African HIV-positive Patients Research Articles

HPLC-MS identification and expression of Candida drug-resistance proteins from African HIV-infected patients.

The objective of this study was to elucidate the proteomic mechanisms of drug resistance in HIV-infected African patients. Cell membrane fractions from forty oral Candida isolates isolated from African HIV-positive patients were analysed using HPLC-MS with the aim of identifying proteins associated with their pathogenicity and drug resistance. Heat shock proteins that mediate the fungicidal activity of salivary peptides were found in all tested Candida fractions, with pH-responsive proteins associated with increased pathogenicity only being present in the three most commonly isolated species. ABC multidrug transporter efflux pumps and estrogen binding proteins were only found in C. albicans fractions, while ergosterol biosynthesis proteins were identified in four species. The combination of various adherence, invasion, upregulation and efflux pump mechanisms appear to be instrumental for the Candida host colonization and drug resistance emergence in HIV-infected individuals.

The Association of Immune Markers with Cognitive Performance in South African HIV-Positive Patients.

Dysregulated expression of neuro-immune markers has previously been linked to HIV-associated neurocognitive impairment. We undertook an exploratory approach in a HIV clade-C cohort, investigating the association between eight immune markers and neurocognitive performance in 99 HIV+ and 51 HIV- participants. Markers were selected on preliminary and putative evidence of their link to key neuro-immune functions. Cognitive performance was established using a battery of tests sensitive to HIV-associated neurocognitive impairment, with domain-based scores utilized in analysis. The markers Thymidine phosphorylase (TYMP) and Neutrophil gelatinase-associated lipocalin (NGAL) were significantly higher while Matrix Metalloproteinase (MMP)9 was significantly lower in HIV+ participants. Our results further showed that in the HIV+ group, worse psychomotor processing speed was associated with higher TYMP and NGAL levels and worse motor function was associated with higher NGAL levels. Future studies should explore the underlying mechanisms of these markers in HIV-associated neurocognitive impairment. Graphical Abstract The association of peripheral immune markers with neurocognitive performance in South African HIV-positive patients.

Increased CD4 counts, pain and depression are correlates of lower sleep quality in treated HIV positive patients with low baseline CD4 counts

Poor sleep quality leads to increased immune activation and immune activation leads to worse sleep quality. South African HIV positive patients typically have delayed start of treatment, which has been associated with CD4+ effector T cells being more spontaneously activated in chronically treated patients. This cross-sectional study investigated whether subjective sleep quality was associated with CD4+ T lymphocyte reconstitution in treated South African HIV+ patients.One hundred and thirty-nine treated HIV+ patients (109 F, age average (SD) = 43 (9)) were recruited from Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, South Africa. Participants completed questionnaires evaluating their subjective sleep quality (Pittsburgh Sleep Quality Index), daytime sleepiness (Epworth sleepiness scale), pain, and depression severity (Beck Depression Inventory). Univariate and multivariate analyses were run to determine the correlates of sleep quality in this population.Patients had been on antiretroviral treatment for about 4 years and had increased their CD4 counts from a median at baseline of 82 to 467 cells/µL. They had overall poor sleep quality (average (SD) PSQI = 7.7 (±5), 61% reporting PSQI > 5, a marker of lower sleep quality), 41% had clinical depression (average (SD) BDI = 17 (±12)) and 55% reported pain. In two separate multivariate analyses, both the overall CD4 count increase from baseline (p = 0.0006) and higher current CD4 counts (p = 0.0007) were associated with worse sleep quality, when adjusting for depression severity (p < 0.001), daytime sleepiness (p = 0.01) and the presence of pain (p < 0.01).In this cohort of treated South African HIV positive patients, poor sleep quality was associated with higher current CD4 counts, when adjusting for depression severity, daytime sleepiness and pain. Further studies should investigate the temporal relationship between HIV-related poor sleep quality and underlying immune activation.

Diffuse infiltrative lymphocytosis syndrome presenting as renal failure in South African HIV-positive individuals: a single-centre case series

Diffuse infiltrative lymphocytosis syndrome (DILS) in human immunodeficiency virus (HIV) infection presented most commonly with parotidomegaly and sicca symptoms in the pre-antiretroviral era. However, numerous clinical manifestations are possible due to the multi-organ nature of the CD8+ lymphocytic infiltration. Renal involvement is infrequently described, but common characteristics of a renal syndrome associated with DILS have been identified. This case series describes four South African HIV-positive patients with DILS, in whom renal failure was the sole clinical manifestation. As DILS responds well to antiretroviral and corticosteroid therapy, this series highlights the importance of considering this syndrome as a cause of renal failure in an HIV-positive patient.

Consenting to HIV-positive organ donation in the USA: legal and ethical considerations in comparison with a South African context

Consenting to HIV-positive organ donation in the USA: legal and ethical considerations in comparison with a South African context Elmi Muller Department of Surgery, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa Abstract: Since 2008, 43 HIV positive-to-positive transplants have been performed in Cape Town, South Africa. The ethical decision to utilize HIV-positive donors had been informed by a very unique clinical situation in South Africa. South African transplant recipients are generally young, black patients from low socioeconomic groups where treatment options for their end-stage renal disease are limited. Dialysis is not freely available in the country and strict admission criteria exist to access this treatment option. Because South African patients are competing for scarce resources, with many HIV-positive as well as negative patients unable to access dialysis treatment, a transplant with an HIV-positive organ is an acceptable treatment option to many HIV-positive patients in this country. Furthermore, South African HIV-positive patients are generally young and often have low rates of comorbid disease making them ideal transplant candidates. In the USA, HIV-positive patients are generally older and dialysis is freely available to them. Transplantation with HIV-negative organs as well as dialysis are treatment options available to USA-based HIV-positive patients – an important difference to South African patients. Finally, the HIV-positive deceased donors in South Africa are often young trauma victims where HIV is diagnosed at the time of death and the patient is naïve to antiretroviral therapy (ART). In general, South Africa has very low ART resistance rates and a fairly uniform subtype C HIV in the country. This means that using a deceased donor who had been exposed to ART before has a different clinical risk than in the USA, where most donors had been treated with ART and seldom are trauma victims. The author debates in this article how this unique scenario makes use of HIV-positive donors in the USA differently in comparison with South Africa. Keywords: HIV positive, transplantation, deceased donation, HIV positive-to-positive

Differences in genetic variants in lopinavir disposition among HIV-infected Bantu Africans.

Variability in lopinavir (LPV) plasma concentration among patients could be due to genetic polymorphisms. This study set to evaluate significance of variants in CYP3A4/5, SLCO1B1 and ABCC2 on LPV plasma concentration among African HIV-positive patients. Eighty-six HIV-positive participants on ritonavir (LPV/r) were genetically characterized and LPV plasma concentration determined. LPV plasma concentrations differed >188-fold (range 0.0206-38.6 µg/ml). Both CYP3A4*22 and SLCO1B1 rs4149056G (c.521C) were not observed in this cohort. CYP3A4*1B, CYP3A5*3, CYP3A5*6 and ABCC2 c.1249G>A which have been associated with LPV plasma concentration, showed no significant association. These findings highlight the need to include African groups in genomics research to identify variants of pharmacogenomics significance.

Immature platelet fraction levels in a variety of bone marrow pathologies in South African HIV-positive patients with thrombocytopenia

ObjectivesThrombocytopenia is common in HIV-infected individuals and often requires a diagnostic bone marrow examination. Interpretation may, however, be limited due to the multifactorial nature of HIV-associated thrombocytopenia and the difficulty in assessing megakaryocyte function morphologically. The immature platelet fraction (IPF) is a parameter which reportedly reflects megakaryocyte activity, with an IPF >7.7% suggesting increased platelet production. The aim of this study was to correlate the IPF with the bone marrow findings as well as other clinical variables of interest in South African patients with HIV-associated thrombocytopenia.MethodsSeventy-eight HIV-positive patients with thrombocytopenia were enrolled from the Charlotte Maxeke Johannesburg Academic Hospital. The IPF levels were measured using a Sysmex XE-5000 haematology analyzer and were correlated with bone marrow and other findings.ResultsThe median IPF was 7.6%, ranging from 1.3 to 44%. It was raised in 78% of patients with immune thrombocytopenia (ITP) (median = 16.3%) and low in 79% of patients with hypocellular marrow (median = 6.5%). Surprisingly, it was highly variable among patients with malignant marrow infiltration and mycobacterial infection of the bone marrow (BMTB) (median = 8.4 and 7.1%, respectively). Mulitivariate linear regression analysis confirmed a significant independent inverse relationship between the IPF and hypocellular marrow (P < 0.0001), a marginally significant positive association with ITP (P = 0.059), and the absence of any relationship with malignant infiltration or BMTB. The IPF had a significant inverse association with the platelet count (P = 0.0006), but was unrelated to the CD4 count and exposure to anti-retroviral therapy. Unexpectedly, it showed a significant positive association with the HIV viral load (P = 0.005). We speculate this to reflect increased megakaryocyte activity in compensation for accelerated platelet clearance due to HIV-driven platelet activation.ConclusionThis study investigates the role of the IPF in HIV-associated thrombocytopenia, and emphasizes the limitations of morphological analysis in determining megakaryocyte function.

Polymorphisms in uncoupling protein genes UCP2 and UCP3 are not associated with HIV‐associated sensory neuropathy in African individuals

Dear Editor,Human immunodeficiency virus-associated sen-sory neuropathy (HIV-SN), due to viral and/or drug-related toxicity, is the most common neurologicalcomplication of HIV (Sacktor, 2002) and causes sig-nificant suffering and reduced quality of life (Ellis et al.,2010). The neuropathy shares several features withdiabetic neuropathy, for example, both HIV-SN anddiabetic neuropathy are small-fibre, length-dependentneuropathies that are associated with mitochondrialdysfunction and intracellular calcium dysregulation(Verkhratsky and Fernyhough, 2008; Hoke et al., 2009;Lehmann et al., 2011).Recently, minor alleles in the genes encodingmitochondrial uncoupling proteins UCP2(rs659366*A,-866G

The prevalence and burden of pain and other symptoms among South Africans attending highly active antiretroviral therapy (HAART) clinics

Since the advent of antiretrovirals, HIV disease has largely come to be considered a chronic disease for those able to access treatment. As such, the concept of 'living well' with HIV is important. Increasing evidence suggests a high symptom burden in HIV that persists in the presence of treatment. Our study aimed to measure the prevalence and burden of pain and other physical and psychological symptoms among South African HIV-positive patients attending highly active antiretroviral therapy (HAART) clinics. The study design was a cross-sectional survey. Simple random sampling was used to recruit 385 adult participants. The sample had a median age of 40 years (Q1 - Q3=33 - 46) and 98.4% were on HAART. The mean latest CD4 count for the participants was 355.06±219/mm³. The mean number of symptoms of the 32 symptoms on the MSAS-SF experienced by participants was 10.24±5.71 (range 1 - 28). All 4 psychological symptoms were in the top 10 most prevalent symptoms, with feeling sad being the most prevalent symptom overall. The high prevalence of symptoms and the high symptom burden experienced by the participants in this survey suggest inadequate symptom control and highlight the palliative care needs of an ambulant patient population already on HAART. Extension of life without reasonable efforts to also address the patient's quality of life is not ethically justifiable. In addition, more research appears to be required to answer whether these findings are associated with sub-optimal HAART adherence.

Screening African HIV positive patients for imported parasitic infections

To assess the results of screening for tropical parasitic infections in HIV patients from Africa, presenting to an infectious diseases unit in the UK. A retrospective case note review of patients from Sub-Saharan Africa, newly diagnosed with HIV infection, between March 2001 and November 2007. Data on patient demographics, clinical presentation and laboratory results, including tropical screening tests, were collected. 146 patients had notes available for review. 22 different countries were represented. 84 patients were screened, by serology, for schistosomiasis, strongyloidiasis, filariasis and leishmaniasis. 13/122 (10.7%) patients tested had positive schistosomiasis serology and 2/107 (1.9%) had positive strongyloidiasis serology. No patients had positive Leishmania (n = 108) or filaria (n = 97) serology. 3 of 38 (7.9%) had stool samples that were positive for pathogens. Positive schistosomiasis serology was associated with male sex (61.5% vs 28.4% p < 0.05) and a higher mean eosinophil count (0.46 vs 0.12 cells/microL p < 0.0001). Screening HIV patients from Sub-Saharan Africa for schistosomiasis in this population, was positive in over 1 in 10 patients. We would recommend screening for schistosomiasis in these patients. Our results do not support serological screening for leishmaniasis or filarial infection in these patients.

Validation of the Wisconsin Brief Pain Questionnaire in a Multilingual South African Population

Assessment of pain intensity and its effect on quality of life is important for proper management of pain, but no validated pain assessment tools that assess pain intensity and the interference pain has on daily life are available in indigenous South African languages. Therefore, the aim of this study was to validate translated versions of the Wisconsin Brief Pain Questionnaire (WBPQ) in South African HIV-positive patients. The WBPQ was translated into three indigenous South African languages, Setswana, isiZulu, and Xitsonga. We interviewed 452 ambulatory HIV-positive patients (327 urban and 125 rural patients) between the ages of 20 and 76 years old. Factor analysis to assess construct validity identified a two-factor structure (pain intensity and pain interference) for the isiZulu ( n = 132), Xitsonga ( n = 125), and Setswana ( n = 66) versions of the WBPQ, whereas a three-factor structure (pain intensity, mood interference, and activity interference) was identified for the English (completed by English second-language speakers, n = 129) version of the WBPQ. Cronbach alphas, calculated to assess the reliability of the pain intensity and pain interference scales, were greater than 0.70 for all scales in all four versions of the WBPQ, showing internal consistency within the dimensions. These results provide evidence of validity for an easily administered questionnaire, which assesses pain intensity and pain interference, in three indigenous South African languages, and for English second-language speakers, in a population of South African HIV-positive patients.

The symptoms of autonomic dysfunction in HIV-positive Africans

Human immunodeficiency virus (HIV) infection is associated with autonomic neuropathy. The resultant autonomic dysfunction impairs quality of life and can have fatal consequences. Our aim was to clearly define the symptoms of autonomic dysfunction in African HIV-positive patients and determine whether these symptoms were related with (a) autonomic reflex responses (b) the degree of immunosupression. Thirty-one HIV-positive treatment-naïve African patients (mean CD4 cell count 269.5 +/- 253.4/mm3) and 12 healthy controls completed a detailed questionnaire (Autonomic System Profile, Mayo Clinic, Rochester, MN) relating to specific symptoms of autonomic dysfunction. After completion of the questionnaire, subjects underwent a standard battery of autonomic reflex tests. The autonomic symptom score was higher in the male HIV-positive patients (26.7 +/- 14.7 points) and female patients with CD4 <200/mm3 (24.7 +/- 18.0) than sex-matched controls (male controls, 9.9 +/- 6.8, P < 0.05; female controls, 8.8 +/- 10.1; P < 0.05). Six patients had scores indicative of severe autonomic dysfunction (>43.8 points). The most common autonomic symptoms were: orthostatic intolerance, secretomotor and gastrointestinal dysfunction. There was no relationship between CD4 cell counts and autonomic symptom scores. The blood pressure response to sustained handgrip was blunted, but all other cardiovascular reflex tests were within the normal range or borderline. African HIV-positive patients report symptoms of autonomic dysfunction, despite normal or borderline autonomic reflex responses.

Pattern of neuropsychological performance among HIV positive patients in Uganda

BackgroundFew studies have examined cognitive functioning of HIV positive patients in sub-Saharan Africa. It cannot be assumed that HIV positive patients in Africa exhibit the same declines as patients in high-resource settings, since there are differences that may influence cognitive functioning including nutrition, history of concomitant disease, and varying HIV strains, among other possibilities. Part of the difficulty of specifying abnormalities in neuropsychological functioning among African HIV positive patients is that there are no readily available African normative databases. The purpose of the current study was to evaluate the pattern of neuropsychological performance in a sample of HIV positive patients in comparison to HIV negative control subjects in Uganda.MethodsThe neuropsychological test scores of 110 HIV positive patients (WHO Stage 2, n = 21; WHO Stage 3, n = 69; WHO Stage 4, n = 20) were contrasted with those of 100 control subjects on measures of attention/concentration, mental flexibility, learning/memory, and motor functioning.ResultsAnalysis of covariance (ANCOVA) revealed significant group differences on measures of verbal learning and memory, speed of processing, attention and executive functioning between HIV seropositive and seronegative subjects.ConclusionUgandan patients with HIV demonstrated relative deficits on measures of verbal learning and memory, speed of processing, attention, and executive functioning compared to HIV negative controls. These results from a resource limited region where clades A and D are prevalent are consistent with previous findings in the developed world where clade B predominates.

Stroke in black South African HIV-positive patients: a prospective analysis.

Stroke associated with HIV infection is poorly characterized. In this study we analyze the association in a black African population. The clinical, laboratory, and radiological characteristics of 35 hospital-based black South African, heterosexual, HIV-infected patients who did not abuse intravenous drugs and presented with strokes were prospectively studied. The patients were antiretroviral therapy naive. Patients with other intracranial space-occupying lesions were excluded from the study. The age range was 20 to 61 years (mean, 32.1 years). There were 21 female and 14 male patients, with a female to male ratio of 1.5:1. Cerebral infarction occurred in 33 patients (94%) and intracerebral hemorrhage in 2 patients (6%). Underlying causes were identified in 30 of the 35 patients (86%) and included coagulopathies, meningitis, cardioembolism, and hypertension. The most common coagulopathy was protein S deficiency. No cause was found in 5 patients (14%). The results are similar to data from studies on young black African stroke patients who are HIV negative.

HE2000 AIDS drug shows promise in clinical trials

HE2000 AIDS drug shows promise in clinical trials

Pulmonary tuberculosis in HIV infection: Radiographic appearance is related to CD4 + T-lymphocyte count

Setting: An adult HIV outpatient clinic in Cape Town, South Africa. Objective: To investigate the relationship between the radiographic appearance of pulmonary tuberculosis (PTB) in HIV infected patients and CD4 + T-lymphocyte count. Design: Pretreatment radiographs of 150 patients with newly diagnosed PTB were reviewed. CD4 + Tlymphocyte count was used as a marker of HIV disease progression. Results: Upper zone infiltrate typical of PTB reactivation was present in 18 patients. This pattern was associated with early HIV infection (mean CD4 + T-cell count 389) and had 78% positive predictive value for identifying patients with > 200 CD4 + T-lymphocytes/μL. Pleural effusion was present in 32 patients and occurred over a wide intermediate range of CD4 + T-cell counts (mean 185). Lower or midzone infiltrates, adenopathy, interstitial pattern or normal radiograph occurred in 136 patients and were associated with advanced HIV disease (mean CD4 + T-cell count 105). These patterns had 84%, 89%, 89% and 100% positive predictive value, respectively, for identifying patients with < 200 CD4 + T-cells/μL. Conclusion: Pulmonary tuberculosis in African HIV-positive patients presents with a spectrum of radiographic abnormalities, and specific patterns are predictive of stage of HIV disease progression. In patients dually infected with HIV and PTB, chest radiographs are a useful adjunct to clinical staging.