Retention in pre-antiretroviral treatment care in a district of Karnataka, India: how well are we doing?

Setting: Antiretroviral treatment (ART) Centre in Tumkur district of Karnataka State, India. There is no published information about pre-ART loss to follow-up from India. Objective: To assess the proportion lost to follow-up (defined as not visiting the ART Centre within 1 year of registration) and associated socio-demographic and immunological variables. Design: Retrospective cohort study involving a review of medical records of adult HIV-infected persons (aged ⩾15 years) registered in pre-ART care during January 2010–June 2012. Results: Of 3238 patients registered, 2519 (78%) were eligible for ART, while 719 (22%) were not. Four of the latter were transferred out; the remaining 715 individuals were enrolled in pre-ART care, of whom 290 (41%) were lost to follow-up. Factors associated with loss to follow-up on multivariate analysis included age group ⩾45 years, low educational level, not being married, World Health Organization Stage III or IV and rural residence. Conclusion: About four in 10 individuals in pre-ART care were lost to follow-up within 1 year of registration. This needs urgent attention. Routine cohort analysis in the national programme should include those in pre-ART care to enable improved review, monitoring and supervision. Further qualitative research to ascertain reasons for loss to follow-up is required to design future interventions

HIV/AIDS-tuberculosis (pulmonary and extra pulmonary) co-infection: CD4 correlation

Background: AIDS is the leading cause of death among people 15-59 years old in low income countries. Worldwide, approximately one-third of all AIDS-related deaths are associated with TB. TB is the primary cause of death for 10-15% of patients with HIV infection. So the present study was conducted to find the correlation between sputum positivity and CD4 cell count in patients with HIV/AIDS-Tuberculosis co-infection.Methods: The present study was a retrospective hospital based study of patients with HIV/AIDS-Tuberculosis co-infection, attending ART centre, department of medicine, Osmania general hospital, Hyderabad, Telangana, India between November 2014 to September 2015. Data included clinical profile, complete blood picture, renal and liver function tests, sputum microscopy and C/S and chest X-Ray and others as and when required.Results: We included 180 HIV/AIDS infected patients on ART with tuberculosis (TB) co-infection. Out of 180 patients, 132 were males and 48 were females. Among male’s ≥40 (51.51%) year’s age group and among females 30-39 (56.25%) year’s age group was the most commonly affected. Out of 180 cases 60 were sputum positive. 60 sputum negative pulmonary tuberculosis and 60 were extra pulmonary TB. CD4 cell count was <200/mm3 in 36 (60%) of sputum positive TB, 43 (71.7%) of sputum negative pulmonary TB & 39 (65%) of extra pulmonary TB patients. CD4 cell count was 200-400/mm3 in 16(26.7%) of sputum positive pulmonary TB, 13 (21.7%) of sputum negative TB and 19 (31.7%) of extra pulmonary TB patients. CD4 cell count was >400/mm3 in 8 (13.3%) of sputum positive pulmonary TB, 4 (6.6%) of sputum negative pulmonary TB and 2 (3.3%) of extra pulmonary TB patients.Conclusions: Present study concludes that male sex and age group >30 years were the commonly affected population. All forms of tuberculosis were common when CD4 count was <200 cells/mm3. The sputum negativity was higher with lower CD4 counts.

Antenatal testing for anaemia, HIV and syphilis in Indonesia - a health systems analysis of low coverage

BackgroundAdverse pregnancy outcomes can be prevented through the early detection and treatment of anaemia, HIV and syphilis during the antenatal period. Rates of testing for anaemia, HIV and syphilis among women attending antenatal services in Indonesia are low, despite its mandate in national guidelines and international policy.MethodsMidwife-held antenatal care records for 2015 from 8 villages in 2 sub-districts within Cianjur district were reviewed, alongside the available sub-district Puskesmas (Community Health Centre) maternity and laboratory records. We conducted four focus group discussions with kaders (community health workers) (n = 16) and midwives (n = 9), and 13 semi-structured interviews with laboratory and counselling, public sector maternity and HIV management and relevant non-governmental organisation staff. Participants were recruited from village, sub-district, district and national level as relevant to role.ResultsWe were unable to find a single recorded result of antenatal testing for HIV, syphilis or anaemia in the village (566 women) or Puskesmas records (2816 women) for 2015. Laboratory records did not specifically identify antenatal women. Participants described conducting and reporting testing in a largely ad hoc manner; relying on referral to health facilities based on clinical suspicion or separate non-maternity voluntary counselling and testing programs. Participants recognized significant systematic challenges with key differences between the more acceptable (and reportedly more often implemented) haemoglobin testing and the less acceptable (and barely implemented) HIV and syphilis testing. However, a clear need for leadership and accountability emerged as an important factor for prioritizing antenatal testing and addressing these testing gaps.ConclusionsPractical solutions such as revised registers, availability of point-of-care tests and capacity building of field staff will therefore need to be accompanied by both funding and political will to coordinate, prioritize and be accountable for testing in pregnancy

Effectiveness of isoniazid preventive therapy on incidence of tuberculosis among HIV-infected adults in programme setting

Background & objectives: As India and other developing countries are scaling up isoniazid preventive therapy (IPT) for people living with HIV (PLHIV) in their national programmes, we studied the feasibility and performance of IPT in terms of treatment adherence, outcome and post-treatment effect when given under programmatic settings. Methods: A multicentre, prospective pilot study was initiated among adults living with HIV on isoniazid 300 mg with pyridoxine 50 mg after ruling out active tuberculosis (TB). Symptom review and counselling were done monthly during IPT and for six-month post-IPT. The TB incidence rate was calculated and risk factors were identified. Results: Among 4528 adults living with HIV who initiated IPT, 4015 (89%) successfully completed IPT. IPT was terminated in 121 adults (3%) due to grade 2 or above adverse events. Twenty five PLHIVs developed TB while on IPT. The incidence of TB while on IPT was 1.17/100 person-years (p-y) [95% confidence interval (CI) 0.8-1.73] as compared to TB incidence of 2.42/100 p-y (95% CI 1.90-3.10) during the pre-IPT period at these centres (P=0.017). The incidence of TB post-IPT was 0.64/100 p-y (95% CI 0.04-1.12). No single factor was significantly associated with the development of TB. Interpretation & conclusions: Under programmatic settings, completion of IPT treatment was high, adverse events minimal with good post-treatment protection. After ruling out TB, IPT should be offered to all PLHIVs, irrespective of their antiretroviral therapy (ART) status. Scaling-up of IPT services including active case finding, periodic counselling on adherence and re-training of ART staff should be prioritized to reduce the TB burden in this community

Effectiveness of symptom screening and incidence of tuberculosis among adults and children living with HIV infection in India.

BACKGROUND WHO recommends the use of a simplified symptom-based algorithm for screening for tuberculosis (TB) among people living with HIV (PLHIV). We assessed the feasibility and effectiveness of this algorithm and determined the prevalence and incidence of TB among PLHIV attending antiretroviral treatment (ART) centres in India. METHODS We did a prospective multicentric implementation research study in four states of India. To rule out TB, we administered the WHO symptom-screen algorithm to all PLHIV every month for 6 months. If they were found to be symptomatic any time during this period, they were referred for investigations for TB. A case of TB diagnosed during the first month of screening was taken as a prevalent case while those detected TB in the subsequent 5 months were considered cases of incident TB. We calculated the incidence rate using the person-years method. Results . Between May 2012 and October 2013, a total of 6099 adults and 1662 children living with HIV were screened for TB at the ART centres of four states. Of the 6099 adult PLHIV, 1815 (30%) had at least one symptom suggestive of TB, of whom only 634 (35%) were referred for investigations of TB. Of those referred, 97 (15%) PLHIV were diagnosed with TB. Overall, the prevalence of undiagnosed TB was 0.84 person-years and in the subsequent period, the incidence of TB was 2.4/100 person-years (95% CI 1.90-3.10). Among 1662 children, 434 (26%) had at least one symptom suggestive of TB. But only 57 (13%) children were referred for investigations of TB and 13 (23%) of them were diagnosed with TB. The prevalence of TB among children was 0.5% and its incidence among them was 2.7/100 person-years (95% CI 1.60-4.30). CONCLUSION Prevalence and incidence of TB is high among PLHIV attending ART centres. This emphasizes the need to strengthen regular screening for symptoms of TB and further referral of those symptomatic for diagnosis of TB

Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas

<p>Abstract</p> <p>Background</p> <p>Loss of heterozygosity of chromosome 10q26 has been shown to be associated with the aggressiveness of astrocytic tumors (or astrocytomas), but the responsible gene(s) residing in this region has not been fully identified. The <it>BCCIP </it>gene is located at chromosome 10q26. It encodes a BRCA2 and CDKN1A (p21) interacting protein. Previous studies have shown that down-regulation of BCCIP impairs recombinational DNA repair, G1/S cell cycle checkpoint, p53 trans-activation activity, cytokinesis, and chromosome stability, suggesting a potential role of <it>BCCIP </it>in cancer etiology. In this study, we investigated whether <it>BCCIP </it>is altered in astrocytomas.</p> <p>Methods</p> <p>Genomic DNA from 45 cases of grade IV astrocytic tumor (glioblastoma) tissues and 12 cases of normal tissues were analyzed by quantitative PCR. The BCCIP protein expression in 96 cases of grade II–IV astrocytic tumors was detected by immunohistochemistry (IHC). IHC staining of glial fibrillary acid protein (GFAP), a marker for astrocytic cells, was used to identify cells of the astrocytic lineage.</p> <p>Results</p> <p>We found that BCCIP protein is expressed in normal cells with positive staining of GFAP. However, BCCIP protein expression was not detectable in ~45% of all astrocytic tumors, and in > 60% in the grade IV glioblastoma. About 45% glioblastoma have significant (p < 0.01) reduction of <it>BCCIP </it>gene copy number when compared to normal DNA. Furthermore, the frequency of lacking BCCIP expression is associated with the aggressiveness of astrocytic tumors.</p> <p>Conclusion</p> <p>Our data implicate a role of BCCIP in astrocytic tumorigenesis, and lack of <it>BCCIP </it>may be used as a marker for astrocytomas.</p

Adherence to Drug-Refill Is a Useful Early Warning Indicator of Virologic and Immunologic Failure among HIV Patients on First-Line ART in South Africa

Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa.In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12-99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO).After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2-6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2-3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02).One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure

Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches