Aissatou Guèye-Ndiaye

Lower Human Immunodeficiency Virus (HIV) Type 2 Viral Load Reflects the Difference in Pathogenicity of HIV-1 and HIV-2

Human immunodeficiency virus type 2 (HIV-2) is less pathogenic than HIV type 1 (HIV-1), but the mechanisms underlying this difference have not been defined. We developed an internally controlled quantitative reverse transcriptase-polymerase chain reaction to measure HIV-2 viral load and determined levels of plasma virus in a cohort of registered commercial sex workers in Dakar, Senegal. The assay has a lower limit of detection of 100 copies/mL and is linear over 4 logs. HIV-2 viral RNA was detectable in 56% of all samples tested; the median load was 141 copies/mL. Levels of viral RNA in the plasma were inversely related to CD4+ cell counts. HIV-2 and HIV-1 viral loads were compared among the seroincident women in the cohort; the median viral load was 30x lower in the HIV-2-infected women (P<.001, Wilcoxon rank sum test), irrespective of the length of time infected. This suggests that plasma viremia is linked to the differences in the pathogenicity of the 2 viruses.

Low Plasma Human Immunodeficiency Virus Type 2 Viral Load Is Independent of Proviral Load: Low Virus Production In Vivo

ABSTRACT Levels of virus in the plasma are closely related to the pathogenicity of human immunodeficiency virus type 1 (HIV-1). HIV-2 is much less pathogenic than HIV-1, and infection with HIV-2 leads to significantly lower plasma viral load. To identify the source of this difference, we measured both viral RNA and proviral DNA in matched samples from 34 HIV-2-infected individuals. Nearly half had undetectable viral RNA loads (<100 copies/ml), but levels of proviral DNA were relatively high and confirmed that quantities of provirus in HIV-1 and HIV-2 infection were similar. Overall, HIV-2 proviral DNA load did not correlate with viral RNA load, and higher viral RNA load was associated with increased production of plasma virus from the proviral template. These results suggest that low viral load in HIV-2 infection is due to decreased rates of viral production, rather than differences in target cell infectivity.

Ordinary and Opportunistic Enteropathogens Associated with Diarrhea in Senegalese Adults in Relation to Human Immunodeficiency Virus Serostatus

Abstract Objectives: A survey was conducted in Dakar, Senegal, to identify major types and prevalences of bacteria, parasites, fungi, and Rotaviruses associated with diarrhea in relation to human immunodeficieny virus (HIV) serostatus with the goal to provide guidance to physicians for case management. Methods: Etiologic agents were identified in a case-control study: cases were HIV-infected patients with diarrhea (HIV+ D+) and HIV seronegative patients with diarrhea (HIV− D+); controls were HIV-infected patients without diarrhea (HIV+ D−) and seronegative controls without diarrhea (HID− D−). Ordinary enteric pathogens were identified by conventional methods. Different Escherichia coli pathotypes were characterized by polymerase chain reaction (PCR), identification of HEp-2 cell adherence pattern, Sereny test, GIvl1-ELISA, and the suckling mouse assay. Opportunistic parasites, such as Cryptosporidium and Microsporidium, were identified by the Kinyoun method and trichromic stain of Weber, respectively. Rotaviruses were identified with a commercial latex agglutination kit. Antimicrobial susceptibility testing was carried out by the disk diffusion method. Results: Among the 594 patients examined, 158 were HIV+ D+, 121 were HIV− D+, 160 were HIV+ D−, and 155 were HIV− D−. The main etiologies of diarrhea were different according to HIV serostatus of patients. In immunocompetent adults the main causes of diarrhea were Shigella sp (12.4%), Entamoeba histolytica (10.7%), Salmonella enterica (6.6%), and Giardia (4.9%). In the immunocompromised host the more frequent pathogens were enteroaggregative E. coli (19.6%), Microsporidium (9.4%), Cryptosporidium sp (8.2%), Rotavirus (8.2%), Shigella sp (7.6%), Candida albicans (7.6%), E. histolytica (5.1%), S. enterica (4.4%), and Isospora belli (4.4%). Also, Blastocystis hominis has to be considered as an opportunistic parasite, because it was identified only in HIV-infected patients, with higher prevalence in adults with diarrhea (2.5% in HIV+ D+ patients; 0.6% in HIV+ D− patients). High level of asymptomatic carriage of Ascaris lumbricoides and Trichuris trichiura and some cases of multiple infections were observed. Fungi, Cryptosporidium sp and Microsporidium sp, were often identified in patients with low CD4 counts (range, 79–250 cells/mL). Independently from HIV-serostatus, CD4 count was lower in diarrheic persons, suggesting that diarrhea is a debilitating illness and that effective management of diarrhea can prevent immunosuppression. Isolated enteropathogenic strains displayed high resistance to most antibiotics used in Senegal for treating diarrhea (ampicillin, tetracycline, cotrimoxazole); they were susceptible to amikacin, gentamicin, and norfloxacin. Conclusion: These epidemiologic data suggest that guidelines for the management of diarrhea during HIV infection in Dakar should be updated.

Religion and protective behaviours towards AIDS in rural Senegal.

ObjectivesTo describe the association between religion and factors related to sexually transmitted diseases (STD)/AIDS in a country where religious leaders were involved early in prevention. DesignA cross-sectional study conducted in a rural area in central Senegal. MethodsQuestionnaire-based interviews of a random sample of 858 adults from the general population aged 15–59 years and in-depth interviews of four religious leaders and 50 people. ResultsSeventy-six per cent of the respondents were Muslim, 24% Catholic, 1% Animist and 0.2% Protestant. A total of 86% of men and 87% of women reported religion to be very important to them. Important prevention-related variables were inversely associated with the importance of religion. Men who considered religion to be very important were less likely to cite AIDS as a major health problem [odds ratio (OR) 0.4, P = 0.008] and were less likely to feel at risk of getting HIV (OR 0.5, P = 0.0005). Women who considered religion to be very important were less likely to report an intention to change to protect themselves from AIDS (OR 0.2, P = 0.0001), less likely to report having discussed AIDS with others (OR 0.4, P = 0.01) and much more likely to feel at risk of getting HIV (OR 9.3, P = 10−4). Individuals who considered religion to be very important were not more likely to report intending to or actually having become faithful to protect themselves from AIDS. ConclusionThese findings stress the need to intensify the involvement of religious authorities in HIV/STD prevention at the local level.

Comparison of Heterologous Neutralizing Antibody Responses of Human Immunodeficiency Virus Type 1 (HIV-1)- and HIV-2-Infected Senegalese Patients: Distinct Patterns of Breadth and Magnitude Distinguish HIV-1 and HIV-2 Infections

ABSTRACT Neutralizing antibody responses against heterologous isolates in human immunodeficiency virus type 1 (HIV-1) and HIV-2 infections were compared, and their relationships with established clinical markers of progression were examined. Neutralizing responses against 7 heterologous primary isolates and 1 laboratory strain were compared between 32 untreated HIV-1-infected subjects and 35 untreated HIV-2-infected subjects using a pseudotyped reporter virus assay. The breadth of the neutralizing response, defined as the proportion of panel viruses positively neutralized by patient plasma, was significantly greater among HIV-2-infected subjects than among HIV-1-infected subjects. Notably, for fully one-third of HIV-2 subjects, all viruses were effectively neutralized in our panel. Magnitudes of responses, defined as reciprocal 50% inhibitory concentration (IC50) titers for positive reactions, were significantly greater among HIV-1-infected subjects than among HIV-2-infected subjects. When plasma samples from HIV-1 patients were tested for cross-neutralization of HIV-2 and vice versa, we found that these intertype responses are very rare and their prevalences comparable in both HIV-1 and HIV-2 infection. The significantly higher magnitude of heterologous responses for HIV-1 compared to HIV-2 prompted us to examine associations with viremia, which is known to be significantly higher in HIV-1 infection. Importantly, there was a significant positive correlation between the IC50 titer and viral load within both the HIV-1 and HIV-2 groups, suggesting heterologous antibodies may be driven by viral replication. We conclude that HIV-2 infection is characterized by a broad, low-magnitude intratype neutralization response, while HIV-1 is characterized by a narrower but higher-magnitude intratype response and that a significant positive association between the IC50 titer and viremia is common to both HIV-1 and HIV-2 infections.

Genetic analysis of HIV type 2 in monotypic and dual HIV infections.

A significant level of genetic variation among HIV-1 and HIV-2 has been described. The interaction of specific HIV-2 subtypes with HIV-1 may serve to identify potential biological properties associated with dual infection. To genetically characterize the HIV-2 strains circulating in Senegal and their relationship to coinfection with HIV-1, we sequenced the HIV-2 envelope C2-C3 region of 12 subjects coinfected with HIV-1 and HIV-2 and 9 subjects singly infected with HIV-2. The phylogenetic analysis showed that all subjects were infected with HIV-2 subtype A, confirming its predominance in West Africa. We did not observe specific sequences or genetic clustering based on coinfection status.

Viral Dynamics of Primary HIV-1 Infection in Senegal, West Africa

BACKGROUND Few studies have addressed primary human immunodeficiency virus (HIV) type 1 infection in sub-Saharan Africa, where the epidemic is of a predominantly heterosexual character and is caused by different subtypes. The present study examines the dynamics of viral replication in subjects infected with various HIV-1 subtypes. METHODS Seven hundred fifty-two HIV-negative Senegalese women at high risk for infection were monitored every 3 months for acute/early HIV infection; 26 infections were identified (23 HIV-1 and 3 HIV-2), with an HIV-1 incidence rate of 3.23 cases/person-years observation. Multiple viral-load measurements were taken for all seroconverters. RESULTS The mean+/-standard deviation viral load for all subjects during the early stage of infection was 4.13+/-0.66 log10 copies/mL, with an overall decrease of 0.22 log10 copies/mL after the early stage; the viral set point was reached after 12 months of infection. Most subjects had relatively low viral loads during the early stage of infection. HIV-1 CRF02_AG-infected women had a significantly higher mean viral load during the early stage of infection (mean +/- SD, 4.45+/-0.60 log(10) copies/mL) than did non-HIV-1 CRF02_AG-infected women (mean+/-SD, 3.78+/-0.46 log(10) copies/mL) (P=.008). None of the subjects reported symptoms consistent with primary HIV-1 infection. CONCLUSION Our findings in Senegalese women differ from what have been described for primary HIV-1 infection. Further investigations of primary infections with non-B subtypes are warranted, to better characterize their differences with primary infections with subtype B.

Molecular Epidemiology of Human Immunodeficiency Virus Type 1 Sub-Subtype A3 in Senegal from 1988 to 2001

ABSTRACT The global human immunodeficiency virus (HIV)epidemic is characterized by significant genetic diversity in circulating viruses. We have recently characterized a group of viruses that form a distinct sub-subtype within the subtype A radiation, which we have designated HIV type 1 (HIV-1) sub-subtype A, circulating in West Africa. A prospective study of a cohort of female sex workers (FSW) in Dakar, Senegal over an 18-year period indicated that an A3-specific sequence in the C2-V3 region of the env gene was found in 46 HIV-1-infected women. HIV-1 sub-subtype A3 appeared in the FSW population as early as 1988 and continued to be transmitted as of 2001. We also found that HIV-1 A3 is not confined to the FSW cohort in Senegal but is also circulating in the general population in Dakar. Furthermore, analyses of viral sequences from a few other West and Central African countries also demonstrated evidence of HIV-1 A3 sequence in isolates from HIV-1-infected people in Ivory Coast, Nigeria, Niger, Guinea Bissau, Benin, and Equatorial Guinea. Overall, because of the evidence of sub-subtype A3 in the general population in Senegal, as well as in a few neighboring West and Central African countries, along with the increasing incidence of infection with A3-containing viruses in the Dakar high-risk FSW population, we feel that HIV-1 sub-subtype A3 viruses are important to distinguish and monitor.

Treponemal infection rates, risk factors and pregnancy outcome in a rural area of Senegal

A rural population of east Senegal has been under demographic surveillance for more than 30 years and a high rate of infertility has been reported. The aim of the study is to describe HIV and treponemal infection epidemiology and association with outcome of pregnancy in a population of rural Senegal. A population-based cross-sectional study was conducted among 952 randomly-selected adults of a rural community of Senegal. No participant was found to be infected with HIV, 11% had evidence of past syphilis and 5% of active syphilis. Active syphilis was associated among men with age, long-term mobility and having partners in an urban area in the last 12 months and among women with being divorced or widowed. No association was found between past or active syphilis and abortion or stillbirth but women aged 40 and more with past or active syphilis were significantly more likely to have had no history of gestation than women with no evidence of syphilis infection. In conclusion our results call for more research to understand the epidemiology of treponemal infection and to elucidate types of Treponema pallidum involved.