated and 200-fold concentrated urine samples when tested by the modified methods. HIV-1 core antigen (p24) was not detected in either the concentrated or the unconcentrated HIV-1--seropositive adult urine samples; none of these individuals showed overt clinical or laboratory evidence of renal dysfunction. The titer of the antibodies to HIV-1 found in the urine specimens was found to be parallel with the titer of antibodies to HIV-1 in the corresponding individual's serum. Further elucidation of the pathophysiology and the nature of the specific antibodies to HIV-1 observed in the urine of HIV-1--seropositive individuals is under investigation in our laboratories.     

Cellular replication of human immunodeficiency virus type 1 occurs in vaginal secretions

Most human immunodeficiency virus type 1 (HIV-1) transmission worldwide is the result of exposure to infectious virus in genital secretions. However, current vaccine candidates are based on virus isolates from blood. In this study, vaginal secretions from HIV-1-infected women were examined for evidence of cellular viral replication that produced virus with properties different from that in blood. Multiply spliced HIV-1 messenger RNA, which is found only in cells replicating virus, was detected in all vaginal lavage samples tested. There was a strong correlation between the amounts of multiply spliced HIV-1 messenger RNA and of cell-free HIV-1 RNA in the lavage samples. In addition, significant genotypic differences were found in cell-free virus from matched blood plasma and vaginal secretions. Moreover, drug resistance-associated mutations appeared in plasma virus several months before appearing in vaginal virus. These findings indicate that cellular replication of HIV-1 occurs in vaginal secretions and can result in a virus population with important differences from that in blood.     

Prevalence and magnitude of human immunodeficiency virus (HIV) type 1-specific lymphocyte responses in breast milk from HIV-1-seropositive women

Human immunodeficiency virus (HIV) type 1-specific cell-mediated immunity of breast milk may influence the likelihood of mother-to-child transmission of HIV-1 via breast-feeding. In breast-milk specimens collected during the first month postpartum from HIV-1-seropositive women in Nairobi, HIV-1 gag-specific cellular responses were detected in 17 (47%) of 36, and env-specific cellular responses were present in 20 (40%) of 50. Peripheral blood lymphocyte responses against either gag or env were detected in 35 (66%) of the 53 subjects, 18 (51%) of whom had positive gag or env responses in their breast milk. In paired analyses of blood and breast milk, the mean magnitude of responses to env or gag stimulation in breast milk was significantly higher than that in blood and remained higher in breast milk after normalization of responses according to CD8+ lymphocyte count. These results suggest that CD8+ lymphocytes present in breast milk have the capacity to recognize HIV-1-infected cells and may be selectively transported to breast milk to reduce either viral replication or transmission in breast milk.     

Increased risk of early measles in infants of human immunodeficiency virus type 1-seropositive mothers.

An increase in illness due to measles is one of the potential consequences of the human immunodeficiency virus (HIV) epidemic in Africa. During a study of perinatal HIV transmission conducted in Kenya, the risk of acquiring measles before vaccination (9 months of age) was found to be 3.8 times higher in infants born to HIV-seropositive mothers than in control infants (10 [9%] of 109 vs. 5 [3%] of 194 infants; P = .02; odds ratio, 3.8; 95% confidence interval, 1.2-13.2). The majority of infants who developed measles in this study had significant sequelae related to their measles infection. The increased risk of measles appeared to be related to relatively lower anti-measles antibody titers detected in cord blood samples of affected infants born to HIV-seropositive mothers. However, 94% of all infants were susceptible to measles on the basis of ELISA testing at age 6 months regardless of maternal HIV serology. These observations highlight the need for improved measles vaccination strategies in Africa and for studies to delineate the effects of HIV infection on the incidence, presentation, and sequelae of childhood infectious illnesses.     

CD8(+) T cell activation in women coinfected with human immunodeficiency virus type 1 and hepatitis C virus

Immune activation is a hallmark of human immunodeficiency virus type 1 (HIV-1) infection and impacts innate and adaptive immunity. Individuals coinfected with HIV-1 and hepatitis C virus (HCV) may have increased immune activation early in HIV disease because of a high HCV antigen load in tissues such as the liver. We evaluated T cell markers of activation and maturation in women with or without HIV-1 infection, by HCV antibody and HCV RNA status. We found increased percentages of activated CD8(+) T cells (i.e., CD8(+)HLA-DR(+)38(+) cells and CD8(+)CD28(+)HLA-DR(+) cells) but not of CD4(+) T cells among women who tested positive for HIV-1, HCV antibody, and HCV RNA, compared with HIV-1-positive women who tested negative for HCV antibody. Because CD8(+) T cell activation is related to HIV-1 disease progression, these data may have implications for the medical management of patients coinfected with HIV-1 and HCV.     

Polyclonal B-cell activation reveals antibodies against human immunodeficiency virus type 1 (HIV-1) in HIV-1-seronegative individuals.

Identification of human immunodeficiency virus type 1 (HIV-1)-infected individuals is of paramount importance for the control of the spread of AIDS worldwide. Currently, the vast majority of screening centers throughout the world rely on serological techniques. As such, clinically asymptomatic but HIV-infected, seronegative individuals are rarely identified. In this report we show that 18% (30/165) of seronegative individuals who were considered to be a unique cohort of patients at high risk for HIV infection had circulating B cells that, upon in vitro polyclonal activation with pokeweed mitogen, produced antibodies reactive with HIV. Furthermore, polymerase chain reaction analysis of DNA obtained from aliquots of the peripheral blood mononuclear cells from these seronegative but pokeweed mitogen assay-positive individuals tested revealed the presence of HIV-specific sequences in a significant number of samples. In addition, depletion of CD8+ T cells from peripheral blood mononuclear cells of HIV-1-seronegative individuals prior to in vitro culture with pokeweed mitogen resulted in increased sensitivity for detecting HIV-reactive antibodies. This assay has obvious epidemiological implications, especially in the case of high-risk groups, and also provides a simple technique to enhance detection of HIV-infected individuals. Of further interest is the determination of the mechanisms related to the lack of HIV-specific antibodies in the serum of these infected individuals.     

Cutaneous response to recombinant interleukin 2 in human immunodeficiency virus 1-seropositive individuals

We report that 11 human immunodeficiency virus 1 (HIV-1)-seropositive patients, including three AIDS patients, were able to generate a cellular immune response to the intradermal injection of low doses (2-10 micrograms) of recombinant interleukin 2 (rIL-2). A dose-dependent zone of induration appeared at the site of injection, peaked at 24 hr, and was accompanied by the local accumulation of T cells, monocytes, and Langerhans cells. Despite the reductions in the CD4+ T-cell counts in the peripheral blood of most patients, CD4+ T-cells could still be mobilized with rIL-2 injections into the skin. The total number of immigrant cells was equivalent to those in HIV-1-seronegative patients, although the CD4+/CD8+ ratio of the dermal population was reduced. In response to rIL-2, major histocompatibility complex (MHC) class II antigen was expressed on the surface of keratinocytes, Langerhans cells, lymphocytes, and macrophages. In addition, the gamma interferon (IFN-gamma)-induced protein IP-10 rapidly appeared in dermal inflammatory cells and keratinocytes. A majority of HIV-1-seropositive patients demonstrated low or absent responses to common skin-test antigens. Those with positive zones of induration were often defective in the cellular expression of the IFN-gamma-induced MHC class II antigen. The simultaneous administration of rIL-2 and soluble antigen at widely separated cutaneous sites led to an enhancement of skin-test antigen reactivity in seropositive patients. The results suggest that local administration of rIL-2 to seropositive patients may act systemically, stimulating cellular immunity to recall antigens, and thus may be of potential benefit in the defense against opportunistic pathogens encountered in HIV-1 infection.     

Evidence of genetic variability of human immunodeficiency virus type 1 in plasma and cervicovaginal lavage in ethiopian women seeking care for sexually transmitted infections

Most human immunodeficiency virus type 1 (HIV-1) transmission in developing countries occurs through heterosexual intercourse or during birth from mother to child. It is critical to characterize the virus of the genital tract variants as a target for the development of an HIV-1 vaccine and microbicidal therapies. We compared the C2V3 env domain genetic diversity of HIV-1 in female genital secretions and in plasma from Ethiopian women seeking care for sexually transmitted infections (STIs). Sequences within an individual differed between the plasma and cervicovaginal lavage (CLV) compartments with nucleotide and amino acid median difference values of 8.3 and 4.8%, respectively. Sequence diversity in CVL was greater than in plasma. And the V3 loop positive charge was often more elevated in CVL. These are markers of the differential evolution of the viruses in CVL and peripheral blood indicating that limited evolution at the site of contact is not the limiting factor determining the preferential transmission of macrophage tropic viruses.     

Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis.

To determine the contribution of herpes simplex type 2 (HSV-2) infection to the risk of human immunodeficiency virus (HIV) acquisition, a systematic review of literature and data synthesis were done. Thirty-one studies addressed the risk of HIV infection in HSV-2-seropositive persons. For 9 cohort and nested case-control studies that documented HSV-2 infection before HIV acquisition, the risk estimate was 2.1 (95% confidence interval, 1.4-3.2). Thus, the attributable risk percentage of HIV to HSV-2 was 52%, and the population attributable risk percentage was 19% in populations with 22% HSV-2 prevalence but increased to 47% in populations with 80% HSV-2 prevalence. For 22 case-control and cross-sectional studies, the risk estimate was 3.9 (95% confidence interval, 3.1-5.1), but the temporal sequence of the 2 infections cannot be documented. Control strategies for HSV-2 need to be incorporated into control of sexually transmitted infections as a strategy for HIV prevention.     

Molecular analysis of human papillomavirus type 52 isolates detected in the genital tract of human immunodeficiency virus-seropositive and -seronegative women

Human papillomavirus (HPV) type 52 DNA was detected in cervicovaginal lavage samples from 91 (12.4%) of 732 human immunodeficiency virus (HIV)-seropositive women and 23 (7.1%) of 323 HIV-seronegative women (P=.0004). HIV infection was an independent predictor for HPV-52 infection when controlling for age and sexual activity (odds ratio, 2.21; 95% confidence interval, 1.30-3.75: P=.003). We describe the genomic polymorphism of 114 HPV-52 isolates. Long control region (LCR) mutations defined 27 HPV-52 variants. Nearly 32% of HPV-52 isolates carried deletions in the LCR. E6 and E7 mutations defined 17 and 9 variants, respectively. Five nonsynonymous E6 mutations were clustered from amino acids 92 to 94, near the putative p53 binding area. White women were more frequently infected by the prototype strain than were women of African descent (P=.0001). The genetic diversity of HPV-52 should facilitate the investigation of the role of genomic variations in cervical disease.