Genetic Factors Associated with Slow Progression of HIV among Perinatally-Infected Indian Children.

Objectives: To study the association between common AIDS restriction genes and slow disease progression among perinatally-infected children in India. Methods: ART-naïve children were identified and selected host factors including CCR5-Δ32, SDF1-3’A, CCR5-59029G, HLA-B*27, B*57 were studied using allele-specific PCR-RFLP and SSPGo HLA typing kits. Results: Among 165 children, 10 (6%) long-term non-progressors and 8 (5%) slow progressors were identified. For comparison, 12 children with normal progression of HIV were included. The frequencies of CCR5-Δ32 deletion, SDF1-3’A and CCR5-59029G did not differ significantly. HLA-B*27 and B*57 were observed only in long-term non-progressors or slow progressors, who also harbored either SDF1-3’A and/or CCR5-59029G. Conclusions: There is an association between host genetic factors and slow disease progression in this population.

Dried blood spot HIV-1 RNA quantification: A useful tool for viral load monitoring among HIV-infected individuals in India.

Background & objectives: Monitoring of HIV-infected individuals on antiretroviral treatment (ART) ideally requires periodic viral load measurements to ascertain adequate response to treatment. While plasma viral load monitoring is widely available in high-income settings, it is rarely used in resource-limited regions because of high cost and need for sophisticated sample transport. Dried blood spot (DBS) as source specimens for viral load measurement has shown promise as an alternative to plasma specimens and is likely to be a useful tool for Indian settings. The present study was undertaken to investigate the performance of DBS in HIV-1 RNA quantification against the standard plasma viral load assay. Methods: Between April-June 2011, 130 samples were collected from HIV-1-infected (n=125) and non-infected (n=5) individuals in two district clinics in southern India. HIV-1 RNA quantification was performed from DBS and plasma using Abbott m2000rt system after manual RNA extraction. Statistical analysis included correlation, regression and Bland-Altman analysis. Results: The sensitivity of DBS viral load was 97 per cent with viral loads >3.0 log10 copies/ml. Measurable viral load (>3.0 log10 copies/ml) results obtained for the 74 paired plasma-DBS samples showed positive correlation between both the assays (r=0.96). For clinically acceptable viral load threshold values of >5,000 copies/ml, Bland-Altman plots showed acceptable limits of agreement (-0.21 to +0.8 log10 copies/ml). The mean difference was 0.29 log10 copies/ml. The cost of DBS was $2.67 lower compared to conventional plasma viral load measurement in the setting. Interpretation & conclusions: The significant positive correlation with standard plasma-based assay and lower cost of DBS viral load monitoring suggest that DBS sampling can be a feasible and economical means of viral load monitoring in HIV-infected individual in India and in other resource-limited settings globally.

Genetic architecture of HIV-1 genes circulating in north India & their functional implications.

This review presents data on genetic and functional analysis of some of the HIV-1 genes derived from HIV-1 infected individuals from north India (Delhi, Punjab and Chandigarh). We found evidence of novel B/C recombinants in HIV-1 LTR region showing relatedness to China/Mynmar with 3 copies of Nfκb sites; B/C/D mosaic genomes for HIV-1 Vpr and novel B/C Tat. We reported appearance of a complex recombinant form CRF_02AG of HIV-1 envelope sequences which is predominantly found in Central/Western Africa. Also one Indian HIV-1 envelope subtype C sequence suggested exclusive CXCR4 co-receptor usage. This extensive recombination, which is observed in about 10 per cent HIV-1 infected individuals in the Vpr genes, resulted in remarkably altered functions when compared with prototype subtype B Vpr. The Vpu C was found to be more potent in causing apoptosis when compared with Vpu B when analyzed for subG1 DNA content. The functional implications of these changes as well as in other genes of HIV-1 are discussed in detail with possible implications for subtype-specific pathogenesis highlighted.

Community prevalence of methicillin and vancomycin resistant Staphylococcus aureus in and around Bangalore, southern India / Prevalência de Staphylococcus aureus resistente à meticilina e à vancomicina em comunidade no entorno de Bangalore, Índia do Sul

INTRODUCTION: Staphylococcus aureus is a known colonizer in humans and has been implicated in community acquired soft tissue infections. However emergence of methicillin resistant S. aureus (MRSA) has aroused great concern worldwide. This study aimed to determine the prevalence of MRSA in the community of Bangalore, southern India. METHODS: Swabs were collected from anterior nares, forearm, dorsum and palm of the hands of 1,000 healthy individuals residing in and around Bangalore, belonging to different socioeconomic strata and age groups. RESULTS: Analysis verified that 22.5 percent and 16.6 percent of the individuals presented Staphylococcus aureus and MRSA, respectively, at any of the three sites. Vancomycin resistance was observed in 1.4 percent of the S. aureus isolates, which was confirmed by detection of the vanA gene. It was interesting to note that 58.8 percent of the children in the age group 1-5 years-old presented MRSA, the highest percentage compared to other age groups of < 1 (44.4 percent) year-old, 5-20 (21.7 percent) years-old, > 40 (11 percent) years-old and 20-40 (9.9 percent) years-old. Among the population of various socioeconomic strata, maximum MRSA colonization was observed among doctors (22.2 percent), followed by upper economic class (18.8 percent), lower economic class (17.7 percent), apparently healthy hospital in-patients (16.5 percent), nurses (16 percent) and middle economic class (12.5 percent). Most of the MRSA isolates were capsular polysaccharide antigen type 8 (57.1 percent). CONCLUSIONS: There is a need for continuous surveillance and monitoring of the presence of MRSA in the community and a clearer understanding of the dynamics of the spread of MRSA will assist in controlling its dissemination.

INTRODUÇÃO: O Staphylococcus aureus é conhecido por ser um colonizador em humanos sendo implicado em infecções comunitárias dos tecidos moles. Contudo, a resistência à meticilina e emergência de S. aureus meticilina resistentes (MRSA) têm despertado preocupação em todo o mundo. O presente estudo visa encontrar a prevalência de MRSA na comunidade de Bangalore, sul da Índia. MÉTODOS: Suabes foram coletados de narinas anteriores, antebraço e dorso da palma de 1.000 indivíduos saudáveis, residentes em Bangalore e nas proximidades, pertencentes a diferentes estratos socioeconômicos e faixas etárias. RESULTADOS: Observou-se que 22,5 por cento e 16,6 por cento dos indivíduos foram abrigar Staphylococcus aureus e MRSA, respectivamente, em qualquer um dos três locais. Dos S. aureus isolados, 1,4 por cento também foram resistentes à vancomicina, o que foi confirmado pela detecção do gene vanA. Foi interessante notar que 58,8 por cento das crianças na faixa etária de 1-5 anos foram abrigar MRSA, o mais elevado em comparação com outros grupos etários de < 1 (44,4 por cento) ano, 50-20 (21,7 por cento) anos, > 40 (11 por cento) anos e 20-40 (9,9 por cento) anos. Entre a população de diferentes estratos socioeconômicos, a colonização de MRSA máxima foi observada entre os médicos (22,2 por cento), seguida pela classe econômica superior (18,8 por cento), classe baixa (17,7 por cento), pacientes aparentemente saudáveis (16,5 por cento), enfermeiros (16 por cento) e classe econômica média (12,5 por cento). A maioria dos MRSA isolados eram do tipo polissacarídeo capsular antígeno 8 (57,1 por cento). CONCLUSÕES: Há uma necessidade de vigilância e monitorização contínua da presença de MRSA na comunidade, bem como uma melhor compreensão da dinâmica de propagação de MRSA pode ajudar no controle da disseminação.