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Biomedical subjects

P Kanki

Publications and source records attributed to P Kanki.

At least 19 recordsLinked to original sources

Rapid HIV testing and counselling in labour in a northern Nigerian setting.

Between April and August 2004, all pregnant women in labour at JUTH, were offered rapid HIV testing and counselling with opportunity to decline testing. HIV positive women were offered the standard nevirapine mono-therapy prophylaxis regimen (HIVNET 012). Four hundred and thirty (99.8%) of the 431 pregnant women who were offered rapid HIV testing and counselling, agreed to test. A sero-conversion rate of 2.1% (5 of 235) was found among women who had previously tested negative for HIV during the index pregnancy. A seroprevalence rate of 9.6% (16 of 166) was found among women with unknown HIV status. One patient who had an indeterminate HIV status prior to labour tested positive in labour. Rapid HIV testing and counselling in labour is a useful practice in high prevalence settings since it detects a substantial number of HIV-infected women and HIV-exposed babies that would otherwise have missed interventions to prevent MTCT.

Adolescent↗

HIV infection among pregnant women in Nigeria.

OBJECTIVES: To determine risk factors for HIV among pregnant women (N = 2657) receiving antenatal services in Jos, Plateau state, Nigeria. METHODS: Information about potential risk factors was obtained at interview. Biological samples were collected for detection of HIV and other sexually transmitted infections (STIs). RESULTS: The prevalence of HIV was 8.2%. Women aged 20-29 years had more than 4-fold increased risk of HIV. Women of Catholic (adjusted odds ratio (AOR) = 1.72, 95% CI = 1.01-2.95) and Pentecostal (AOR = 2.57, 95% CI = 1.46-4.52) denominations were more likely to be HIV-infected when compared to Moslem women. The risk of HIV was also increased among women with multiple marriages and in women married to a banker/accountant. Other predictors of HIV were having a husband with other partners, perceived risk of HIV, STIs, candidiasis and bacterial vaginosis. CONCLUSIONS: Development of effective interventions, including behavioral change, expansion of perinatal HIV prevention services and STI control, should be given the highest priority.

Adult↗

CCR5 receptor expression is down-regulated in HIV type 2 infection: implication for viral control and protection.

HIV-2 is known to display an attenuated phenotype in vivo with prolonged time to disease and decreased rate of transmission. Observational studies in Senegal have demonstrated protection from HIV-1 infection, although the putative mechanism for immunoprotection remains undefined. We evaluated HIV-2-seropositive women from a cohort of commercial sex workers in Dakar, Senegal and identified individuals with very low surface CCR5 receptor expression on CD4+ T cells. In vitro up-regulation of the CCR5 receptor was readily achieved. Down-regulation of the CCR5 was not correlated with activation markers (HLA-DR), beta-chemokine levels, or plasma viral loads. A correlation was observed with HIV-2-specific CD8+ T cell activity as measured by intracellular cytokine production. We postulate that down-regulation of the CCR5 receptor in HIV-2 infection contributes to slower disease course and to the protective mechanism against HIV-1 superinfection, mediated in part by HIV-2-specific cellular immune responses.

CD4-Positive T-Lymphocytes↗

Immunologic and virologic response after tetanus toxoid booster among HIV-1- and HIV-2-infected Senegalese individuals.

Twelve HIV-1-infected, nine HIV-2-infected patients and eight HIV-negative subjects were given a 40IU booster dose of tetanus toxoid (TT). Blood was collected on days 0, 7 and 30 after immunization. Changes in HIV-1 or HIV-2 RNA load were evaluated by nested PCR. TT-IgG antibody levels were quantified by ELISA. CD4 cell counts as well as activation, memory and maturation markers of T lymphocyte subsets were determined by flow cytometry. The induction of apoptosis was investigated using 7-aminoactinomycin D (AAD) and propidium iodide (PI) staining. Proliferative responses to TT and pokeweed mitogen (PWM) were determined by the level of [(3)H] thymidine incorporation. Seven and 30 days after immunization, there was no detectable increase in HIV-1 or HIV-2 plasma load. There were also no changes in CD4 cell counts, CD69, HLA-DR and memory CD45RO or naive CD45RA antigens. Immunization did not increase the spontaneous apoptosis of peripheral blood mononuclear cells (PBMCs), CD4+ and CD8+ T cells subsets neither in controls nor in HIV-infected patients. Similarly, apoptosis induced in vitro by PWM or by the specific TT recall antigen did not vary during the study period. The proliferative response to PWM and to the TT recall antigen was decreased both in HIV-1- and HIV-2-infected patients compared to HIV-negative controls. Immunization significantly increased the TT-IgG levels in healthy controls and in HIV-infected patients. However, the anti-TT-IgG response, as measured by the fold-increase index between days 0 and 30, was significantly higher in healthy controls than in HIV-1- (P=0.036) and HIV-2-infected patients (P=0.003). In conclusion, we found no deleterious immunologic or virologic effect was detected in healthy HIV-1- and HIV-2-infected individuals after antigenic challenge with a TT booster. However, the response to TT vaccination was lower in HIV-1- and in HIV-2-infected individuals than in healthy HIV-negative controls.

Adult↗

Cellular immunity to human immunodeficiency virus type 1 (HIV-1) clades: relevance to HIV-1 vaccine trials in Uganda.

The first prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine trial in Africa, with a clade B immunogen, is currently under way in Uganda, in a region where clades A and D are endemic. The use of a B clade vaccine is based on anticipated cross-recognition of endemic strains of HIV-1 in Uganda, but, in fact, little is known about the cytotoxic T lymphocyte (CTL) responses in that region. Seventeen HIV-1-infected volunteers from Kampala, Uganda, were studied to determine the immune responses elicited by natural infection with local HIV-1 strains. Despite the presence of broad cross-clade recognition, the CTL responses to the infecting viral clade were highest in most people. Recognition of nonendemic clade B antigens was similar to that of the coendemic local clade, and, in some instances, cross-recognition of clade B was greater. Nevertheless, the degree of cross-clade cellular responses we observed lends justification to the use of clade B-based immunogens in the current phase 1 vaccine trial in Uganda.

AIDS Vaccines↗

Resistance to human immunodeficiency virus type 1 in vitro as a surrogate of vaccine-induced protective immunity.

An in vitro assay developed as a correlate of vaccine-induced protection from human immunodeficiency virus (HIV) was validated in populations with relative resistance to HIV-1 as well as in HIV vaccine recipients. Cultures of peripheral blood mononuclear cells (PBMC) were challenged with 10 TCID50 of HIV-1MN or HIV-1BaL, titered in PBMC from normal controls (n=57). PBMC from HIV-1-infected persons with low viremia (n=17), exposed uninfected persons (n=23), and HIV-2-infected Senegalese prostitutes (n=9) were significantly resistant to HIV-1BaL and/or HIV-1MN (P<.001). Among 34 HIV vaccine recipients of live canarypox vector expressing multiple HIV-1 gene products with or without rgp120 booster, PBMC from postvaccination samples were significantly resistant to both strains (P<.001), and cytotoxic T lymphocyte precursor-positive samples were significantly more resistant than were precursor-negative samples (P<.03). This is the first evidence of the induction by vaccination of a validated correlate of protection. This assay should serve as a useful criterion for assessing experimental HIV vaccines before phase III efficacy trials.

AIDS Vaccines↗

HIV prevention among male clients of female sex workers in Kaolack, Senegal: results of a peer education program.

This article reports the results of a peer-led HIV prevention education and condom promotion program among transport workers in Kaolack, Senegal. As part of a 2-year longitudinal follow-up study, changes in men's AIDS-related knowledge, sexual behavior, condom use, and perceived barriers to condom use were evaluated by self-reports obtained from a systematic sample of transport workers interviewed before and after intervention. In addition to men's self-reports, preintervention and postintervention data on men's sexual and condom use behavior were gathered from a sample of licensed, commercial sex workers, who cited transport workers as their primary source of clients. Significant increases in men's HIV-related knowledge, previous use of condoms (from 30.4% to 53.5%), and consistent condom use with regular sex partners were documented over the study period, as were significant declines in perceived barriers to condom use. Though men reported significantly fewer sexual encounters with casual and commercial partners at follow-up compared to baseline, these data were unreliable. Women's postintervention reports indicate that a greater proportion of clients (including, but not limited to transport workers) "always" agree to use condoms (p < .01) compared with baseline and that fewer men offer more money for unprotected sex (p < .01). However, women also report taking greater initiative in the mechanics of condom use (supplying the condom, putting it on, and taking it off) than they did prior to the intervention, and significantly (p < .05) fewer women think that most of their clients know how to use a condom. The findings indicate that the peer-mediated intervention had a positive impact on several important outcomes measured and suggest that HIV prevention efforts need to focus on male client groups despite the logistical and methodological challenges.

Adult↗

V3 serotyping of HIV-1 infection: correlation with genotyping and limitations.

HIV-1 V3 serotyping is a classification of immunodeficiency viruses based on antibody binding to V3 peptides that allows obtaining information on circulating subtypes that could be important for population-based epidemiologic studies. Recently, several laboratories have developed V3 enzyme-immunoassays (EIAs) using V3 peptides of subtypes A to E. In the present study, the utility of including additional peptides of subtypes F to H to the EIA was evaluated on a panel of 203 well-characterized serum samples from patients with diverse geographic origins (22 countries) and known HIV-1 genotype (79 A, 61 B, 21 C, 7 D, 7 E, 21 F, 6 G, 1 H). The results indicate a high predictive value (ppv) for serotypes B (> or =0.86), D (1) and E (0.88), and confirm the difficulty of predicting genotype A or C based on serotype A or C. Results also indicate that inclusion of the F peptide in the V3 EIAs may be useful (ppv = 0.61), but introduction of peptides G and H failed to demonstrate significant sensitivity or specificity for these subtypes. Correlation between serotyping and amino-acid sequences of the V3 region from 103 samples allowed the identification of key amino-acids that appear essential for subtype-specific seroreactivity.

Amino Acid Sequence↗

Cytotoxic T-lymphocyte cross-reactivity among different human immunodeficiency virus type 1 clades: implications for vaccine development.

Despite recent advances in antiviral therapy for human immunodeficiency virus (HIV) infection, successful global intervention will require an effective vaccine. Expanding evidence suggests that cytotoxic T-lymphocyte (CTL) responses will be an important component of such a vaccine. The varying geographic distribution of HIV type 1 (HIV-1) clades, with the relative absence of clade B HIV-1 outside the developed world, is considered a major obstacle to the development of a single efficacious vaccine. An understanding of cross-reactive CTL responses between different HIV-1 clades is crucial in the design of a vaccine which will be broadly immunogenic. In this study, we examined the ability of HIV-1 Gag-, reverse transcriptase-, and Env-specific CTL clones isolated from individuals infected in the United States to recognize non-B clade viral sequences and found that all were cross-reactive with the majority of non-B clade viral sequences tested. We next studied HIV-1-specific CTL responses in African individuals infected with clade A, C, or G virus and evaluated cross-recognition of clade B virus. Of 14 persons evaluated, all demonstrated cross-reactivity with the U.S. clade B viral constructs. We conclude that significant CTL cross-reactivity exists between clade B and non-B epitopes, suggesting that CTL cross-recognition among HIV-1 clades is more widespread than anticipated and that a vaccine based on a single clade may be broadly applicable.

Amino Acid Sequence↗

Sexually transmitted diseases and risk of HIV infection in men attending a sexually transmitted diseases clinic in Dakar, Senegal.

This cross-sectional study was carried out among male outpatients with symptoms of STDs at the STD reference centre at the Institute of Social Hygiene (IHS), Dakar, Senegal, from March 1989 through May 1991. This study was used to determine the prevalence of STDs and HIV among male patients attending an STD clinic and to identify their socio-demographic characteristics and risk factors. A total of 975 patients were enrolled in the study. The most common syndromes were urethritis (76%) and genital ulcers (22%). Considering single infections, the major STD agents were Neisseria gonorrheae (N.gonorrheae, 30%), Chlamydia trachomatis (C.trachomatis, 15%), Treponema pallidum (T.pallidum, 12%), and Haemophilus ducreyi (H.ducreyi, 7%). HIV prevalence was 2.6 percent (25/975). After multivariate analysis, the risk factors associated with HIV infection were a history of sex with prostitutes (odds ratio [OR] = 8.6, 95% confidence interval [CI] = 2.0-37.8), unprotected sexual contact (OR = 5.6, 95% CI = 1.2-25.0), a history of urethritis (OR = 3.4, 95% CI = 1.3-8.9), current STDs due to H.ducreyi or T.pallidum (OR = 6.1, 95% CI = 2-18.8), and mixed STD infection (OR = 5.3, 95% CI = 1.3-21.8). HIV prevalence was quite low in this population compared to similar studies of STD patients from other sub-Saharan African countries. Neisseria gonorrheae and Chlamydia trachomatis were the leading causes of STDs. A history of risky sexual behaviour, previous STDs, current genital ulcers, and mixed STD infections were associated with HIV infection. Further studies are necessary to determine changes in the relationship of STDs and HIV infection in this population.

Adult↗

Reduced rate of disease development after HIV-2 infection as compared to HIV-1.

Human immunodeficiency virus type-2 (HIV-2) is a close relative of the prototype acquired immunodeficiency syndrome (AIDS) virus, HIV-1. HIV-2 is biologically similar to HIV-1, but information is lacking concerning clinical outcomes of HIV-2-infected individuals. From 1985 to 1993, a prospective clinical study was conducted in women with HIV-2 and HIV-1 infection to determine and compare rates of disease development. HIV-1-infected women had a 67% probability of AIDS-free survival 5 years after seroconversion in contrast with 100% for HIV-2-infected women. In addition to having significantly less HIV-related disease outcome in HIV-2 enrollees compared to HIV-1 enrollees, the rate of developing abnormal CD4+ lymphocyte counts with HIV-2 infection was also significantly reduced. This natural history study demonstrates that HIV-2 has a reduced virulence compared to HIV-1.

Acquired Immunodeficiency Syndrome↗

Comparison of transmission rates of HIV-1 and HIV-2 in a cohort of prostitutes in Senegal.

To explore the biological similarities and differences between the HIV-1 and HIV-2 viruses, we model the probability of male-to-female transmission of either HIV virus as a function of the number of sexual partners, the prevalence of the viruses and the infectivity per contact. Using maximum likelihood estimation theory and data from a prospective study of registered female prostitutes in Dakar, Senegal, we estimate and compare the infectivities of HIV-1 and HIV-2. Graphical goodness-of-fit methods are used to show that our model fits the data well. We find that in male-to-female transmission HIV-1 is significantly more infectious than HIV-2. This finding is consistent with other data from laboratory and epidemiologic studies comparing the biology of HIV-1 and HIV-2.

Acquired Immunodeficiency Syndrome↗

Humoral aspects of anti-HIV immune responses in Zairians with AIDS: lower antigenemia does not correlate with immune complex levels.

Serological patterns of anti-HIV immune responses of 150 HIV-infected (65 asymptomatic, 19 ARC, 66 AIDS) and 150 HIV-negative healthy Zairians were studied to determine the clinical significance of p24 antigen, and anti-p24 antibody, particularly in relation to p24 relative binding capacity (RBC) and circulating immune complexes (CICs). Levels of p24 antigen, anti-p24 antibody titers, and p24 RBC were evaluated by means of enzyme-linked immunosorbent assay (ELISA). Circulating immune complexes were measured by C1q-binding assay. Human immunodeficiency virus CICs were detected by polyethylene glycol (PEG) precipitation followed by 6 M guanidinium lysis, ELISA, Western blot, or radioimmunoprecipitation of the lysed precipitates. Immunoglobulin levels for IgG, IgM, IgA, and beta 2-microglobulin (beta 2-M) were quantified in all study participants by laser nephelometry and ELISA. All immunoglobulin levels were significantly elevated among HIV-positive vs. HIV-negative individuals. Immunoglobulin levels correlated well with disease progression among infected patients. Similarly, beta 2-M levels were significantly higher in HIV-positive vs. HIV-negative individuals and correlated well with progression to AIDS. Free p24 antigen in serum was detected in 1.33% of all patients. However, p24 reactivity increased to 6% (9 of 150 cases) after PEG precipitation and CIC dissociation. There was a good correlation between p24 reactivity and disease development. High titers of anti-p24 antibody (> 44,100) occurred in at least 80% of all patients, and did not correlate with disease stage. Similarly, more than 60% of patients had high levels of p24 RBC.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Prevalence and risk determinants of human immunodeficiency virus type 2 (HIV-2) and human immunodeficiency virus type 1 (HIV-1) in west African female prostitutes.

The authors studied the prevalence and risk determinants for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) in female prostitutes from Dakar (1985-1990), Ziguinchor (1987-1990), and Kaolack (1987-1990), Senegal, West Africa. Each cohort showed a distinct distribution of HIVs: 10.0% HIV-2 and 4.1% HIV-1 in Dakar, 38.1% HIV-2 and 0.4% HIV-1 in Ziguinchor, and 27.4% HIV-2 and 1.3% HIV-1 in Kaolack. In 1,275 female prostitutes from Dakar, increase years of sexual activity and a history of scarification were associated with HIV-2 seropositivity. In contrast, HIV-1 seroprevalence was associated with a shorter duration of prostitution and a history of hospitalization. In 278 female prostitutes from Ziguinchor, HIV-2 seroprevalence was associated with women of Guinea-Bissau nationality and increased years of sexual activity. In 157 female prostitutes from Kaolack, HIV-2 seroprevalence was associated with increased years of sexual activity and a history of never using condoms. The authors also studied the risk determinants for HIV-2 in the 1,280 Senegalese prostitutes pooled from all three sites. Controlling for ethnic group, women from Ziguinchor and Kaolack were more likely to be HIV-2 seropositive as compared with women from the Dakar site. Increased years of sexual activity were associated with HIV-2 seropositivity, while a history of excision and BCG vaccinations decreased the risk of HIV-2 infection.

Adult↗

Site-directed serology using synthetic oligopeptides representing the C-terminus of the external glycoproteins of HIV-1, HIV-2, or SIVmac may distinguish subtypes among primate lentiviruses.

In this study the presence of a highly immunogenic domain located at the C-terminus of the external glycoproteins (EGP) of human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIVMAC) is shown using synthetic oligopeptides as antigens in enzyme immunoassays. This epitope is probably located within the last 13 and 15 residues of the EGP of HIV-1 and HIV-2, respectively. The C terminal epitope of the EGP of SIVMAC may involve residues located more upstream. Among the HIV-2/SIV serotype, we observed that the reactivity to the C-terminal epitope of gp120 was dependent of both species and geographical origin of the samples tested. It seems that this gp 120 C-terminal epitope could distinguish subtypes among the HIV-2/SIV serotype. Further studies, using site-directed enzyme immunoassays with synthetic peptides representing the C-terminus of the EGP derived from a wide variety of HIV2/SIV strains must be performed to confirm this observation. These kinds of assays may constitute important tools for use in seroepidemiological studies and broaden our understanding of the distribution and phylogenetic relationship of primate lentiviruses.

Amino Acid Sequence↗

HIV-2 link to AIDS in West Africa.

To date, very little is known concerning the clinical spectrum of human immunodeficiency virus type 2 (HIV-2) infection, and the question as to whether HIV-2 will ultimately prove to be as pathogenic as human immunodeficiency virus type I (HIV-1) remains, as yet, unanswered. We reviewed the currently available reports of HIV-2 infection to assess what is known about the extent of HIV-2 pathogenicity as it compares to HIV-1 pathogenicity. There is evidence that HIV-2 is associated with AIDS. Most of this evidence, however, comes from descriptive case-report type data that do not meet the basic requirements for defining causality. The most significant problems are the lack of control groups and the absence of a documented temporal relationship with HIV-2 infection preceding the development of AIDS. Comparisons of the epidemiology and disease association between HIV-1 and HIV-2 in Africa may suggest relative pathogenic effects. Although certain comparisons between HIV-2 and HIV-1 are difficult to make, we conclude on the basis of existing data that the pathogenic effects and the natural history of HIV-2 are distinct from those of HIV-1.

Acquired Immunodeficiency Syndrome↗

Increased peripheral lymphocytes, lymphoid hepatitis and anaemia in African vervet monkeys seropositive to retroviruses.

Wild-caught African Vervet monkeys are commonly infected by Simian T-lymphotropic virus I (STLV1) and Simian immunodeficiency virus (SIV), yet the natural histories of these infections are largely unknown. Seropositivity was associated with increased total, T and atypical lymphocytes. In seropositive females there was mild, normocytic, normochromic anaemia. Lymphoid hepatitis was present in seven seropositive cases. African Vervets used in biomedical research, vaccine production and organ transplantation research are often infected by exogenous retroviruses which can be oncogenic and immunosuppressive in captive monkeys. Elimination of these infections may be possible by breeding Vervets in captivity.

Anemia↗

A STLV-III related human retrovirus, HTLV-IV: analysis of cross-reactivity with the human immunodeficiency virus (HIV).

A category of viruses has been identified which is related to human immunodeficiency virus (HIV) but is more closely related to a group of simian retroviruses (STLV-III). These viruses named HTLV-IV, LAV-II, or SBL-6669, are prevalent in West-Africa. In this study, we analysed the cross-reactivity at the protein level between HTLV-IV and HIV (HTLV-IIIB). The results indicate that most people infected with HTLV-IV have antibodies that react to the major gag protein of HIV p 24. There is also a high degree of immunologic cross-reactivity between the pol gene products of HIV and HTLV-IV. Among these the endonuclease/integrase is more conserved than the reverse transcriptase. In contrast, the envelope glycoproteins that are the most frequently detected antigens by antibodies from exposed individuals are serotype specific. These data make the env gene products the most interesting antigens for serotype specific diagnosis of human retroviruses infections.

Antibodies, Viral↗