Browsing by Subject "HIV infections"
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- ItemOpen AccessAnaemia in acute HIV-1 subtype C infection(Public Library of Science, 2008) Mlisana, Koleka; Auld, Sara C; Grobler, Anneke; Loggerenberg, Francois van; Williamson, Carolyn; Iriogbe, Itua; Sobieszczyk, Magdalena E; Karim, Salim S Abdool; Team, for the CAPRISA Acute Infection StudyBACKGROUND: The high prevalence of anaemia and the increased morbidity and mortality associated with anaemia during AIDS has been well described yet there has been little information about anaemia and changes in haemoglobin levels during acute and early HIV-1 infection. METHODS: HIV-negative women (n = 245) were enrolled into an observational cohort as part of the Centre for the AIDS Programme of Research in South Africa (CAPRISA) Acute Infection Study. Acute infection was diagnosed following a positive HIV RNA PCR in the absence of antibodies, or detection of HIV-1 antibodies within 3 months of a previously negative antibody test. Haemotologic parameters were assessed before infection and at regular intervals in the first twelve months of HIV infection. RESULTS: Fifty-seven participants with acute HIV infection were identified at a median of 14.5 days post-infection (range 10-81) and were enrolled in the CAPRISA Acute Infection cohort at a median of 41 days post-infection (range 15-104). Mean haemoglobin prior to HIV-1 infection was 12.7 g/dL, with a mean decline of 0.46 g/dL following infection. The prevalence of anaemia increased from 25.0% prior to HIV-1 infection to 52.6% at 3 months post-infection, 61.1% at 6 months post-infection, and 51.4% at 12 months post-infection. CONCLUSIONS: Haematologic derangements and anaemia with a trend towards iron deficiency are common with acute HIV-1 subtype C infection in this small cohort. The negative impact of anaemia concurrent with established HIV infection upon morbidity and mortality has been well documented but the prognostic potential and long-term effects of anaemia during acute HIV-1 infection remain unknown.
- ItemOpen AccessAnti-retroviral therapy increases the prevalence of dyslipidemia in South African HIV-infected patients(Public Library of Science, 2016) Dave, Joel A; Levitt, Naomi S; Ross, Ian L; Lacerda, Miguel; Maartens, Gary; Blom, DirkPurpose Data on the prevalence of dyslipidaemia and associated risk factors in HIV-infected patients from sub-Saharan Africa is sparse. We performed a cross-sectional analysis in a cohort of HIV-infected South African adults. METHODS: We studied HIV-infected patients who were either antiretroviral therapy (ART)-naive or receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based or protease inhibitor (PI)-based ART. Evaluation included fasting lipograms, oral glucose tolerance tests and clinical anthropometry. Dyslipidemia was defined using the NCEP ATPIII guidelines. RESULTS: The median age of the participants was 34 years (range 19-68 years) and 78% were women. The prevalence of dyslipidemia in 406 ART-naive and 551 participants on ART was 90.0% and 85%, respectively. Low HDL-cholesterol (HDLC) was the most common abnormality [290/406 (71%) ART-naïve and 237/551 (43%) ART- participants]. Participants on ART had higher triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDLC) and HDLC than the ART-naïve group. Severe dyslipidaemia, (LDLC> 4.9 mmol/L or TG >5.0 mmol/L) was present in <5% of participants. In multivariate analyses there were complex associations between age, gender, type and duration of ART and body composition and LDLC, HDLC and TG, which differed between ART-naïve and ART-participants. CONCLUSION: Participants on ART had higher TG, TC, LDLC and HDLC than those who were ART-naïve but severe lipid abnormalities requiring evaluation and treatment were uncommon.
- ItemOpen AccessAntiretroviral therapy, especially Efavirenz, is associated with low bone mineral density in HIV-infected South Africans(Public Library of Science, 2015) Dave, Joel A; Cohen, Karen; Micklesfield, Lisa K; Maartens, Gary; Levitt, Naomi SPurpose We determined the prevalence and correlates of low bone mineral density (BMD) in HIV-infected South Africans as there is a paucity of such data from Africa. METHODS: BMD and serum 25-hydroxyvitamin D were measured in HIV-positive participants on antiretroviral therapy (ART) and in those not yet on ART (ART-naïve). RESULTS: We enrolled 444 participants [median age 35(IQR: 30, 40) years; 77% women]. BMD was low (z score <-2SD) in 17% and 5% of participants at the lumbar spine and total hip, respectively. Total hip [0.909 (SD 0.123) vs 0.956 (SD 0.124) g/cm 2 , p = 0.0001] and neck of femur BMD [0.796 (SD 0.130) vs 0.844 (SD 0.120) g/cm 2 , p = 0.0001] were lower in the ART, compared to the ART-naïve group. Vitamin D deficiency was present in 15% of participants and was associated with efavirenz use [adjusted OR 2.04 (95% CI 1.01 to 4.13)]. In a multivariate linear regression, exposure to efavirenz or lopinavir-based ART was associated with lower total hip BMD, whereas higher weight, being male and higher vitamin D concentration were associated with higher total hip BMD (adjusted R 2 = 0.28). Age, weight, sex, and the use of efavirenz-based ART were independently associated with lumbar spine BMD (adjusted R 2 = 0.13). CONCLUSIONS: Vitamin D status, use of efavirenz or lopinavir/ritonavir, weight, age and sex are significantly associated with lower BMD in this young cohort of HIV-infected South Africans.
- ItemOpen AccessCCR2-V64I polymorphism is associated with increased risk of cervical cancer but not with HPV infection or pre-cancerous lesions in African women(BioMed Central Ltd, 2010) Chatterjee, Koushik; Dandara, Collet; Hoffman, Margaret; Williamson, Anna-LiseBACKGROUND: Cervical cancer, caused by specific oncogenic types of human papillomavirus (HPV), is the second most common cancer in women worldwide. A large number of young sexually active women get infected by HPV but only a small fraction of them have persistent infection and develop cervical cancer pointing to co- factors including host genetics that might play a role in outcome of the HPV infection. This study investigated the role of CCR2-V64I polymorphism in cervical cancer, pre-cancers and HPV infection in South African women resident in Western Cape. CCR2-V64I polymorphism has been previously reported to influence the progression to cervical cancer in some populations and has also been associated with decreased progression from HIV infection to AIDS. METHODS: Genotyping for CCR2-V64I was done by PCR-SSP in a case-control study of 446 women (106 black African and 340 mixed-ancestry) with histologically confirmed invasive cervical cancer and 1432 controls (322 black African and 1110 mixed-ancestry) group-matched (1:3) by age, ethnicity and domicile status. In the control women HPV was detected using the Digene Hybrid Capture II test and cervical disease was detected by cervical cytology. RESULTS: The CCR2-64I variant was significantly associated with cervical cancer when cases were compared to the control group (P = 0.001). Further analysis comparing selected groups within the controls showed that individuals with abnormal cytology and high grade squamous intraepitleial neoplasia (HSIL) did not have this association when compared to women with normal cytology. HPV infection also showed no association with CCR2-64I variant. Comparing SIL positive controls with the cases showed a significant association of CCR2-64I variant (P = 0.001) with cervical cancer. CONCLUSIONS: This is the first study of the role of CCR2-V64I polymorphism in cervical cancer in an African population. Our results show that CCR2-64I variant is associated with the risk of cervical cancer but does not affect the susceptibility to HPV infection or HSIL in South African women of black and mixed-ancestry origin. This result implies that the role of CCR2 is important in invasive cancer of the cervix but not in HPV infection or in the development of pre-cancers.
- ItemOpen AccessChallenges of diagnosing acute HIV-1 subtype C infection in African women: performance of a clinical algorithm and the need for point-of-care nucleic-acid based testing(Public Library of Science, 2013) Mlisana, Koleka; Sobieszczyk, Magdalena; Werner, Lise; Feinstein, Addi; van Loggerenberg, Francois; Naicker, Nivashnee; Williamson, Carolyn; Garrett, NigelBACKGROUND: Prompt diagnosis of acute HIV infection (AHI) benefits the individual and provides opportunities for public health intervention. The aim of this study was to describe most common signs and symptoms of AHI, correlate these with early disease progression and develop a clinical algorithm to identify acute HIV cases in resource limited setting. METHODS: 245 South African women at high-risk of HIV-1 were assessed for AHI and received monthly HIV-1 antibody and RNA testing. Signs and symptoms at first HIV-positive visit were compared to HIV-negative visits. Logistic regression identified clinical predictors of AHI. A model-based score was assigned to each predictor to create a risk score for every woman. RESULTS: Twenty-eight women seroconverted after a total of 390 person-years of follow-up with an HIV incidence of 7.2/100 person-years (95%CI 4.5-9.8). Fifty-seven percent reported ≥1 sign or symptom at the AHI visit. Factors predictive of AHI included age <25 years (OR = 3.2; 1.4-7.1), rash (OR = 6.1; 2.4-15.4), sore throat (OR = 2.7; 1.0-7.6), weight loss (OR = 4.4; 1.5-13.4), genital ulcers (OR = 8.0; 1.6-39.5) and vaginal discharge (OR = 5.4; 1.6-18.4). A risk score of 2 correctly predicted AHI in 50.0% of cases. The number of signs and symptoms correlated with higher HIV-1 RNA at diagnosis (r = 0.63; p<0.001). CONCLUSIONS: Accurate recognition of signs and symptoms of AHI is critical for early diagnosis of HIV infection. Our algorithm may assist in risk-stratifying individuals for AHI, especially in resource-limited settings where there is no routine testing for AHI. Independent validation of the algorithm on another cohort is needed to assess its utility further. Point-of-care antigen or viral load technology is required, however, to detect asymptomatic, antibody negative cases enabling early interventions and prevention of transmission.
- ItemOpen AccessCombination HIV prevention among MSM in South Africa: results from agent-based modeling(Public Library of Science, 2014) Brookmeyer, Ron; Boren, David; Baral, Stefan D; Bekker, Linda- Gail; Phaswana-Mafuya, Nancy; Beyrer, Chris; Sullivan, Patrick SHIV prevention trials have demonstrated the effectiveness of a number of behavioral and biomedical interventions. HIV prevention packages are combinations of interventions and offer potential to significantly increase the effectiveness of any single intervention. Estimates of the effectiveness of prevention packages are important for guiding the development of prevention strategies and for characterizing effect sizes before embarking on large scale trials. Unfortunately, most research to date has focused on testing single interventions rather than HIV prevention packages. Here we report the results from agent-based modeling of the effectiveness of HIV prevention packages for men who have sex with men (MSM) in South Africa. We consider packages consisting of four components: antiretroviral therapy for HIV infected persons with CD4 count <350; PrEP for high risk uninfected persons; behavioral interventions to reduce rates of unprotected anal intercourse (UAI); and campaigns to increase HIV testing. We considered 163 HIV prevention packages corresponding to different intensity levels of the four components. We performed 2252 simulation runs of our agent-based model to evaluate those packages. We found that a four component package consisting of a 15% reduction in the rate of UAI, 50% PrEP coverage of high risk uninfected persons, 50% reduction in persons who never test for HIV, and 50% ART coverage over and above persons already receiving ART at baseline, could prevent 33.9% of infections over 5 years (95% confidence interval, 31.5, 36.3). The package components with the largest incremental prevention effects were UAI reduction and PrEP coverage. The impact of increased HIV testing was magnified in the presence of PrEP. We find that HIV prevention packages that include both behavioral and biomedical components can in combination prevent significant numbers of infections with levels of coverage, acceptance and adherence that are potentially achievable among MSM in South Africa.
- ItemOpen AccessComparison of mantoux and tine tuberculin skin tests in BCG-vaccinated children investigated for tuberculosis(Public Library of Science, 2009) Pan, Wenli; Matizirofa, Lyness; Workman, Lesley; Hawkridge, Tony; Hanekom, Willem; Mahomed, Hassan; Hussey, Gregory; Hatherill, MarkBackground: Tuberculin skin tests (TSTs) are long-established screening methods for tuberculosis (TB). We aimed to compare agreement between the intradermal Mantoux and multipuncture percutaneous Tine methods and to quantify risk factors for a positive test result. Methodology/Principal Findings: 1512 South African children younger than 5 years of age who were investigated for tuberculosis (TB) during a Bacille Calmette Guerin (BCG) trial were included in this analysis. Children underwent both Mantoux and Tine tests. A positive test was defined as Mantoux ≥15 mm or Tine ≥ Grade 3 for the binary comparison. Agreement was evaluated using kappa (binary) and weighted kappa (hierarchical). Multivariate regression models identified independent risk factors for TST positivity. The Mantoux test was positive in 430 children (28.4%) and the Tine test in 496 children (32.8%, p<0.0001), with observed binary agreement 87.3% (kappa 0.70) and hierarchical agreement 85.0% (weighted kappa 0.66). Among 173 children culture-positive for Mycobacterium tuberculosis, Mantoux was positive in 49.1% and Tine in 54.9%, p<0.0001 (kappa 0.70). Evidence of digit preference was noted for Mantoux readings at 5 mm threshold intervals. After adjustment for confounders, a positive culture, suggestive chest radiograph, and proximity of TB contact were risk factors for a positive test using both TST methods. There were no independent associations between ethnicity, gender, age, or over-crowding, and TST result. Conclusions/Significance: The Tine test demonstrated a higher positive test rate than the Mantoux, with substantial agreement between TST methods among young BCG-vaccinated children. TB disease and exposure factors, but not demographic variables, were independent risk factors for a positive result using either test method. These findings suggest that the Tine might be a useful screening tool for childhood TB in resource-limited countries.
- ItemOpen AccessCorneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control study(Public Library of Science, 2013) Pathai, Sophia; Lawn, Stephen D; Shiels, Paul G; Weiss, Helen A; Cook, Colin; Wood, Robin; Gilbert, Clare EBACKGROUND: Cellular senescence may be a key factor in HIV-related premature biological aging. We assessed features of the corneal endothelium that are known to be associated with biological aging, and cellular senescence markers in HIV-infected adults. METHODS: Case-control study of 242 HIV-infected adults and 249 matched controls. Using specular microscopy, the corneal endothelium was assessed for features of aging (low endothelial cell density [ECD], high variation in cell size, and low hexagonality index). Data were analysed by multivariable regression. CDKN2A expression (a cell senescence mediator) was measured in peripheral blood leukocytes and 8-hydroxy-2′-deoxyguanosine (8-OHDG; an oxidative DNA damage marker) levels were measured in plasma. RESULTS: The median age of both groups was 40 years. Among HIV-infected adults, 88% were receiving antiretroviral therapy (ART); their median CD4 count was 468 cells/µL. HIV infection was associated with increased odds of variation in cell size (OR = 1.67; 95% CI: 1.00-2.78, p = 0.04). Among HIV-infected participants, low ECD was independently associated with current CD4 count <200 cells/µL (OR = 2.77; 95%CI: 1.12-6.81, p = 0.03). In participants on ART with undetectable viral load, CDKN2A expression and 8-OHDG levels were higher in those with accelerated aging, as reflected by lower ECD. CONCLUSIONS: The corneal endothelium shows features consistent with HIV-related accelerated senescence, especially among those with poor immune recovery.
- ItemOpen AccessCost-effectiveness of highly active antiretroviral therapy in South Africa(Public Library of Science, 2005) Badri, Motasim; Maartens, Gary; Mandalia, Sundhiya; Bekker, Linda-Gail; Penrod, John R; Platt, Robert W; Wood, Robin; Beck, Eduard JHealthcare costs for HIV-infected South African adults on HAART compared with costs for HIV-infected controls not on HAART. Authors conclude HAART is cost effective.
- ItemOpen AccessCreating an African HIV clinical research and prevention trials network: HIV prevalence, incidence and transmission(Public Library of Science, 2015) Kamali, Anatoli; Price, Matt A; Lakhi, Shabir; Karita, Etienne; Inambao, Mubiana; Sanders, Eduard J; Anzala, Omu; Latka, Mary H; Bekker, Linda-Gail; Kaleebu, PontianoHIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner.
- ItemOpen AccessA descriptive analysis of HIV prevalence, HIV service uptake, and HIV-related risk behaviour among patients attending a mental health clinic in Rural Malawi(Public Library of Science, 2013) Lommerse, Kinke; Stewart, Robert C; Chilimba, Queen; Akker, Thomas van den; Lund, CrickBACKGROUND: Human immunodeficiency virus (HIV) and mental illness are interlinked health problems; mental illness may pose a risk for contracting HIV and HIV-positive individuals are at higher risk of mental illness. However, in countries with high HIV prevalence, the main focus of HIV-related health programmes is usually on prevention and treatment of somatic complications of HIV, and mental illness is not given high priority. We examined HIV prevalence, uptake of HIV services, and HIV-related risk behaviour among people attending a mental health clinic in rural Malawi. METHODOLOGY: Semi-structured interviews were performed with patients capable to consent (94%), and with those accompanied by a capable caregiver who consented. HIV counselling and testing was offered to participants. FINDINGS: Among 174 participants, we collected 162 HIV test results (91%). HIV prevalence was 14.8%. Women were three times as likely to be HIV-positive compared to men. Two-thirds of participants reported having been tested for HIV prior to this study. The uptake of HIV-services among HIV-positive patients was low: 35% did not use recommended prophylactic therapy and 44% of patients not receiving antiretroviral treatment (ART) had never been assessed for ART eligibility. The reported rate of sexual activity was 61%, and 9% of sexually active participants had multiple partners. Inconsistent condom use with stable (89%) and occasional (79%) sexual partners, and absence of knowledge of the HIV status of those partners (53%, 63%) indicate high levels of sexual risk behaviour. CONCLUSIONS: HIV-prevalence among persons attending the clinic, particularly men, was lower than among the general population in a population survey. The rate of HIV testing was high, but there was low uptake of preventive measures and ART. This illustrates that HIV-positive individuals with mental illness or epilepsy constitute a vulnerable population. HIV programmes should include those with neuropsychiatric illness.
- ItemOpen AccessDevelopment of a simple reliable radiographic scoring system to aid the diagnosis of pulmonary tuberculosis(Public Library of Science, 2013) Pinto, Lancelot M; Dheda, Keertan; Theron, Grant; Allwood, Brian; Calligaro, Gregory; van Zyl-Smit, Richard; Peter, Jonathan; Schwartzman, Kevin; Menzies, Dick; Bateman, Eric; Pai, Madhukar; Dawson, RodneyRationale: Chest radiography is sometimes the only method available for investigating patients with possible pulmonary tuberculosis (PTB) with negative sputum smears. However, interpretation of chest radiographs in this context lacks specificity for PTB, is subjective and is neither standardized nor reproducible. Efforts to improve the interpretation of chest radiography are warranted. Objectives To develop a scoring system to aid the diagnosis of PTB, using features recorded with the Chest Radiograph Reading and Recording System (CRRS). METHODS: Chest radiographs of outpatients with possible PTB, recruited over 3 years at clinics in South Africa were read by two independent readers using the CRRS method. Multivariate analysis was used to identify features significantly associated with culture-positive PTB. These were weighted and used to generate a score. RESULTS: 473 patients were included in the analysis. Large upper lobe opacities, cavities, unilateral pleural effusion and adenopathy were significantly associated with PTB, had high inter-reader reliability, and received 2, 2, 1 and 2 points, respectively in the final score. Using a cut-off of 2, scores below this threshold had a high negative predictive value (91.5%, 95%CI 87.1,94.7), but low positive predictive value (49.4%, 95%CI 42.9,55.9). Among the 382 TB suspects with negative sputum smears, 229 patients had scores <2; the score correctly ruled out active PTB in 214 of these patients (NPV 93.4%; 95%CI 89.4,96.3). The score had a suboptimal negative predictive value in HIV-infected patients (NPV 86.4, 95% CI 75,94). CONCLUSIONS: The proposed scoring system is simple, and reliably ruled out active PTB in smear-negative HIV-uninfected patients, thus potentially reducing the need for further tests in high burden settings. Validation studies are now required.
- ItemOpen AccessEarly and late direct costs in a Southern African antiretroviral treatment programme: a retrospective cohort analysis(Public Library of Science, 2009) Leisegang, Rory; Cleary, Susan; Hislop, Michael; Davidse, Alistair; Regensberg, Leon; Little, Francesca; Maartens, GaryGary Maartens and colleagues describe the direct heath care costs and identify the drivers of cost over time in an HIV managed care program in Southern Africa.
- ItemOpen AccessEarly mortality during initial treatment of tuberculosis in patients co-infected with HIV at the Yaoundé Central Hospital, Cameroon : an 8-year retrospective cohort study (2006-2013)(Public Library of Science, 2015) Bigna, Jean Joel R; Noubiap, Jean Jacques N; Agbor, Ako A; Plottel, Claudia S; Billong, Serge Clotaire; Ayong, André Patrick R; Koulla-Shiro, SinataBACKGROUND: Understanding contributors to mortality during the initial phase of tuberculosis (TB) treatment in patients co-infected with HIV would guide targeted interventions to improve survival. The aim of this study was to ascertain the incidence of death during the initial 2 months (new cases) and 3 months (retreatment cases) of TB treatment and to assess correlates of mortality in HIV co-infected patients. METHODS: We conducted a hospital-based retrospective cohort study from January 2006 to December 2013 at Yaoundé Central Hospital, Cameroon. We reviewed medical records to identify co-infected TB/HIV inpatients aged 15 years and older who died during TB treatment. Death was defined as any death occurring during TB treatment, as per World Health Organization recommendations. We collected socio-demographic, clinical and laboratory data. We conducted multivariable logistic binary regression analysis to identify factors associated with death during the intensive phase of TB treatment. Magnitudes of associations were expressed by adjusted odds ratio (a OR ) with 95% confidence interval. A p value < 0.05 was considered statistically significant. RESULTS: The 99 patients enrolled had a mean age of 39.5 (standard deviation 10.9) years and 53% were male. Patients were followed for 276.3 person-months of observation (PMO). Forty nine patients were died during intensive phase of TB treatment. Death incidence during the intensive phase of TB treatment was 32.2 per 100 PMO. Having a non-AIDS comorbidity (a OR 2.47, 95%CI 1.22-5.02, p = 0.012), having extra-pulmonary TB (a OR 1.89, 95%CI 1.05-3.43, p = 0.035), and one year increase in duration of known HIV infection (aOR 1.23, 95%CI 1.004-1.49) were independently associated with death during the intensive phase of TB treatment. CONCLUSIONS: Mortality incidence during intensive phase of TB treatment was high among TB/HIV co-infected patients during TB treatment; and strongly associated with extra pulmonary TB suggesting advanced stage of immunosuppression and non-AIDS comorbidities. Early HIV diagnosis and care and good management of non-comorbidities can reduce this incidence.
- ItemOpen AccessEffect of female genital schistosomiasis and anti-schistosomal treatment on monocytes, CD4+ T-cells and CCR5 expression in the female genital tract(Public Library of Science, 2014) Kleppa, Elisabeth; Ramsuran, Veron; Zulu, Siphosenkosi; Karlsen, Gunn Hege; Bere, Alfred; Passmore, Jo-Ann S; Ndhlovu, Patricia; Lillebø, Kristine; Holmen, Sigve D; Onsrud, MathiasBACKGROUND: Schistosoma haematobium is a waterborne parasite that may cause female genital schistosomiasis (FGS), characterized by genital mucosal lesions. There is clinical and epidemiological evidence for a relationship between FGS and HIV. We investigated the impact of FGS on HIV target cell density and expression of the HIV co-receptor CCR5 in blood and cervical cytobrush samples. Furthermore we evaluated the effect of anti-schistosomal treatment on these cell populations. Design The study followed a case-control design with post treatment follow-up, nested in an on-going field study on FGS. METHODS: Blood and cervical cytobrush samples were collected from FGS negative and positive women for flow cytometry analyses. Urine samples were investigated for schistosome ova by microscopy and polymerase chain reaction (PCR). RESULTS: FGS was associated with a higher frequency of CD14 + cells (monocytes) in blood (11.5% in FGS+ vs. 2.2% in FGS-, p = 0.042). Frequencies of CD4 + cells expressing CCR5 were higher in blood samples from FGS+ than from FGS- women (4.7% vs. 1.5%, p = 0.018). The CD14 + cell population decreased significantly in both compartments after anti-schistosomal treatment (p = 0.043). Although the frequency of CD4+ cells did not change after treatment, frequencies of CCR5 expression by CD4+ cells decreased significantly in both compartments (from 3.4% to 0.5% in blood, p = 0.036; and from 42.4% to 5.6% in genital samples, p = 0.025). CONCLUSIONS: The results support the hypothesis that FGS may increase the risk of HIV acquisition, not only through damage of the mucosal epithelial barrier, but also by affecting HIV target cell populations, and that anti-schistosomal treatment can modify this.
- ItemOpen AccessEffect of standard tuberculosis treatment on plasma cytokine levels in patients with active pulmonary tuberculosis(Public Library of Science, 2012) Riou, Catherine; Peixoto, Blas Perez; Roberts, Lindi; Ronacher, Katharina; Walzl, Gerhard; Manca, Claudia; Rustomjee, Roxana; Mthiyane, Thuli; Fallows, Dorothy; Gray, Clive MBACKGROUND: Sputum Mycobacterium tuberculosis (Mtb) culture is commonly used to assess response to antibiotic treatment in individuals with pulmonary tuberculosis (TB). Such techniques are constrained by the slow growth rate of Mtb, and more sensitive methods to monitor Mtb clearance are needed. The goal of this study was to evaluate changes in plasma cytokines in patients undergoing treatment for TB as a means of identifying candidate host markers associated with microbiologic response to therapy. METHODS: Twenty-four plasma cytokines/chemokines were measured in 42 individuals diagnosed with active pulmonary TB, 52% were HIV co-infected. Individuals, undergoing a 26-week standard TB treatment, were followed longitudinally over 18 months and measurements were associated with HIV status and rates of sputum culture conversion. RESULTS: Plasma concentrations of interferon-inducible protein-10 (IP-10) and vascular endothelial growth factor (VEGF) were significantly reduced upon TB treatment, regardless of HIV status. By the end of treatment, IP-10 concentrations were significantly lower in HIV negative individuals when compared to HIV-positive individuals (p = 0.02). Moreover, in HIV negative patients, plasma VEGF concentrations, measured as early as 2-weeks post TB treatment initiation, positively correlated with the time of sputum conversion (p = 0.0017). No significant changes were observed in other studied immune mediators. CONCLUSIONS: These data suggest that VEGF plasma concentration, measured during early TB treatment, could represent a surrogate marker to monitor sputum culture conversion in HIV uninfected individuals.
- ItemOpen AccessEffectiveness of the first district-wide programme for the prevention of mother-to-child transmission of HIV in South Africa(2005) Coetzee, David; Hilderbrand, Katherine; Boulle, Andrew; Draper, Beverley; Abdullah, Fareed; Goemaere, EricObjective: The aim of this study was to estimate the field efficacy of the first routine programme for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) initiated in South Africa, in the subdistrict of Khayelitsha. Methods: A consecutive sample of 658 mother–infant pairs, identified from the PMTCT register from 1 March to 30 November 2003, were identified for enrolment in this study. Details of the regimen received were established and HIV status of the infants at between 6 and 10 weeks of age was determined by qualitative DNA polymerase chain reaction. Zidovudine (AZT) was provided antenatally from week 34 of gestation and during labour. Infant formula milk was offered to mothers who chose not to breastfeed. The protocol was amended in July 2003 such that women who had received < 2 weeks of treatment with AZT were given a single dose of nevirapine (NVP) at the onset of labour, and the infant received a weight-adjusted dose of NVP within 72 h of delivery. Results: Of the 535 mother–infant pairs (81%) eventually included in the study, 410 (77%) received an effective PMTCT intervention according to the protocol. The rate of transmission of HIV from mother to child was 8.8% (95% confidence interval (CI), 6.2–10.9). A maternal age of > 25 years was the only significant independent risk factor for transmission (odds ratio, 2.12; 95% CI, 1.14–4.07). Conclusion: The results of this study demonstrate the feasibility and effectiveness of a large-scale PMTCT programme in an urban public-sector setting.
- ItemOpen AccessEpidemic levels of drug resistant tuberculosis (MDR and XDR-TB) in a high HIV prevalence setting in Khayelitsha, South Africa(Public Library of Science, 2010) Cox, Helen S; McDermid, Cheryl; Azevedo, Virginia; Muller, Odelia; Coetzee, David; Simpson, John; Barnard, Marinus; Coetzee, Gerrit; van Cutsem, Gilles; Goemaere, EricBACKGROUND: Although multidrug-resistant tuberculosis (MDR-TB) is emerging as a significant threat to tuberculosis control in high HIV prevalence countries such as South Africa, limited data is available on the burden of drug resistant tuberculosis and any association with HIV in such settings. We conducted a community-based representative survey to assess the MDR-TB burden in Khayelitsha, an urban township in South Africa with high HIV and TB prevalence. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional survey was conducted among adult clinic attendees suspected for pulmonary tuberculosis in two large primary care clinics, together constituting 50% of the tuberculosis burden in Khayelitsha. Drug susceptibility testing (DST) for isoniazid and rifampicin was conducted using a line probe assay on positive sputum cultures, and with culture-based DST for first and second-line drugs. Between May and November 2008, culture positive pulmonary tuberculosis was diagnosed in 271 new and 264 previously treated tuberculosis suspects (sample enriched with previously treated cases). Among those with known HIV status, 55% and 71% were HIV infected respectively. MDR-TB was diagnosed in 3.3% and 7.7% of new and previously treated cases. These figures equate to an estimated case notification rate for MDR-TB of 51/100,000/year, with new cases constituting 55% of the estimated MDR-TB burden. HIV infection was not significantly associated with rifampicin resistance in multivariate analyses. Conclusions/Significance There is an extremely high burden of MDR-TB in this setting, most likely representing ongoing transmission. These data highlight the need to diagnose drug resistance among all TB cases, and for innovative models of case detection and treatment for MDR-TB, in order to interrupt transmission and control this emerging epidemic.
- ItemOpen AccessEstablishing a cohort at high risk of HIV infection in South Africa: challenges and experiences of the CAPRISA 002 acute infection study(Public Library of Science, 2008) van Loggerenberg, Francois; Mlisana, Koleka; Williamson, Carolyn; Auld, Sara C; Morris, Lynn; Gray, Clive M; Karim, Quarraisha Abdool; Grobler, Anneke; Barnabas, Nomampondo; Iriogbe, ItuaObjectives To describe the baseline demographic data, clinical characteristics and HIV-incidence rates of a cohort at high risk for HIV infection in South Africa as well as the challenges experienced in establishing and maintaining the cohort. Methodology/Principle FINDINGS: Between August 2004 and May 2005 a cohort of HIV-uninfected women was established for the CAPRISA 002 Acute Infection Study, a natural history study of HIV-1 subtype C infection. Volunteers were identified through peer-outreach. The cohort was followed monthly to determine HIV infection rates and clinical presentation of early HIV infection. Risk reduction counselling and male and female condoms were provided. After screening 775 individuals, a cohort of 245 uninfected high-risk women was established. HIV-prevalence at screening was 59.6% (95% CI: 55.9% to 62.8%) posing a challenge in accruing HIV-uninfected women. The majority of women (78.8%) were self-identified as sex-workers with a median of 2 clients per day. Most women (95%) reported more than one casual sexual partner in the previous 3 months (excluding clients) and 58.8% reported condom use in their last sexual encounter. Based on laboratory testing, 62.0% had a sexually transmitted infection at baseline. During 390 person-years of follow-up, 28 infections occurred yielding seroincidence rate of 7.2 (95% CI: 4.5 to 9.8) per 100 person-years. Despite the high mobility of this sex worker cohort retention rate after 2 years was 86.1%. High co-morbidity created challenges for ancillary care provision, both in terms of human and financial resources. Conclusions/Significance Challenges experienced were high baseline HIV-prevalence, lower than anticipated HIV-incidence and difficulties retaining participants. Despite challenges, we have successfully accrued this cohort of HIV-uninfected women with favourable retention, enabling us to study the natural history of HIV-1 during acute HIV-infection. Our experiences provide lessons for others establishing similar cohorts, which will be key for advancing the vaccine and prevention research agenda in resource-constrained settings.
- ItemOpen AccessForced sexual experiences as risk factor for self-reported HIV infection among southern African lesbian and bisexual women(Public Library of Science, 2013) Sandfort, Theo G M; Baumann, Linda R M; Matebeni, Zethu; Reddy, Vasu; Southey-Swartz, IanEven though women who have sex with women are usually understood to be at no or very low risk for HIV infection, we explored whether lesbian and bisexual women in a geographical area with high HIV prevalence (Southern Africa) get tested for HIV and whether, among those women who get tested, there are women who live with HIV/AIDS. The study was conducted in collaboration with community-based organizations in Botswana, Namibia, South Africa and Zimbabwe. Data were collected via written surveys of women who in the preceding year had had sex with a woman (18 years and older; N = 591). Most participating women identified as lesbian and black. Almost half of the women (47.2%) reported ever having had consensual heterosexual sex. Engagement in transactional sex (lifetime) was reported by 18.6% of all women. Forced sex by men or women was reported by 31.1% of all women. A large proportion of the women reported to ever have been tested for HIV (78.3%); number of lifetime female and male partners was independently associated with having been tested; women who had engaged in transactional sex with women only or with women and men were less likely to have been tested. Self-reported HIV prevalence among tested women who knew their serostatus was 9.6%. Besides age, the sole independent predictor of a positive serostatus was having experienced forced sex by men, by women, or by both men and women. Study findings indicate that despite the image of invulnerability, HIV/AIDS is a reality for lesbian and bisexual women in Southern Africa. Surprisingly, it is not sex with men per se, but rather forced sex that is the important risk factor for self-reported HIV infection among the participating women. HIV/AIDS policy should also address the needs of lesbian, bisexual and other women who have sex with women.
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