Abraham Alabi

Body Mass Index at Time of Hiv Diagnosis: A Strong and Independent Predictor of Survival

BackgroundIdentification of basic prognostic indicators of HIV infection is essential before widespread antiretroviral therapy can be implemented in low-technology settings. This study assessed how well body mass index (BMI:kg/m2) predicts survival. MethodsBMI within 3 months of HIV diagnosis was obtained from 1657 patients aged ≥15 years, recruited in a seroprevalent clinical cohort in The Gambia since 1992 and followed up at least once. Baseline CD4+ counts and clinical assessment at time of diagnosis were done. ResultsThe mortality hazard ratio (HR) of those with a baseline BMI <18 compared with those with a baseline BMI ≥18 was 3.4 (95% CI, 3.0–3.9). The median survival time of those presenting with a BMI <16 was 0.8 years, in contrast to a median survival of 8.9 years for those with a baseline BMI ≥22. Baseline BMI <18 remained a highly significant independent predictor of mortality after adjustment for age, sex, co-trimoxazole prophylaxis, tuberculosis, reported wasting at diagnosis, and baseline CD4+ cell count (adjusted HR = 2.5, 95% CI 2.0–3.0). Sensitivity and specificity of baseline BMI <18 was comparable to that of a CD4+ count <200 in predicting mortality within 6 months of diagnosis. DiscussionBMI at diagnosis is a strong, independent predictor of survival in HIV-infected patients in West Africa. In the absence of sophisticated clinical and laboratory support, BMI may also prove a useful guide for deciding when to initiate antiretroviral therapy.

Mortality of HIV-1, HIV-2 and HIV-1/HIV-2 dually infected patients in a clinic-based cohort in The Gambia.

ObjectiveTo assess and compare the mortality rates of patients with HIV-1, HIV-2 or both infections (HIV-D) in the same population. DesignClinic-based cohort study. MethodsHIV-seropositive patients aged 15 years and older who attended the Medical Research Council clinics in Fajara between May 1986 and September 1997 were recruited. Clinical assessment using the Karnofsky score, CDC cell staging, WHO staging, and CD4 cell counts was performed at baseline. Patients attended clinic every 3 months; if they did not attend, they were visited at home by field workers to ascertain survival status. No patient was on antiretroviral therapy during the study period. ResultsData from 1519 HIV-positive adult patients were analysed. A total of 746 patients had HIV-1, 666 HIV-2, and 107 patients had HIV-D. A total of 828 patients (55%) died, and 161 (11%) were lost to follow-up. The median follow-up was 12 months (range 0–128). CD4 cell counts were available for 894 patients. Compared with HIV-1, the adjusted hazards ratio for mortality in the CD4 cell count category 500 cells/μl or greater was 0.50 for HIV-2 (95% CI 0.28–0.88) and 1.27 (95% CI 0.51–3.7) for HIV-D. Among those with CD4 cell counts less than 500 cells/μl the mortality rates in HIV-2 and HIV-D were similar to those in HIV-1. DiscussionHIV-2-infected patients with CD4 cell counts of 500 cells/μl and greater had a significantly lower mortality rate than HIV-1-infected patients. HIV-2-infected patients with advanced disease had the same poor prognosis as patients with HIV-1. Dually infected patients had mortality rates similar to HIV-1.

Maintenance of HIV-Specific CD4+ T Cell Help Distinguishes HIV-2 from HIV-1 Infection

Unlike HIV-1-infected people, most HIV-2-infected subjects maintain a healthy CD4+ T cell count and a strong HIV-specific CD4+ T cell response. To define the cellular immunological correlates of good prognosis in HIV-2 infection, we conducted a cross-sectional study of HIV Gag-specific T cell function in HIV-1- and HIV-2-infected Gambians. Using cytokine flow cytometry and lymphoproliferation assays, we show that HIV-specific CD4+ T cells from HIV-2-infected individuals maintained proliferative capacity, were not terminally differentiated (CD57−), and more frequently produced IFN-γ or IL-2 than CD4+ T cells from HIV-1-infected donors. Polyfunctional (IFN-γ+/IL-2+) HIV-specific CD4+ T cells were found exclusively in HIV-2+ donors. The disparity in CD4+ T cell responses between asymptomatic HIV-1- and HIV-2-infected subjects was not associated with differences in the proliferative capacity of HIV-specific CD8+ T cells. This study demonstrates that HIV-2-infected donors have a well-preserved and functionally heterogeneous HIV-specific memory CD4+ T cell response that is associated with delayed disease progression in the majority of infected people.

Robust Gag-specific T cell responses characterize viremia control in HIV-2 infection

HIV-2 infection in the majority of infected subjects follows an attenuated disease course that distinguishes it from infection with HIV-1. Antigen-specific T cells are pivotal in the management of chronic viral infections but are not sufficient to control viral replication in HIV-1-positive subjects, and their function in HIV-2 infection is not fully established. In a community-based cohort of HIV-2 long-term nonprogressors in rural Guinea-Bissau, we performed what we believe is the first comprehensive analysis of HIV-2-specific immune responses. We demonstrate that Gag is the most immunogenic protein. The magnitude of the IFN-gamma immune response to the HIV-2 proteome was inversely correlated with HIV-2 viremia, and this relationship was specifically due to the targeting of Gag. Furthermore, patients with undetectable viremia had greater Gag-specific responses compared with patients with high viral replication. The most frequently recognized peptides clustered within a defined region of Gag, and responses to a single peptide in this region were associated with low viral burden. The consistent relationship between Gag-specific immune responses and viremia control suggests that T cell responses are vital in determining the superior outcome of HIV-2 infection. A better understanding of how HIV-2 infection is controlled may identify correlates of effective protective immunity essential for the design of HIV vaccines.

Plasma RNA viral load predicts the rate of CD4 T cell decline and death in HIV-2-infected patients in West Africa.

ObjectiveTo examine whether the levels of plasma RNA and DNA provirus predict the rate of CD4 cell decline and patient death. DesignRetrospective analysis of HIV-2 cohort subjects. MethodsFifty-two subjects were recruited between January 1991 and December 1992. HIV-2 RNA levels in plasma and DNA levels in peripheral blood mononuclear cells (PBMC) were measured using in-house quantitative PCR assays. The annual rate of CD4 cell decline was calculated using the least-squares method. The survival data on 31 December 1997 were used. ResultsThe mean percentage of CD4 cells at baseline was 30.7 (SD, 9.5). In a linear regression model, the annual rate of CD4 cell decline was 1.76 CD4% faster for every increase in one log10 RNA copies/ml [95% confidence interval (CI), 0.81–2.7;P = 0.0006;r = 0.46; n = 52] and 1.76 CD4% faster for every increase in log10 DNA copies/105 PBMC (95% CI 0.46–3.1;P = 0.01;r = 0.33; n = 42). In a multiple linear regression model, RNA load was related to CD4 decline independently of DNA load (P = 0.02). The overall mortality rate was 7.29/100 person-years. In a Cox regression model, the hazard rate increased by 2.12 for each log10 increase in RNA load (95% CI, 1.3–3.5;P = 0.0023) but only by 1.09 for each log10 increase in DNA load (95% CI, 0.64–1.87;P = 0.8). ConclusionThis longitudinal study shows for the first time that a baseline HIV-2 RNA load predicts the rate of disease progression. HIV-2-infected patients with a high viral load may need to be treated as vigorously as HIV-1 patients.

Seroprevalence of hepatitis B and C virus in HIV-1 and HIV-2 infected Gambians

BackgroundThe prevalence of HIV/hepatitis co-infection in sub-Saharan Africa is not well documented, while both HIV and HBV are endemic in this area.ObjectiveThe aim of this study is to determine the seroprevalence of HBV and HCV virus in HIV-infected subjects in the Gambia.MethodsPlasma samples from HIV infected patients (190 individuals with clinically defined AIDS and 382 individuals without AIDS) were tested retrospectively for the presence of HBV sero-markers and for serum HBV DNA, screened for HCV infection by testing for anti-HCV antibody and HCV RNA.ResultsHBsAg prevalence in HIV-positive individuals is 12.2%. HIV/HBV co-infected individuals with CD4 count of <200 cells uL-1 have a higher HBV DNA viral load than patients with higher CD4 count (log 4.0 vs. log 2.0 DNA copies/ml, p < 0.05). Males (OR = 1.8, 95% CI: 1.0, 3.2) were more likely to be HBsAg positive than female. HCV seroprevalence was 0.9% in HIV-positive individuals.ConclusionThe prevalence of HBsAg carriage in HIV- infected Gambians is similar to that obtained in the general population. However co-infected individuals with reduced CD4 levels, indicative of AIDS had higher prevalence of HBeAg retention and elevated HBV DNA levels compared to non-AIDS patients with higher CD4 count.

Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village

BackgroundThere have been no previous studies of the long-term survival and temporal changes in plasma viral load among HIV-2 infected subjects.Methods133 HIV-2 infected and 158 HIV-uninfected subjects from a rural area in North-west Guinea-Bissau, West Africa were enrolled into a prospective cohort study in 1991 and followed-up to mid-2009. Data were collected on four occasions during that period on HIV antibodies, CD4% and HIV-2 plasma viral load.ResultsMedian age (interquartile range [IQR]) of HIV-2 infected subjects at time of enrollment was 47 (36, 60) years, similar to that of HIV-uninfected control subjects, 49 (38, 62) (p = 0.4). Median (IQR) plasma viral load and CD4 percentage were 347 (50, 4,300) copies/ml and 29 (22, 35) respectively.Overall loss to follow-up to assess vital status was small, at 6.7% and 6.3% for HIV-2 infected and uninfected subjects respectively. An additional 17 (12.8%) and 16 (10.1%) of HIV-2 infected and uninfected subjects respectively were censored during follow-up due to infection with HIV-1. The mortality rate per 100 person-years (95% CI) was 4.5 (3.6, 5.8) among HIV-2 infected subjects compared to 2.1 (1.6, 2.9) among HIV-uninfected (age-sex adjusted rate ratio 1.9 (1.3, 2.8, p < 0.001) representing a 2-fold excess mortality rate associated with HIV-2 infection.Viral load measurements were available for 98%, 78%, 77% and 61% HIV-2 infected subjects who were alive and had not become super-infected with HIV-1, in 1991, 1996, 2003 and 2006 respectively. Median plasma viral load (RNA copies per ml) (IQR) did not change significantly over time, being 150 (50, 1,554; n = 77) in 1996, 203 (50, 2,837; n = 47) in 2003 and 171 (50, 497; n = 31) in 2006. Thirty seven percent of HIV-2 subjects had undetectable viraemia (<100 copies/ml) at baseline: strikingly, mortality in this group was similar to that of the general population.ConclusionsA substantial proportion of HIV-2 infected subjects in this cohort have stable plasma viral load, and those with an undetectable viral load (37%) at study entry had a normal survival rate. However, the sequential laboratory findings need to be interpreted with caution given the number of individuals who could not be re-examined.

New epidemiology of Staphylococcus aureus infection in Africa

Research on African Staphylococcus aureus has been largely neglected in the past, despite the cultural and geographical diversity in Africa, which has a significant impact on the epidemiology of this pathogen. The polarity between developed urban societies and remote rural populations (e.g. Pygmies), combined with close contact with animals (e.g. livestock and domestic animals, and wildlife), makes the epidemiology of S. aureus on the African continent unique and fascinating. Here, we try to draw an epidemiological picture of S. aureus colonization and infection in Africa, and focus on the wide spread of Panton-Valentine leukocidin-positive isolates, the emergence of the hypervirulent methicillin-resistant S. aureus (MRSA) clone USA300, and the dissemination of the typical African clone MRSA sequence type 88.

Epidemiology and population structure of Staphylococcus aureus in various population groups from a rural and semi urban area in Gabon, Central Africa

Little data is available on the epidemiology of Staphylococcus aureus in Africa. In the present study we aim at characterizing the population structure of S. aureus in healthy subjects from a rural and a semi-urban area in Lambaréné, Gabon as well as in hospital staff and inpatients. In total, 500 subjects were screened for S. aureus colonization of the nares, axillae and inguinal region. Overall, 146 (29%) were positive. We found 46 different spa types. The most frequent spa types were t084 (35%) and the agr II was the most prevalent subtype of the accessory gene regulator (56%, n=82). Five isolates (3%) were methicillin resistant S. aureus (MRSA). Carriage rates of S. aureus in Gabon are comparable to developed countries. MRSA is for the first time described and could pose a significant health threat in this region with limited access to microbiological laboratory facilities and to adequate antimicrobial agents.

Virological Response to Highly Active Antiretroviral Therapy in Patients Infected with Human Immunodeficiency Virus Type 2 (HIV-2) and in Patients Dually Infected with HIV-1 and HIV-2 in The Gambia and Emergence of Drug-Resistant Variants

ABSTRACT Drug design, antiretroviral therapy (ART), and drug resistance studies have focused almost exclusively on human immunodeficiency virus type 1 (HIV-1), resulting in limited information for patients infected with HIV-2 and for those dually infected with HIV-1 and HIV-2. In this study, 20 patients, 12 infected with HIV-2 and 8 dually infected with HIV-1 and HIV-2, all treated with zidovudine (ZDV), lamivudine (3TC), and lopinavir-ritonavir (LPV/r), were followed up longitudinally for about 3 years. For 19/20 patients, viral loads were reduced to undetectable levels; the patient whose viral load remained detectable reported adverse effects associated with LPV/r that had caused him to stop taking all the drugs. HIV-2 strains containing mutations in both the protease and the reverse transcriptase gene that may confer drug resistance were observed in two patients with viral rebound, as early as 130 days (4.3 months) after the initiation of therapy. We conclude that the combination of ZDV, 3TC, and LPV/r is able to provide efficient and durable suppression of HIV-1 and HIV-2 for as long as 3 years in HIV-2-infected and dually infected patients. However, the emergence of HIV-1 and HIV-2 strains containing drug-resistant mutations can compromise the efficacy of this highly active ART.