Papa Salif Sow

The Senegalese government's highly active antiretroviral therapy initiative: an 18-month follow-up study.

ObjectiveTo study the feasibility, effectiveness, adherence, toxicity and viral resistance in an African government HAART initiative. MethodsA prospective observational cohort study started in Dakar in August 1998. Initial treatment consisted of two nucleoside reverse transcriptase inhibitors and one protease inhibitor. The patients attended monthly medical examinations. Plasma HIV-1 RNA and CD4 cell counts were determined at baseline and every 6 months. Intention-to-treat analyses were performed. ResultsFifty-eight treatment-naive patients, mostly infected by HIV-1 strain CRF02-AG, were enrolled. Most were at an advanced stage of HIV disease (86.2% had AIDS). Adherence was good in 87.9% of patients and treatment was effective in most of them. Thus, HIV-1 RNA was undetectable in 79.6, 71.2, 51.4 and 59.3% of patients at months 1, 6, 12 and 18, respectively and the median viral load reduction was ∼2.5 log10 copies/ml. The CD4 cell count rose by a median of 82, 147 and 180 × 106 cells/l at months 6, 12 and 18, respectively. At the same time points, the cumulative probability of remaining alive or free of new AIDS-defining events was 94.8, 85.0 and 82.3%. Most adverse effects (80.8%) were mild or moderate and only two cases of drug resistance occurred. ConclusionThis study shows that HAART is feasible and well tolerated in African patients. Clinical and biological results were comparable to those seen in western cohorts, despite differences in the HIV-1 subtype distribution and an advanced disease stage when the treatment was initiated. Contrary to other recent studies in Africa, viral resistance rarely emerged.

Mortality and causes of death in adults receiving highly active antiretroviral therapy in Senegal: a 7-year cohort study.

Objectives:To evaluate survival and investigate causes of death among HIV-1 infected adults receiving HAART in Senegal. Design:An observational prospective cohort. Methods:Mortality was assessed in the first patients enrolled between August 1998 and April 2002 in the Senegalese antiretroviral drug access initiative. First-line regimen combined two nucleoside reverse transcriptase inhibitors and either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor. The most likely causes of death were ascertained through medical records or post-mortem interviews (verbal autopsy). Results:Four hundred and four patients (54.7% women) were enrolled in the study and were followed for a median of 46 months (interquartile range: 32–57 months) after HAART initiation. At baseline, 5% were antiretroviral therapy (ART) non-naive, 39 and 55% were respectively at CDC stage B and C, median age, CD4 cell count and viral load were 37 years, 128 cells/μl and 5.2 log cp/ml, respectively. Ninety-three patients died during follow-up and the overall incidence rate of death was 6.3/100 person-years [95% confidence interval (CI), 5.2–7.7]. During the first year after HAART initiation, 47 patients died and seven were lost to follow-up, yielding to a probability of dying of 11.7% (95% CI, 8.9–15.3%). The death rate, which was highest during the first year after HAART initiation, decreased with time yielding a cumulative probability of dying of 17.4% (95% CI, 13.9–21.5%) and 24.6% (95% CI, 20.4–29.4%) at 2 and 5 years. Causes of death were ascertained in 76 deaths. Mycobacterial infections, neurotropic infections and septicaemia were the most frequent likely causes of death. Conclusions:This study underlines the early mortality pattern after HAART initiation and highlights the leading role of mycobacterial infections in the causes of death.

Increased risk of high-grade cervical squamous intraepithelial lesions and invasive cervical cancer among African women with human immunodeficiency virus type 1 and 2 infections.

To assess the risk of prevalent high-grade cervical squamous intraepithelial lesions (HSILs) or invasive cervical cancer (ICC) associated with human immunodeficiency virus (HIV) type 1, HIV-2, and human papillomavirus (HPV) infections, HIV load, and CD4 cell count, we studied 4119 women attending an outpatient clinic in Senegal. HIV infection was associated with increased rates of cervical infection with high-risk HPVs. Among women infected with high-risk HPVs, those with HIV-1 (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.0-4.8), HIV-2 (OR, 6.0; 95% CI, 2.1-17.1), or dual HIV infection (OR, 8.0; 95% CI, 2.0-31.5) were more likely to have HSILs or ICC diagnosed than were HIV-negative women; this association was not observed among women not infected with high-risk HPVs. Among women with HIV, higher HIV plasma RNA loads and lower CD4 cell counts were associated with high-risk HPV infection and degree of cervical abnormality. Furthermore, HIV-2-positive women were more likely to have HSILs (OR, 3.3; 95% CI, 0.9-12.4) or ICC (OR, 7.9; 95% CI, 1.1-57) than were HIV-1-positive women.

Equal Plasma Viral Loads Predict a Similar Rate of CD4± T Cell Decline in Human Immunodeficiency Virus (HIV) Type 1- and HIV-2-Infected Individuals from Senegal, West Africa

Human immunodeficiency virus (HIV) type 2 infection is characterized by slower disease progression to acquired immunodeficiency syndrome than results from HIV-1 infection. To better understand the biological factors underlying the different natural histories of infection with these 2 retroviruses, we examined the relationship between HIV RNA and DNA levels and the rate of CD4(+) T cell decline among 472 HIV-1- and 114 HIV-2-infected individuals from Senegal. The annual rate of CD4(+) T cell decline in the HIV-2 cohort was approximately one-fourth that seen in the HIV-1 cohort. However, when the analysis was adjusted for baseline plasma HIV RNA level, the rates of CD4(+) T cell decline per year for the HIV-1 and HIV-2 cohorts were similar (a rate increase of approximately 4% per year for each increase in viral load of 1 log(10) copies/mL). Therefore, plasma HIV load is predictive of the rate of CD4(+) T cell decline over time, and the correlation between viral load and the rate of decline appears to be similar among all HIV-infected individuals, regardless of whether they harbor HIV-1 or HIV-2.

To stem HIV in Africa, prevent transmission to young women.

Over the years community-based studies have shown that higher proportions of young women (15-19 years) in Africa are already infected with HIV compared with their male counterparts. This is likely because non-response in HIV surveys is higher in men than women and those who are repeatedly absent or who refuse clinical testing may be more likely to be HIV infected. Moreover HIV is more easily transmitted from men to women than vice versa. Patterns of sexual mixing may also account for differences in the infection levels between men and women evidenced in the frequent sexual relationships between younger women and older men. Men also appear to be less to use condoms with young female partners. In this perspective the success in cutting back the devastation caused by HIV and AIDS in east and southern Africa depends upon the successful prevention of transmission of HIV to young women while focusing on both men and women. Thus prevention programs provided to young women and their older partners in a high-HIV prevalence epidemic should aim to: 1) reduce early exposure to risky sex 2) reduce likelihood of transmission per sexual act and 3) reduce age difference between partners.

HIV prevalence, previous HIV testing, and condom use with clients and regular partners among Senegalese commercial sex workers

Objectives: To assess HIV prevalence and risk factors for HIV infection, to investigate condom use among registered female commercial sex workers (CSWs) in Senegal, West Africa, and to examine the association between previous HIV testing, knowledge of HIV serostatus and condom use with both regular sex partners and clients within this population. Methods: A cross-sectional study was conducted at three sexually transmitted disease clinics among 1052 Senegalese registered CSWs between 2000 and 2004. Inperson interviews soliciting information concerning demographic characteristics, medical history, sexual behaviour with clients and regular partners, and previous HIV testing history were performed. Blood samples were collected for determination of HIV-1 and/or HIV-2 serostatus. Multivariable, Poisson and log-binomial models were used to calculate prevalence ratios. Results: The overall HIV prevalence was 19.8%. Over 95% of CSWs reported always using a condom with clients, but only 18% reported always using a condom with their regular partners. A history of previous HIV testing was not associated with condom use with clients (adjusted prevalence ratio (APR) = 0.98, 95% confidence intervals, CI: 0.90 to 1.06). However, prior HIV testing was associated with decreased condom use with their regular partners (APR = 0.44, 95% CI: 0.28 to 0.69), especially in women who tested HIV negative (APR = 0.17, 95% CI: 0.08 to 0.36). Conclusions: CSWs in Senegal have a high HIV prevalence; therefore preventing HIV transmission from this population to the general population is important. Condom use with regular partners is low among registered CSWs in Senegal, and a prior HIV negative test is associated with even less condom use with regular partners. Intervention efforts to increase condom use with regular sexual partners are needed.

Combination of Tumor Site–Located CTL-Associated Antigen-4 Blockade and Systemic Regulatory T-Cell Depletion Induces Tumor-Destructive Immune Responses

Accumulating data indicate that tumor-infiltrating regulatory T cells (Treg) are present in human tumors and locally suppress antitumor immune cells. In this study, we found an increased Treg/CD8 ratio in human breast and cervical cancers. A similar intratumoral lymphocyte pattern was observed in a mouse model for cervical cancer (TC-1 cells). In this model, systemic Treg depletion was inefficient in controlling tumor growth. Furthermore, systemic CTL-associated antigen-4 (CTLA-4) blockade, an approach that can induce tumor immunity in other tumor models, did not result in TC-1 tumor regression but led to spontaneous development of autoimmune hepatitis. We hypothesized that continuous expression of an anti-CTLA-4 antibody localized to the tumor site could overcome Treg-mediated immunosuppression and locally activate tumor-reactive CD8+ cells, without induction of autoimmunity. To test this hypothesis, we created TC-1 cells that secrete a functional anti-CTLA-4 antibody (TC-1/alphaCTLA-4-gamma1 cells). When injected into immunocompetent mice, the growth of TC-1/alphaCTLA-4-gamma1 tumors was delayed compared with control TC-1 cells and accompanied by a reversion of the intratumoral Treg/CD8 ratio due to an increase in tumor-infiltrating IFNgamma-producing CD8+ cells. When local anti-CTLA-4 antibody production was combined with Treg inhibition, permanent TC-1 tumor regression and immunity was induced. Importantly, no signs of autoimmunity were detected in mice that received local CTLA-4 blockade alone or in combination with Treg depletion.

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.

Prevalence of specific types of human papillomavirus and cervical squamous intraepithelial lesions in consecutive, previously unscreened, West-African women over 35 years of age†

Previous studies among women worldwide have demonstrated that infection with specific types of human papillomaviruses (HPV) is central to the pathogenesis of cervical neoplasia. There is little data, however, concerning the prevalence of specific HPV types and the association of each type with cervical neoplasia among women in sub‐Saharan Africa, who remain at very high risk of cervical cancer. We studied 2,065 consecutive patients aged 35 years or older, presenting to community health clinics in Dakar and Pikine, West Africa, who had not been screened previously for cytologic abnormalities or HPV. Cytologic diagnosis and HPV detection were accomplished using a ThinPrep Pap and a polymerase chain reaction‐based reverse‐line strip assay, respectively. Odds ratios (OR) and associated 95% confidence intervals (CI) were estimated using polynomial logistic regression. Cytologic abnormalities were found in 426 women (20%), including 254 (12%) with atypical squamous cells of undetermined significance, 86 (4%) with low‐grade squamous intraepithelial lesions, 66 (3%) with high‐grade squamous intraepithelial lesions (HSIL) and 20 (1%) with invasive cancer. HPV infection was detected in 18%. Among women with negative cytologic findings, the prevalence of high risk but not low risk HPV types increased with age. HPV16 (2.4%) and HPV58 (1.6%) were the most frequently detected HPV types in this population, as well as being the most strongly associated with risk of HSIL/cancer (HPV16: OR = 88, 95% CI = 39–200; HPV58: OR = 51, 95% CI = 16–161). These data suggest that in addition to HPV16, HPV58 should be considered in the strategic planning of vaccination against cervical cancer in this geographic region.

Sensitivity of IFN-γ Release Assay to Detect Latent Tuberculosis Infection Is Retained in HIV-Infected Patients but Dependent on HIV/AIDS Progression

Background Detection and treatment of latent TB infection (LTBI) in HIV infected individuals is strongly recommended to decrease morbidity and mortality in countries with high levels of HIV. Objective To assess the validity of a newly developed in-house ELISPOT interferon-γ release assay (IGRA) for the detection of LTBI amongst HIV infected individuals, in comparison with the Tuberculin Skin Test (TST). Methodology/Principal Findings ESAT6/CFP10 (EC) ELISPOT assays were performed, together with a TST, in 285 HIV infected individuals recruited in HIV clinics in Dakar, Senegal, who had no signs of active TB at time of enrolment. Thirty eight of the subjects (13.3%) failed to respond to PHA stimulation and were excluded from the analysis. In the 247 remaining patients, response to PHA did not vary according to CD4 cell count categories (p = 0.51). EC ELISPOT was positive in 125 (50.6%) subjects, while 53 (21.5%) had a positive TST. Concordance between EC ELISPOT and TST was observed in 151 patients (61.1%) (kappa = 0.23). The proportion of subjects with a positive response to the EC ELISPOT assay decreased with declining CD4 counts (p trend = 0.001), but were consistently higher than the proportion of TST responders. In multivariate analysis, the risk of being EC-ELISPOT positive in HIV infected individuals was associated with age, CD4 count and HIV-1 strain. Conclusion Our study indicates that IGRAs using M. tuberculosis specific antigens are likely to retain their validity for the diagnosis of LTBI among HIV positive individuals, but may be impaired by T-cell anergy in severely immuno-suppressed individuals.