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Discusses the risk of human immunodeficiency virus-1 infection in twin pairs born to infected mothers in Malawi. Detection of infections through polymerase chain reaction; Analysis of birth order and delivery as risk factors; Impact of birth order on postnatal transmission rates.

As antiretroviral drugs become widely available in developing countries, practical, field-friendly, and cheap methods of measuring CD4+ lymphocyte counts need to be developed. We tested use of whole blood spots dried on filter paper to measure CD4+ lymphocyte counts. We obtained blood from 42 HIV-1-infected patients from Zambia. We dried blood spots on filter paper and measured CD4+ lymphocyte counts with an established commercial enzyme immunoassay. We compared these measurements with those obtained from matched liquid whole-blood samples analysed with standard flow cytometry. Results of the filter-paper method accorded well with flow cytometry CD4 counts greater than 200 cells/ L (mean difference 13.6 [SD 52.4]). Dried whole blood stored on filter paper could be developed into a field-friendly alternative for CD4+ lymphocyte count measurements. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor regarding George Janossy's views on dried blood spot technology and focuses on the complexity of therapeutic monitoring of HIV-1-infected patients in Africa.

Few studies have examined immune activation profiles in patients with advanced HIV-1 subtype C infection or assessed their potential to predict responsiveness to HAART. BioPlex, ELISA, and nephelometric procedures were used to measure plasma levels of inflammatory biomarkers in HIV-1 subtype C-infected patients sampled before and after 6months of successfulHAART (n = 20); in patients failingHAART (n = 30); and in uninfected controls (n = 8). Prior toHAART, CXCL9, CXCL10, β2M, sTNF-R1, TGF-β1, IFN-γ, IL-6, TNF, and sCD14 were significantly elevated in HIV-1-infected patients compared to controls (p < 0.01). All of these markers, with the exception of sTNF-R1, were also elevated in patients failingHAART (p < 0.05).The persistently elevated levels of CXCL9, CXCL10, and β2M in patients failing therapy in the setting of amarked reduction in thesemarkers in patients on successful HAART suggest that they may be useful not only to monitor immune activation during HAART, but also to distinguish between good and poor responders. In the case of sCD14 and TGF-β1, the levels of these biomarkers remained persistently elevated despite HAART-induced virological suppression, a finding that is consistent with ongoing monocyte-macrophage activation, underscoring a potential role for adjuvant anti-inflammatory therapy. [ABSTRACT FROM AUTHOR]

Background. Human immunodeficiency virus type 1 (HIV-1) infection is associated with a massive depletion of intestinal CD4+ T cells that is only partially reversed by combination antiretroviral therapy (cART). Here, we assessed the ability of nucleoside reverse-transcriptase inhibitor/nonnucleoside reverse-transcriptase inhibitor treatment to restore the CD4+ T-cell populations in the intestine of South African patients with AIDS.Methods. Thirty-eight patients with advanced HIV-1 infection who had chronic diarrhea (duration, >4 weeks) and/or unintentional weight loss (>10% decrease from baseline) of uncertain etiology were enrolled. Blood specimens were collected monthly, and gastrointestinal tract biopsy specimens were collected before cART initiation (from the duodenum, jejunum, ileum, and colon), 3 months after cART initiation (from the duodenum), and 6 months after cART initiation (from the duodenum and colon). CD4+, CD8+, and CD38+CD8+ T cells were quantified by flow cytometry and immunohistochemistry analyses, and the HIV-1 RNA load was determined by the Nuclisens assay.Results. CD4+ T-cell and HIV-1 RNA levels were significantly lower, whereas CD8+ T-cell levels, including activated CD38+CD8+ T cell levels, were higher in the duodenum and jejunum, compared with the colon. After 6 months of cART, a significant but incomplete recovery of CD4+ T cells was detected in the colon and peripheral blood but not in the duodenum. Failed restoration of the CD4+ T-cell count in the duodenum was associated with nonspecific enteritis and CD8+ T-cell activation.Conclusions. Strategies that target inflammation and immune activation in the small intestine may be required to expedite CD4+ T-cell recovery and improve therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Background. Microbial translocation contributes to immune activation and disease progression during chronic human immunodeficiency virus type 1 (HIV-1) infection. However, its role in the African AIDS epidemic remains controversial. Here, we investigated the relationship between markers of monocyte activation, plasma lipopolysaccharide (LPS), and HIV-1 RNA in South Africans prioritized to receive combination antiretroviral therapy (cART).Methods. Ten HIV-1-negative African controls and 80 HIV-1-infected patients with CD4 T cell counts <200 cells/µL were sampled prior to (n = 60) or during (n = 20) receipt of effective cART. Viral load was measured by Nuclisens; LPS by the Limulus amoebocyte lysate assay; monocyte and T cell subsets by flow cytometry; and soluble CD14, cytokines, and chemokines by enzyme-linked immunosorbent assay and customized Bio-Plex plates.Results. Three distinct sets of markers were identified. CCL2, CXCL10, and CD14+ CD16+ monocyte levels were positively correlated with HIV-1 viremia. This finding, together with cART-induced normalization of these markers, suggests that their upregulation was driven by HIV-1. Plasma interleukin-6 was associated with the presence of opportunistic coinfections. Soluble CD14 and tumor necrosis factor were linked to plasma LPS levels and, as observed for LPS, remained elevated in patients receiving effective cART.Conclusions. Microbial translocation is a major force driving chronic inflammation in HIV-infected Africans receiving cART. Prevention of monocyte activation may be especially effective at enhancing therapeutic outcomes. [ABSTRACT FROM PUBLISHER]

The article reports on the use of the oligonucleotide ligation assay (OLA) as a test for detecting HIV-1 drug resistance mutations in resource-poor areas. The OLA is an inexpensive and sensitive ligase-based point mutation assay used in detecting HIV-1 drug-resistance mutations. HIV-1 specimens were collected from seven international laboratories and used in OLA. It was found that laboratories knowledgeable in molecular techniques can use the OLA.

The article discusses a study on pneumonia in children caused by the HIV virus. The author notes that the main cause of children being admitted to hospitals in southern Africa is HIV-related pneumonia. According to the author, the aim of the study is to measure the cause and predictors of treatment failure in children with severe pneumonia in Durban, South Africa. The author cites polymicrobial disease as an important factor in treatment failure. He notes the need to develop low-cost diagnostic methods to aid clinicians.

HIV, the cause of AIDS in humans, is characterized by great genetic heterogeneity. In particular, HIV-1 group M subtypes are responsible for most of the infections worldwide. We investigate the demographic history of HIV-1B and HIV-1C subtypes in South Africa and Brazil using both a parametric and a nonparametric approach based on coalescent theory. Our results show that although both subtypes are spreading exponentially in Brazil, the HIV-1C growth rate is about twice that of Brazilian HIV-1B or South African HIV-1C, providing evidence, for the first time, of a different epidemic potential between two HIV-1 subtypes. The present study not only may have important consequences for devising future vaccination and therapeutic strategies, but also offers additional evidence that skyline plots are indeed a simple and powerful tool for monitoring and predicting the behavior of viral epidemics. [ABSTRACT FROM AUTHOR]

Most Internet online resources for investigating HIV biology contain either bioinformatics tools, protein information or sequence data. The objective of this study was to develop a comprehensive online proteomics resource that integrates bioinformatics with the latest information on HIV-1 protein structure, gene expression, post-transcriptional/post-translational modification, functional activity, and protein-macromolecule interactions. The BioAfrica HIV-1 Proteomics Resource http://bioafrica.mrc.ac.za/proteomics/index.html is a website that contains detailed information about the HIV-1 proteome and protease cleavage sites, as well as data-mining tools that can be used to manipulate and query protein sequence data, a BLAST tool for initiating structural analyses of HIV-1 proteins, and a proteomics tools directory. The Proteome section contains extensive data on each of 19 HIV-1 proteins, including their functional properties, a sample analysis of HIV-1HXB2, structural models and links to other online resources. The HIV-1 Protease Cleavage Sites section provides information on the position, subtype variation and genetic evolution of Gag, Gag-Pol and Nef cleavage sites. The HIV-1 Protein Data-mining Tool includes a set of 27 group M (subtypes A through K) reference sequences that can be used to assess the influence of genetic variation on immunological and functional domains of the protein. The BLAST Structure Tool identifies proteins with similar, experimentally determined topologies, and the Tools Directory provides a categorized list of websites and relevant software programs. This combined database and software repository is designed to facilitate the capture, retrieval and analysis of HIV-1 protein data, and to convert it into clinically useful information relating to the pathogenesis, transmission and therapeutic response of different HIV-1 variants. The HIV-1 Proteomics Resource is readily accessible through the BioAfrica website at: http://bioafrica.mrc.ac.za/proteomics/index.html [ABSTRACT FROM AUTHOR]

To investigate transmission of human herpesvirus (HHV)-8, 2546 mother-child pairs were recruited from rural clinics in South Africa and were tested for antibodies against lyric and latent HHV-8 antigens. The prevalence of antibodies in children increased with increasing maternal antibody titer (lyric, χ12 = 26, and P<.001; latent, χ12 = 55, and P<.001). HHV-8 DNA was detectable in 145 of 978 maternal saliva samples (mean virus load, 488,450 copies/mL; range, 1550–660,000 copies/mL) and in 12 of 43 breast-milk samples (mean virus load, 5800 copies/mL; range, 1550–12,540 copies/mL). The prevalence of HHV-8 DNA in maternal saliva was unrelated to latent anti-HHV-8 antibody status but was higher in mothers with the highest titers of lyric antibodies than in other mothers (34% vs. 8%; P < .001). The prevalence of lyric anti-HHV-8 antibodies in children was 13% (70/528) if the mother did not have HHV-8 in saliva and was 29% (8/28) if the mother had a high HHV-8 load (>50,000 copies/mL) in saliva (odds ratio, 2.6; 95% confidence interval, 1.1–6.2). The presence of HHV-8 DNA in maternal saliva was unrelated to latent antibodies in children. Saliva could be a route of transmission of HHV-8 from person to person, although other routes cannot be ruled out. [ABSTRACT FROM AUTHOR]

Reports on a pilot study in an urban tuberculosis (TB) clinic in South Africa to determine the feasibility and effectiveness of integrating highly active antiretroviral therapy (HAART) into existing TB directly observed therapy programs. Offer of HIV counseling and testing for patients with smear-positive pulmonary TB; Treatment regimen for the HIV-positive patients; Tolerance for the treatment with minimal gastrointestinal, hepatic, skin and neurologic toxicity.

Naturally occurring polymorphisms in the protease of human immunodeficiency virus type 1 (HIV-1) subtype C would be expected to lead to adaptive (compensatory) changes in protease cleavage sites. To test this hypothesis, we examined the prevalences and patterns of cleavage site polymorphisms in the Gag, Gag-Pol, and Nef cleavage sites of C compared to those in non-C subtypes. Codon-based maximum-likelihood methods were used to assess the natural selection and evolutionary history of individual cleavage sites. Seven cleavage sites (p17/p24, p24/p2, NC/p1, NC/TFP, PR/RT, RT/p66, and p66/IN) were well conserved over time and in all HIV-1 subtypes. One site (p1/p6[sup gag]) exhibited moderate variation, and four sites (p2/NC, TFP/p6[sup pol], p6[sup pol]/PR, and Nef) were highly variable, both within and between subtypes. Three of the variable sites are known to be major determinants of polyprotein processing and virion production. P2/NC controls the rate and order of cleavage, p6[sup gag] is an important phosphoprotein required for virion release, and TFP/p6[sup pol], a novel cleavage site in the transframe domain, influences the specificity of Gag-Pol processing and the activation of protease. Overall, 58.3% of the 12 HIV-1 cleavage sites were significantly more diverse in C than in B viruses. When analyzed as a single concatenated fragment of 360 bp, 96.0% of group M cleavage site sequences fell into subtype-specific phylogenetic clusters, suggesting that they coevolved with the virus. Natural variation at C cleavage sites may play an important role, not only in regulation of the viral cycle but also in disease progression and response to therapy. [ABSTRACT FROM AUTHOR]

Examines the phylogenetic relationships among the six supposedly nonrecombinant primate lentiviruses (PLV) lineages. Employment of bootscanning as an exploratory tool; Existence of at least five putative recombinant fragments in the PLV genome; Hypothesis of the simian immunodeficiency viruses and their simian hosts.

Host genetic factors may influence the course of human immunodeficiency virus (HIV) infection. In Blantyre, Malawi, polymerase chain reaction was used to identify twin pairs who were concordantly HIV-1-infected in utero or perinatally and then to examine strain divergence or virus levels in identical and fraternal twin pairs. Among 315 twin pairs, both infants in 14 fraternal and 5 identical pairs were found to be infected at the same visit. Among 10 pairs, HIV-1 sequences were determined for both infants at ≥1 time point. HIV levels had a common profile in both fraternal and identical twin pairs. Identical twins were not always infected by the same quasi species, indicating that their mothers had multiple quasi species capable of infecting their infants. Subsequent viral divergence appears to depend on quasispecies stability rather than on genetically controlled host immune responses. Thus, given infection, factors intrinsic to HIV-1 are more important than host genetics in viral evolution. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Microbial Translocation: The Innate Cytokine Response, and HIV-1 Disease Progression in Africa," by A. D. Redd, D. Dabitao, J. H. Bream, and colleagues in the March 1, 2011 issue.

A letter to the editor regarding the scientific contributions of AIDS researcher Robert C. Gallo is presented.

In 1998, outbreaks of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infection were reported in children attending Al-Fateh Hospital in Benghazi, Libya. Here we use molecular phylogenetic techniques to analyse new virus sequences from these outbreaks. We find that the HIV-1 and HCV strains were already circulating and prevalent in this hospital and its environs before the arrival in March 1998 of the foreign medical staff (five Bulgarian nurses and a Palestinian doctor) who stand accused of transmitting the HIV strain to the children. [ABSTRACT FROM AUTHOR]

Discusses the rate of vertical transmission of HIV (from mothers to children) in South Africa. Effects of breast-feeding on the transmission; Effects of antiretroviral drugs on the spread of the disease; Idea that half of vertical transmission cases could be prevented by short-course antiretroviral drug regimens; Issue of drug-resistance.