HIV-1 preferentially infects M. tuberculosis-specific CD4+ T cells due to their increased production of IL-2.

The characteristics of loop-mediated isothermal amplification (LAMP) make it a promising platform for the molecular detection of tuberculosis (TB) in developing countries. Here, we report on the first clinical evaluation of LAMP for the detection of pulmonary TB in microscopy centers in Peru, Bangladesh, and Tanzania to determine its operational applicability in such settings. A prototype LAMP assay with simplified manual DNA extraction was evaluated for accuracy and ease of use. The sensitivity of LAMP in smear-and culture-positive sputum specimens was 97.7% (173/177 specimens; 95% confidence interval [CI], 95.5 to 99.9%), and the sensitivity in smear-negative, culture-positive specimens was 48.8% (21/43 specimens; CI, 33.9 to 63.7%). The specificity in culture-negative samples was 99% (500/505 specimens; CI, 98.1 to 99.9%). The average hands-on time for testing six samples and two controls was 54 min, similar to that of sputum smear microscopy. The optimal amplification time was 40 min. No indeterminate results were reported, and the interreader variability was 0.4%. Despite the use of a single room without biosafety cabinets for all procedures, no DNA contamination was observed. The assay was robust, with high end-point stability and low rates of test failure. Technicians with no prior molecular experience easily performed the assay after 1 week of training, and opportunities for further simplification of the assay were identified.

Background The acid-fast bacillus Mycobacterium tuberculosis (MTB) is often the first manifestation of AIDS in HIV infected patients. This study was conducted to better understand the mechanism underlying MTB-specific pathogenicity early in HIV infection. Methods MTB-specific T Helper 1 (TH1) cells were studied in HIV negative (n=114) and chronically HIV infected (n=68) Tanzanian subjects usinEarly Secreted Antigenic Target 6 (ESAT6) protein or Tuberculin (PPD) by Interferon gamma (IFNγ) ELISPOT and intracellular cytokine staining. In a longitudinal study the effect of acute HIV infection on MTB-specific TH1 cells was determined by polychromatic flow cytometric analysis in 5 subjects with latent MTB infection, who became infected with HIV. Results In Tuberculosis (TB) asymptomatic subjects, chronic HIV infection was associated with a decreased frequency of responders with detectable MTB-specific TH1 cells (p-value = 0.0003) that was not observed in subjects with active TB. Acute HIV infection induced a rapid depletion of MTB-specific TH1 cells in 4 subjects who remained TB asymptomatic, but were stable in subjects who remained HIV negative (p<0.01). Conclusions Together these data suggest a mechanism of rapid MTB-specific TH1 cell depletion that may contribute to the early onset of TB in latently MTB infected individuals who become HIV infected.

ObjectiveLinkage to care is the bridge between HIV testing and HIV treatment, care and support. In Tanzania, mobile testing aims to address historically low testing rates. Linkage to care was reported at 14% in 2009 and 28% in 2014. The study compares linkage to care of HIV-positive individuals tested at mobile/outreach versus public health facility-based services within the first 6 months of HIV diagnosis.SettingRural communities in four districts of Mbeya Region, Tanzania.ParticipantsA total of 1012 newly diagnosed HIV-positive adults from 16 testing facilities were enrolled into a two-armed cohort and followed for 6 months between August 2014 and July 2015. 840 (83%) participants completed the study.Main outcome measuresWe compared the ratios and time variance in linkage to care using the Kaplan-Meier estimator and Log rank tests. Cox proportional hazards regression models to evaluate factors associated with time variance in linkage.ResultsAt the end of 6 months, 78% of all respondents had linked into care, with differences across testing models. 84% (CI 81% to 87%, n=512) of individuals tested at facility-based site were linked to care compared to 69% (CI 65% to 74%, n=281) of individuals tested at mobile/outreach. The median time to linkage was 1 day (IQR: 1–7.5) for facility-based site and 6 days (IQR: 3–11) for mobile/outreach sites. Participants tested at facility-based site were 78% more likely to link than those tested at mobile/outreach when other variables were controlled (AHR=1.78; 95% CI 1.52 to 2.07). HIV status disclosure to family/relatives was significantly associated with linkage to care (AHR=2.64; 95% CI 2.05 to 3.39).ConclusionsLinkage to care after testing HIV positive in rural Tanzania has increased markedly since 2014, across testing models. Individuals tested at facility-based sites linked in significantly higher proportion and modestly sooner than mobile/outreach tested individuals. Mobile/outreach testing models bring HIV testing services closer to people. Strategies to improve linkage from mobile/outreach models are needed.

Background In remote rural Tanzania, the rate of linkage into HIV care was estimated at 28% in 2014. This study explored facilitators and barriers to linkage to HIV care at individual/patient, health care provider, health system, and contextual levels to inform eventual design of interventions to improve linkage to HIV care. Methods We conducted a descriptive qualitative study nested in a cohort study of 1012 newly diagnosed HIV-positive individuals in Mbeya region between August 2014 and July 2015. We conducted 8 focus group discussions and 10 in-depth interviews with recently diagnosed HIV-positive individuals and 20 individual interviews with healthcare providers. Transcripts were analyzed inductively using thematic content analysis. The emergent themes were then deductively fitted into the four level ecological model. Results We identified multiple factors influencing linkage to care. HIV status disclosure, support from family/relatives and having symptoms of disease were reported to facilitate linkage at the individual level. Fear of stigma, lack of disclosure, denial and being asymptomatic, belief in witchcraft and spiritual beliefs were barriers identified at individual’s level. At providers’ level; support and good patient-staff relationship facilitated linkage, while negative attitudes and abusive language were reported barriers to successful linkage. Clear referral procedures and well-organized clinic procedures were system-level facilitators, whereas poorly organized clinic procedures and visit schedules, overcrowding, long waiting times and lack of resources were reported barriers. Distance and transport costs to HIV care centers were important contextual factors influencing linkage to care. Conclusion Linkage to HIV care is an important step towards proper management of HIV. We found that access and linkage to care are influenced positively and negatively at all levels, however, the individual-level and health system-level factors were most prominent in this setting. Interventions must address issues around stigma, denial and inadequate awareness of the value of early linkage to care, and improve the capacity of HIV treatment/care clinics to implement quality care, particularly in light of adopting the ‘Test and Treat’ model of HIV treatment and care recommended by the World Health Organization.