tat Exon 1 Exhibits Functional Diversity during HIV-1 Subtype C Primary Infection

Human immunodeficiency virus type 1 (HIV-1) Tat is a mediator of viral transcription and is involved in the control of virus replication. However, associations between HIV-1 Tat diversity and functional effects during primary HIV-1 infection are still unclear. We estimated selection pressures in tat exon 1 using the mixed-effects model of evolution with 672 viral sequences generated from 20 patients infected with HIV-1 subtype C (HIV-1C) over 500 days postseroconversion. tat exon 1 residues 3, 4, 21, 24, 29, 39, and 68 were under positive selection, and we established that specific amino acid signature patterns were apparent in primary HIV-1C infection compared with chronic infection. We assessed the impact of these mutations on long terminal repeat (LTR) activity and found that Tat activity was negatively affected by the Ala21 substitution identified in 13/20 (65%) of patients, which reduced LTR activity by 88% (±1%) (P < 0.001). The greatest increase in Tat activity was seen with the Gln35/Lys39 double mutant that resulted in an additional 49% (±14%) production of LTR-driven luciferase (P = 0.012). There was a moderate positive correlation between Tat-mediated LTR activity and HIV-1 RNA in plasma (P = 0.026; r = 0.400) after 180 days postseroconversion that was reduced by 500 days postseroconversion (P = 0.043; r = 0.266). Although Tat activation of the LTR is not a strong predictor of these clinical variables, there are significant linear relationships between Tat transactivation and patients' plasma viral loads and CD4 counts, highlighting the complex interplay between Tat mutations in early HIV-1C infection

Antimicrobial susceptibility of staphylococci species from cow foremilk originating from dairy farms around Gaborone, Botswan

Objective: To determine the prevalence of antibiotic susceptibility of Staphylococcus species isolated from foremilk samples. Setting: Milk was collected from five farms within a 70 km radius of Gaborone, Botswana. Subjects: Two hundred and twenty five staphylococci isolates from foremilk samples. Main outcome measures: Antibiotic susceptibility tests to penicillin G, ampicillin, tetracycline, erythromycin, cephalothin, chloramphenicol, methicillin, gentamicin and vancomycin. Results: The susceptibility patterns of the staphylococcal strains to the antibiotics were as follows: penicillin G (47.1%), ampicillin (58.7%), tetracycline (62.7%), erythromycin (72%), cephalothin (72.9%), chloramphenicol (79.1%), methicillin (86.2%), gentamicin (88.9%) and vancomycin (100%). Lower susceptibility to chloramphenicol, ethicillin and gentamicin was displayed by Staphylococcus epidermidis, S. haemolyticus and S. saprophyticus. Only 19 (8.5%) of the isolates were susceptible to all the antibiotics tested. The most common multiple resistance patterns encountered were penicillin-ampicillin (9.3%), penicillin-erythromycinampicillin (6.1%) and erythromycin-tetracycline - ampicillin (3.6%). Conclusion: Most of the Staphylococcus isolates were resistant to one or more of the antimicrobial agents, with none being resistant to vancomycin. Inappropriate use of antibiotics is suspected to be a major contributory factor in the relatively high level of resistance to antimicrobial agents observed in this study. Therefore, milk can act as a very good source of antibiotic resistant Staphylococcus species posing a threat to consumers. (East African Medical Journal: 2002 79(1): 45-48

Slow CD4+ T-Cell Recovery in Human Immunodeficiency Virus/Hepatitis B Virus-Coinfected Patients Initiating Truvada-Based Combination Antiretroviral Therapy in Botswana

Background. Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection has emerged as an important cause of morbidity and mortality. We determined the response to Truvada-based first-line combination antiretroviral therapy (cART) in HIV/HBV-coinfected verus HIV-monoinfected patients in Botswana. Methods. Hepatitis B virus surface antigen (HBsAg), HBV e antigen (HBeAg), and HBV deoxyribonucleic acid (DNA) load were determined from baseline and follow-up visits in a longitudinal cART cohort of Truvada-based regimen. We assessed predictors of HBV serostatus and viral suppression (undetectable HBV DNA) using logistic regression techniques. Results. Of 300 participants, 28 were HBsAg positive, giving an HIV/HBV prevalence of 9.3% (95% confidence interval [CI], 6.3–13.2), and 5 of these, 17.9% (95% CI, 6.1–36.9), were HBeAg positive. There was a reduced CD4+ T-cell gain in HIV/HBV-coinfected compared with HIV-monoinfected patients. Hepatitis B virus surface antigen and HBeAg loss was 38% and 60%, respectively, at 24 months post-cART initiation. The HBV DNA suppression rates increased with time on cART from 54% to 75% in 6 and 24 months, respectively. Conclusions. Human immunodeficiency virus/HBV coinfection negatively affected immunologic recovery compared with HIV-1C monoinfection. Hepatitis B virus screening before cART initiation could help improve HBV/HIV treatment outcomes and help determine treatment options when there is a need to switch regimens