Attenuation of immune activation in an open-label clinical trial for HIV-AIDS using a polyherbal formulation.

To explain a stable clinical outcome observed in a previous pilot clinical trial using a polyherbal formulation (PHF) for HIV-AIDS, we, in the present study, evaluated the T cell functions from fresh and stored blood samples. In three clinical groups-the anti-retroviral therapy, PHF and control arms-we compared the circulating levels of lipopolysaccharide, LPS-binding protein, soluble CD14, aspartate transaminase (AST) and alanine transaminase (ALT). Additionally, we evaluated the expression of T cell markers and gag-specific immune responses. The PHF treatment significantly reduced the levels of sCD14, AST and ALT. In a cross-sectional analysis at 30 months post-treatment, in comparison to the control group, the PHF arm showed significantly low per-cell expression of PD1, CD95 and HLA-DR. The PHF treatment appears to have attenuated general immune activation and hepatic inflammation in the study participants. Targeting the mediators of immune activation must be pursued as a useful strategy for HIV-AIDS management.

Evident stabilization of the clinical profile in HIV/AIDS as evaluated in an open label clinical trial using a polyherbal formulation.

BACKGROUND & OBJECTIVES: The complementary and alternative medicines (CAM) have not been systematically evaluated for the management of HIV/AIDS patients. In a prospective, single-site, open-label, non-randomized, controlled, pilot trial, we evaluated a polyherbal formulation (PHF) for its safety and efficacy in treating subjects with HIV-AIDS. METHODS: A total of 32 and 31 subjects were enrolled under the PHF and highly active antiretroviral treatment (HAART) arms, respectively, and followed up for a period of 24 months. Plasma viral RNA, CD4 cell count and blood chemistry were monitored at 3-month intervals. Following mid-term safety evaluation, 12 subjects from the PHF arm were shifted to HAART and were followed separately as PHF-to-HAART arm, for the rest of the period. RESULTS: The HAART arm was characterized by significant improvements in CD4 cell count (154.4 cells/µl/year, P<0.001) and reduction in plasma viral load within 3 to 6 months (-0.431+ 0.004 log 10 IU/month, P<0.001). In contrast, the PHF arm showed a profile of CD4 cell loss at remarkably slower kinetics (14.3 cells/µl/year, P=0.021) and insignificant reduction in the viral load. The PHF and HAART arms did not differ significantly in the occurrence of AIDS-related illnesses over the study period of 24 months. In the PHF-to-HAART arm, the rates of CD4 count and reduction in viral load were significant and comparable to that of the HAART group. In the PHF arm, at 1 month, a significant increase in CD4 cell count and a concomitant decrease in viral load were seen. INTERPRETATION & CONCLUSIONS: The PHF appears to have provided protection by delaying the kinetics of CD4 cell reduction. Given the several study limitations, drawing assertive inferences from the data is challenging. Future studies with a stringent study design are warranted to confirm these findings.

Multiple NF-κB sites in HIV-1 subtype C long terminal repeat confer superior magnitude of transcription and thereby the enhanced viral predominance.

We demonstrate that at least three different promoter variant strains of HIV-1 subtype C have been gradually expanding and replacing the standard subtype C viruses in India, and possibly in South Africa and other global regions, over the past decade. The new viral strains contain an additional NF-κB, NF-κB-like, or RBEIII site in the viral promoter. Although the acquisition of an additional RBEIII site is a property shared by all the HIV-1 subtypes, acquiring an additional NF-κB site remains an exclusive property of subtype C. The acquired κB site is genetically distinct, binds the p50-p65 heterodimer, and strengthens the viral promoter at the levels of transcription initiation and elongation. The 4-κB viruses dominate the 3-κB "isogenic" viral strains in pairwise competition assays in T-cell lines, primary cells, and the ecotropic human immunodeficiency virus mouse model. The dominance of the 4-κB viral strains is also evident in the natural context when the subjects are coinfected with κB-variant viral strains. The mean plasma viral loads, but not CD4 counts, are significantly different in 4-κB infection suggesting that these newly emerging strains are probably more infectious. It is possible that higher plasma viral loads underlie selective transmission of the 4-κB viral strains. Several publications previously reported duplication or deletion of diverse transcription factor-binding sites in the viral promoter. Unlike previous reports, our study provides experimental evidence that the new viral strains gained a potential selective advantage as a consequence of the acquired transcription factor-binding sites and importantly that these strains have been expanding at the population level.

HLA-B57 and gender influence the occurrence of tuberculosis in HIV infected people of south India.

BACKGROUND: Substantial evidence exists for HLA and other host genetic factors being determinants of susceptibility or resistance to infectious diseases. However, very little information is available on the role of host genetic factors in HIV-TB coinfection. Hence, a longitudinal study was undertaken to investigate HLA associations in a cohort of HIV seropositive individuals with and without TB in Bangalore, South India. METHODS: A cohort of 238 HIV seropositive subjects were typed for HLA-A, B, and DR by PCR-SSP and followed up for 5 years or till manifestation of Tuberculosis. HLA data of 682 HIV Negative healthy renal donors was used as control. RESULTS: The ratio of males and females in HIV cohort was comparable (50.4% and 49.6%). But the incidence of TB was markedly lower in females (12.6%,) than males (25.6%). Further, HLA-B*57 frequency in HIV cohort was significantly higher among females without TB (21.6%, 19/88) than males (1.7%, 1/59); P = 0.0046; OR = 38. CD4 counts also were higher among females in this cohort. CONCLUSION: This study suggests that HIV positive women with HLA-B*57 have less occurrence of TB as compared to males.

Adherence to anti-retroviral therapy among HIV patients in Bangalore, India.

INTRODUCTION: Human Immunodeficiency Virus (HIV) has an estimated prevalence of 0.9% in India (5.2 million). Anti-retroviral drugs (ARV) are the treatments of choice and non-adherence is an important factor in treatment failure and development of resistance, as well as being a powerful predictor of survival. This study assesses adherence to ARV in HIV positive patients in Bangalore, India, a country where only 10% of those who need therapy are receiving it. METHODS: A cross-sectional anonymous questionnaire survey of 60 HIV antibody positive patients was carried out with patients attending HIV outpatient services at two centres: The Chest and Maternity Centre, Rajajinagar, and Wockhardt Hospital and Heart Institute, Bangalore. Consent was obtained. Translation was done by a translator and doctors where required. Data was analysed using SPSS statistical analysis. RESULTS: A response rate of 88% (53/60) was achieved. The mean patient age was 39.98 years, with 50% aged 30-40, and 73.6% of participants being male. Mean family size was 4.8 (1-13). 21% lived less than 50 kms and 21% greater than 400 kms from clinic.60% reported they were fully adherent. Adherence was statistically significantly linked to regular follow-up attendance (70.5%, p = 0.002). No other results were statistically significant but trends were found. "100% adherence" trends were seen in older patients, male gender, those from larger families, those who had a previous AIDS defining illness, those taking fewer tablets, and without food restrictions. Commonest side-effects causing non-adherence were metabolic reasons (66%) and GI symptoms (50%). No trends were seen for education level, family income, distance travelled to clinic, time since diagnosis, or time on ART. CONCLUSION: Regular attendance for follow up was statistically significant for 100% lifetime adherence. Positive trends were seen in those in larger families, older, those who had AIDS defining illness, simple regimes, and without side-effects. Education, income, distance travelled and length of time diagnosed or treated had no effect on adherence.