Recent HIV infections among newly diagnosed individuals living with HIV in rural Lesotho: Secondary data from the VIBRA cluster-randomized trial.

BACKGROUND: HIV recency assays are used to distinguish recently acquired infection from long-term infection among individuals newly diagnosed with HIV. Since 2015, the World Health Organisation recommends the use of an algorithm to assess recency of infections which is based on an HIV recency assay and viral load (VL) quantification. We determined the proportion of recent HIV infections among participants of the VIBRA (Village-Based Refill of Antiretroviral therapy) cluster-randomized trial in Lesotho and assessed risk factors for these recent infections. METHODS: The VIBRA trial recruited individuals living with HIV and not taking antiretroviral therapy during a door-to-door HIV testing campaign in two rural districts (Butha-Buthe and Mokhotlong). Samples were collected from participants newly diagnosed and tested for HIV recency using the Asanté HIV-1 Rapid Recency Assay and VL using the Roche Cobas System. Clinical and socio-demographic data were extracted from the trial database. Univariate analysis was conducted to determine factors associated with recent compared to long-term infection. RESULTS: Participants were recruited from August 2018 to May 2019 and 184 patient-samples included in this study. The majority were female (108 [59%]) with a median age of 36 years (interquartile range 30-50 years). We found 13 (7.0%) recent infections, while 171 (93.0%) were classified as long-term HIV infections. No conclusive evidence for risk factors of recent infection was found. CONCLUSIONS: During door-to-door testing among a general population sample in rural Lesotho, 7% of those who were newly diagnosed had acquired HIV in the preceding 6 months. More efforts and research are needed to curb ongoing transmissions in these rural communities.

Tracking the rate of initiation and retention on isoniazid preventive therapy in a high human immunodeficiency virus and tuberculosis burden setting of Lesotho.

BACKGROUND: Tuberculosis (TB) remains a public health problem, particularly in people living with human immunodeficiency virus (PLHIV). Yet, efforts to reduce TB incidence using isoniazid preventive therapy (IPT) have been curtailed by poor uptake of this intervention. This study reviewed the rate of IPT initiation in the sub-Saharan country of Lesotho, which has one of the highest TB incidences in the world. METHODS: Time to IPT initiation in randomly sampled medical records of PLHIV was analysed using Cox's proportional hazards regression. Differences in the periods of enrolment into Human immunodeficiency virus (HIV) care were controlled for by considering the year IPT was launched (2011) as the base year and stratifying the medical records into the 2004-2010 cohort (before the launch of IPT) and the 2011-2016 cohort (after the launch). RESULTS: Out of 2955 patients included in the final analysis, 68.8% had received IPT by the study exit time. However, the overall rate of IPT initiation was 20.6 per 100 person-years, with 135 (6.6%) treatment interruptions. Compared to the 2004-2010 cohort, the 2011-2016 had a significantly (p < 0.05) higher rate of initiation (15.8 vs. 27.0 per 100 person-years, respectively). Age group, district category and duration of antiretroviral therapy emerged as the most significant predictors of IPT initiation, while district category and gender significantly predicted IPT therapy interruption. CONCLUSION: These findings indicate a high uptake of IPT with a slow rate of implementation. Significant factors associated with disparities in the initiation and interruption of IPT therapy in this study are important for policy review.

Molecular evolutionary dynamics of cytochrome P450 monooxygenases across kingdoms: Special focus on mycobacterial P450s.

Since the initial identification of cytochrome P450 monooxygenases (CYPs/P450s), great progress has been made in understanding their structure-function relationship, diversity and application in producing compounds beneficial to humans. However, the molecular evolution of P450s in terms of their dynamics both at protein and DNA levels and functional conservation across kingdoms still needs investigation. In this study, we analyzed 17 598 P450s belonging to 113 P450 families (bacteria -42; fungi -19; plant -28; animal -22; plant and animal -1 and common P450 family -1) and found highly conserved and rapidly evolving P450 families. Results suggested that bacterial P450s, particularly P450s belonging to mycobacteria, are highly conserved both at protein and DNA levels. Mycobacteria possess the highest P450 diversity percentage compared to other microbes and have a high coverage of P450s (≥1%) in their genomes, as found in fungi and plants. Phylogenetic and functional analyses revealed the functional conservation of P450s despite belonging to different biological kingdoms, suggesting the adherence of P450s to their innate function such as their involvement in either generation or oxidation of steroids and structurally related molecules, fatty acids and terpenoids. This study's results offer new understanding of the dynamic structural nature of P450s.

The effect of tenofovir in renal function in HIV-positive adult patients in the Roma health service area, Lesotho, southern Africa.

INTRODUCTION: The government of Lesotho introduced tenofovir disoproxil fumarate (TDF) for first-line antiretroviral treatment (ART), as recommended by the World Health Organization (1), in 2008. The use of TDF has been associated with renal toxicity (2); furthermore, renal function outcomes following the use of TDF has not been studied at Roma Health Service Area (RHSA) in Lesotho. Lesotho is a small landlocked country surrounded by South Africa. The study used an analytical design to compare retrospective creatinine clearance (CrCl) data of 312 (64%) antiretroviral treatment naïve adults exposed to TDF and 173 (36%) unexposed patients. METHODS: Impaired renal function was defined as CrCl less than 50 mL/min calculated using the Cockcroft-Gault equation. The Ministry of Health and Social Welfare of Lesotho approved the study on 13 January 2012. The study included adult (excluding pregnant females) HIV patients enrolled on ART between December 2006 and December 2012 at St Joseph's Mission Hospital and at Nazareth Health Centre (RHSA). Patients at Nazareth Health Centre and at St Joseph's Mission Hospital made up 80% of the circa 4 116 HIV patients on ART. Only 485 patients met the set inclusion criteria. RESULTS: In 56 patients (17.9%), TDF was found to be contraindicated. The use of TDF was marginally significant factor for renal toxicity (p=0.054) in univariate analysis, but was insignificant (p=0.122) in multivariate logistic analysis. Univariate (p<0.1) and multivariate logistic regression (p<0.05) were performed using STATA(®) 11. Female gender (p=0.016), hypertension (p=0.009), and age>60 (p=0.004) were significantly associated with CrCl<50 mL/min outcome. CONCLUSIONS: In this study, TDF proofed to be a weak contributing factor of renal impairment. Routine baseline renal function screening should however be adopted to prevent patients with impaired renal function receiving TDF.