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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many people who remain persistently seronegative despite frequent HIV exposure have HIV-specific immune responses. The study of these may provide information about mechanisms of natural protective immunity to HIV-1. We describe the specificity of cytotoxic T lymphocyte responses to HIV in seronegative prostitutes in Nairobi who are apparently resistant to HIV infection. These women have had frequent exposure to a range of African HIV-1 variants, primarily clades A, C, and D, for up to 12 yr without becoming infected. Nearly half of them have CTL directed towards epitopes previously defined for B clade virus, which are largely conserved in the A and D clade sequences. Stronger responses are frequently elicited using the A or D clade version of an epitope to stimulate CTL, suggesting that they were originally primed by exposure to these virus strains. CTL responses have been defined to novel epitopes presented by HLA class I molecules associated with resistance to infection in the cohort, HLA-A*6802 and HLA-B18. Estimates using a modified interferon-gamma Elispot assay indicate a circulating frequency of CTL to individual epitopes of between 1:3,200 and 1:50,000. Thus, HIV-specific immune responses-particularly cross-clade CTL activity- may be responsible for protection against persistent HIV infection in these African women.
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PMID:Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi. 980 77

A prospective study involving the management of forty six patients with Fournier's gangrene was carried out at the Kenyatta National Hospital, Nairobi over a period of two years. The age range was nine to 81 years with a mean of 40.27 years indicating that the lesion is common and affects all age groups in this locality. The majority of patients (60.86%) presented with advanced lesions involving scrotal ulcers (45.65%) and gangrene (15.22%). Results of bacterial culture from scrotal wound swabs isolated multiple organisms in 8.15% of the patients, a point which should be taken into consideration during antibiotic selection. Forty one patients (89.13%) had surgical procedures in addition to antibiotics and other supportive measures. Five other patients (10.87%) who presented with early lesions had medical treatment only with antibiotics, antipyretics and analgesics. The average duration of hospitalisation was sixteen days. Two patients (4.35%) one of whom was HIV positive died from septicaemia during the study period. Recurrent scrotal infection occurred in two patients (4.35%) after discharge from the hospital and were treated satisfactorily at the surgical outpatient clinic.
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PMID:Management of Fournier's gangrene at the Kenyatta National Hospital, Nairobi. 980 23

A small group of women (n = 80) within the Nairobi-based Pumwani Sex Workers Cohort demonstrates epidemiologic resistance to HIV-1 infection. Chemokine receptor polymorphisms and beta-chemokine overproduction have been among the mechanisms suggested to be responsible for resistance to HIV-1 infection. This study attempts to determine if any of those mechanisms are protecting the HIV-1-resistant women. Genetic analysis of CCR5 and CCR3 from the resistant women demonstrated no polymorphisms associated with resistance. Expression levels of CCR5 among the resistant women were shown to be equivalent to that found in low-risk seronegative (negative) controls, while CXCR4 expression was greater among some of the resistant women. In vitro infection experiments showed that phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from resistant women were as susceptible to infection to T cell- and macrophage-tropic North American and Kenyan HIV-1 isolates as were the PBMCs from negative controls. No significant difference in circulating plasma levels of MIP-1alpha and MIP-1beta were found between the resistant women and negative or HIV-1-infected controls. In vitro cultures of media and PHA-stimulated PBMCs indicated that the resistant women produced significantly less MIP-1alpha and MIP-1beta than did negative controls and no significant difference in RANTES levels were observed. In contrast to studies in Caucasian cohorts, these data indicate that CCR5 polymorphisms, altered CCR5 and CXCR4 expression levels, cellular resistance to in vitro HIV-1 infection, and increased levels of beta-chemokine production do not account for the resistance to HIV-1 infection observed among the women of the Pumwani Sex Workers Cohort.
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PMID:HIV type 1 resistance in Kenyan sex workers is not associated with altered cellular susceptibility to HIV type 1 infection or enhanced beta-chemokine production. 984 Feb 85

In sub-Saharan Africa, where the effects of human immunodeficiency virus type 1 (HIV-1) have been most devastating, there are multiple subtypes of this virus. The distribution of different subtypes within African populations is generally not linked to particular risk behaviors. Thus, Africa is an ideal setting in which to examine the diversity and mixing of viruses from different subtypes on a population basis. In this setting, it is also possible to address whether infection with a particular subtype is associated with differences in disease stage. To address these questions, we analyzed the HIV-1 subtype, plasma viral loads, and CD4 lymphocyte levels in 320 women from Nairobi, Kenya. Subtype was determined by a combination of heteroduplex mobility assays and sequence analyses of envelope genes, using geographically diverse subtype reference sequences as well as envelope sequences of known subtype from Kenya. The distribution of subtypes in this population was as follows: subtype A, 225 (70.3%); subtype D, 65 (20.5%); subtype C, 22 (6.9%); and subtype G, 1 (0.3%). Intersubtype recombinant envelope genes were detected in 2.2% of the sequences analyzed. Given that the sequences analyzed represented only a small fraction of the proviral genome, this suggests that intersubtype recombinant viral genomes may be very common in Kenya and in other parts of Africa where there are multiple subtypes. The plasma viral RNA levels were highest in women infected with subtype C virus, and women infected with subtype C virus had significantly lower CD4 lymphocyte levels than women infected with the other subtypes. Together, these data suggest that women in Kenya who are infected with subtype C viruses are at more advanced stages of immunosuppression than women infected with subtype A or D. There are at least two models to explain the data from this cross-sectional study; one is that infection with subtype C is associated with a more rapid disease progression, and the second is that subtype C represents an older epidemic in Kenya. Discriminating between these possibilities in a longitudinal study will be important for increasing our understanding of the role of specific subtypes in the transmission and pathogenesis of HIV-1.
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PMID:Subtypes of human immunodeficiency virus type 1 and disease stage among women in Nairobi, Kenya. 1019 37

HIV-specific cytotoxic T-lymphocytes (CTL) are believed to play a key part in the control of virus levels throughout HIV infection. An important goal of a potential prophylactic vaccine against HIV is therefore to elicit a strong CTL response which is broadly cross-reactive against a diverse range of HIV strains. We have detected HIV-specific CTL in two groups of highly-exposed but persistently seronegative female sex workers in Africa which show extensive cross-reactivity between different viral sequences. In a small group of women exposed to both HIV-1 and HIV-2 in Gambia, studied over 4 years, we have repeatedly detected HLA-B35-restricted CTL which exhibit cross-reactivity between the HIV-1 and HIV-2 sequences of the CTL epitopes. In women with particularly intense exposure to what are likely to be multiple clades of HIV-1 in Nairobi Kenya, we have detected CTL directed towards epitopes conserved between HIV-1 clades. In neither group is there any evidence that variation in CCR5 sequence or expression is responsible for their apparent resistance to HIV infection. However, in seropositive donors from Oxford infected with African strains of HIV-1, we have defined CTL responses which are specific for particular clades and have mapped some unique A clade CTL epitopes, together with others to highly-conserved regions of the virus. Further information about the extent of cross-reactive CTL immunity will be important for future vaccine design and evaluation.
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PMID:Broadly cross-reactive HIV-specific cytotoxic T-lymphocytes in highly-exposed persistently seronegative donors. 1020 28

This study aimed to evaluate the effectiveness of using risk assessment algorithms in predicting sexually transmitted disease (STD) and subsequent IUD-related complications among IUD candidates. The study population was selected among women who desired an IUD insertion in Nairobi, Kenya. The following algorithms drawn from the study of IUD use and HIV infection among these 615 IUD users were evaluated: 1) an STD algorithm based on US Agency for International Development (USAID) Technical Working Group guidelines; 2) a Centers for Disease Control and Prevention (CDC) algorithm for management of chlamydia; 3) a data-derived algorithm modeled from data. Algorithms were also evaluated for prediction of chlamydial and gonococcal infection at 1 month and complications (pelvic inflammatory disease, IUD removals, and IUD expulsions) at 4 months. Results showed that women with STDs were more likely to develop complications than women without STDs (19% vs. 6% risk ratio = 2.9; 95% CI, 1.3-6.5). In STD prediction, the USAID algorithm was 91% sensitive and 56% specific, with LR+ = 2.0 and LR- = 0.2. Category-specific LR for this algorithm identified women with very low (1%) and very high (29%) infection probabilities. Thus, sexually transmitted disease was associated with increased risk for complications after IUD insertion. Moreover, it may be concluded that simple risk assessment criteria can assist in the identification of women at high and low risk for STD among women presenting for IUD insertion; it may also be concluded that the use of simple risk assessment tools may facilitate the identification of women who require close observation, thus reducing the incidence of IUD-related complications.
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PMID:Use of sexually transmitted disease risk assessment algorithms for selection of intrauterine device candidates. 1036 24

This cross sectional study presents a risk scoring system that would identify women at highest risk for sexually transmitted infections (STIs). 1058 randomly selected women participated in the study in Nairobi, Kenya; of these, 1048 participants were included in the analysis. The study was conducted from May 1994 to July 1995 at a clinic sponsored by the Family Planning Association of Kenya. Information pertaining to the demographic, behavioral and social characteristics of the participants was gathered. In addition, a clinical algorithm, which includes physical examination, microscopy, and leukocyte esterase (LE) urine dipsticks, was employed to detect gonorrhea and chlamydia infections among asymptomatic women. The results revealed that the prevalence of STIs, including HIV-1, was high among women attending this urban family planning clinic. Standard demographic, behavioral, and clinical characteristics were only weakly associated with infection, resulting in poor sensitivity and specificity calculations in the risk scores. Detection of cervical infections gave a sensitivity of 85% and a specificity of 30%. A positive LE urine dipstick had a sensitivity of 63% and a specificity of 47%. Although the addition of physical examination and LE dipstick to the work-up improved the sensitivity of case detection, it did not improve the overall validity of the scoring system.
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PMID:Predicting Neisseria gonorrhoeae and Chlamydia trachomatis infection using risk scores, physical examination, microscopy, and leukocyte esterase urine dipsticks among asymptomatic women attending a family planning clinic in Kenya. 1049 40

The population structure of Streptococcus pneumoniae in a sample of 134 carried antibiotic-susceptible isolates, and 53 resistant and susceptible invasive isolates, was examined using a DNA-based version of multilocus enzyme electrophoresis: multilocus restriction typing (MLRT). This involved RFLP analysis of PCR products generated from nine loci of housekeeping genes located around the pneumococcal chromosome. The combination of alleles at each of the nine loci gave an allelic profile or restriction type (RT). All carried (throat or nasopharyngeal) isolates from children or adults in Oxford and Manchester, UK, and from an HIV-seropositive cohort in Nairobi, Kenya, showed an epidemic population structure. Twelve carried clonal groups, each with different serotypes, were identified at both locations within the UK. Almost all of the carried clones examined (16/17) were found to possess identical RTs or sequence types (STs) to invasive isolates, indicating that frequently carried clones are also associated with cases of invasive disease. As expected from previous studies, the population of 53 invasive, mainly penicillin-resistant, isolates was also found to be at linkage equilibrium. Serotype switching was identified among 14% of RTs that possessed two or more members, or 5.7% of individual isolates within these RTs. In support of a population structure in which there is frequent recombination, there is also clear evidence that the trpA/B locus within pneumococci has evolved by horizontal gene transfer. A non-serotypable isolate from an HIV-seropositive patient in Kenya was clearly genetically distinct from other strains studied, with unique alleles at eight out of nine loci examined. However, it was initially identified as a pneumococcus by a 16S RNA gene probe (Gen-Probe), optochin susceptibility and the presence of pneumolysin and autolysin.
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PMID:Population biology of Streptococcus pneumoniae isolated from oropharyngeal carriage and invasive disease. 1058 38

Understanding how individuals with a high degree of HIV exposure avoid persistent infection is paramount to HIV vaccine design. Evidence suggests that mucosal immunity, particularly virus-specific CTL, could be critically important in protection against sexually acquired HIV infection. Therefore, we have looked for the presence of HIV-specific CD8+ T cells in cervical mononuclear cells from a subgroup of highly HIV-exposed but persistently seronegative female sex workers in Nairobi. An enzyme-linked immunospot assay was used to measure IFN-gamma release in response to known class I HLA-restricted CTL epitope peptides using effector cells from the blood and cervix of HIV-1-resistant and -infected sex workers and from lower-risk uninfected controls. Eleven of 16 resistant sex workers had HIV-specific CD8+ T cells in the cervix, and a similar number had detectable responses in blood. Where both blood and cervical responses were detected in the same individual, the specificity of the responses was similar. Neither cervical nor blood responses were detected in lower-risk control donors. HIV-specific CD8+ T cell frequencies in the cervix of HIV-resistant sex workers were slightly higher than in blood, while in HIV-infected donor cervical response frequencies were markedly lower than blood, so that there was relative enrichment of cervical responses in HIV-resistant compared with HIV-infected donors. HIV-specific CD8+ T cell responses in the absence of detectable HIV infection in the genital mucosa of HIV-1-resistant sex workers may be playing an important part in protective immunity against heterosexual HIV-1 transmission.
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PMID:HIV-1-specific mucosal CD8+ lymphocyte responses in the cervix of HIV-1-resistant prostitutes in Nairobi. 1064 Jul 81

Certain human leukocyte antigens, by presenting conserved immunogenic epitopes for T cell recognition, may, in part, account for the observed differences in human immunodeficiency virus type 1 (HIV-1) susceptibility. To determine whether HLA polymorphism influences HIV-1 susceptibility, a longitudinal cohort of highly HIV-1-exposed female sex workers based in Nairobi, Kenya, was prospectively analyzed. Decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related HLA alleles (A2/6802 supertype; incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.27-0.72; P=.0003). The alleles in this supertype are known in some cases to present the same peptide epitopes for T cell recognition. In addition, resistance to HIV-1 infection was independently associated with HLA DRB1*01 (IRR, 0.22; 95% CI, 0.06-0.60; P=.0003), which suggests that anti-HIV-1 class II restricted CD4 effector mechanisms may play an important role in protecting against viral challenge. These data provide further evidence that resistance to HIV-1 infection in this cohort of sex workers is immunologically mediated.
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PMID:Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection. 1082 57


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