Hepatitis B and HIV co-infection in pregnant women: Indication for routine antenatal hepatitis B virus screening in a high HIV prevalence setting

Background. Sub-Saharan Africa is endemic for hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections. HBV/HIV co-infection in women of reproductive age is of clinical and public health importance because these women constitute a significant reservoir for horizontal and perinatal HBV transmission. Childhood HBV vaccination from 6 weeks of age protects most children against chronic HBV infection. However, infants born to HBV/HIV co-infected women are more likely to be infected perinatally, with an increased risk of chronic hepatitis, than infants born to HBV mono-infected women.Objectives. The aim of our study was to establish the prevalence of HBV infection and HBV/HIV co-infection in pregnant women in KwaZulu-Natal, South Africa, to inform antenatal HBV screening and childhood immunisation policies in South Africa.Methods. Stored plasma specimens obtained from 570 pregnant women were tested for hepatitis B surface antigen (HBsAg) and HBV infectivity, as characterised by the presence of hepatitis B e antigen (HBeAg) and/or HBV DNA load.Results. The antenatal HIV prevalence and HBsAg prevalence in this study were 41.6% and 5.3% (95% confidence interval (CI) 3.4 - 7.1%), respectively. Overall, 3.1% (95% CI 1.7 - 4.6%) of pregnant women were HBV/HIV co-infected, with HBeAg positivity and the HBV DNA load being significantly higher in co-infected women.Conclusion. We report a 5.3% HBV prevalence and a 3.1% HBV/HIV co-infection prevalence in pregnant women from this HIV-endemic region. Routine antenatal HBV screening will allow early identification of neonates who require HBV active-passive immunoprophylaxis at birth. This strategy, together with antenatal antiretrovirals, will reduce the risk of perinatal HBV transmission, especially in high-risk HBV/HIV co-infected pregnant women

Evaluation of antenatal rapid human immunodeficiency virus testing in rural South Africa

Introduction: South African guidelines recommend two rapid tests for diagnosing human immunodeficiency virus (HIV) using the serial HIV testing algorithm, but the accuracy and compliance to this algorithm is unknown in rural clinics. We evaluated the accuracy of HIV rapid testing and the time to receiving test results among pregnant women in rural KwaZulu-Natal (KZN).Method: We observed the accuracy of rapid HIV testing algorithms for 208 consenting antenatal patients accessing voluntary HIV testing services in nine rural primary healthcare (PHC) clinics in KZN. A PHC-based HIV counsellor obtained finger-prick whole blood from each participant to perform rapid testing using the Advanced Quality™ One Step anti-HIV (1&2) and/or ABON™ HIV 1/2/O Tri-Line HIV test. A research nurse obtained venous blood for an enzyme-linked immunosorbent assay (ELISA) HIV test, which is the gold standard diagnostic test. We recorded the time of receipt of HIV test results for each test.Results: Among 208 pregnant women with a mean age of 26 years, 72 women from nine rural PHC clinics were identified as HIV-positive by two rapid tests with an HIV-prevalence of 35% (95% Bayesian credibility intervals [BCI]: 28% – 41%). Of the 208 patients, 135 patients from six clinics were tested with the serial HIV testing algorithm. The estimated sensitivity and specificity for the 135 participants were 100% (95% confidence interval [CI]: 93% – 100%) and 99% (CI: 95% – 100%), respectively. The positive predictive value and negative predictive value were estimated at 98% (CI: 94% – 100%) and 95% (CI: 88% – 99%), respectively. All women received their HIV rapid test results within 20 min of testing. Test stock-out resulted in poor test availability at point-of-care, preventing performance of a second HIV test in three out of nine PHC clinics in rural KZN.Conclusion: Despite the poor compliance with national guidelines for HIV rapid testing services, HIV rapid test results provided to pregnant women in rural PHC clinics in KZN were generally accurate and timely. Test stock-out was shown to be one of the barriers to test availability in rural PHC clinics, resulting in poor compliance with guidelines. We recommend a compulsory confirmation HIV rapid test for all HIV-negative test results obtained from pregnant patients in rural and resource-limited settings

Southern African Treatment Resistance Network (SATuRN) RegaDB HIV drug resistance and clinical management database: supporting patient management, surveillance and research in southern Africa

Substantial amounts of data have been generated from patient management and academic exercises designed to better understand the human immunodeficiency virus (HIV) epidemic and design interventions to control it. A number of specialized databases have been designed to manage huge data sets from HIV cohort, vaccine, host genomic and drug resistance studies. Besides databases from cohort studies, most of the online databases contain limited curated data and are thus sequence repositories. HIV drug resistance has been shown to have a great potential to derail the progress made thus far through antiretroviral therapy. Thus, a lot of resources have been invested in generating drug resistance data for patient management and surveillance purposes. Unfortunately, most of the data currently available relate to subtype B even though >60% of the epidemic is caused by HIV-1 subtype C. A consortium of clinicians, scientists, public health experts and policy markers working in southern Africa came together and formed a network, the Southern African Treatment and Resistance Network (SATuRN), with the aim of increasing curated HIV-1 subtype C and tuberculosis drug resistance data. This article describes the HIV-1 data curation process using the SATuRN Rega database. The data curation is a manual and time-consuming process done by clinical, laboratory and data curation specialists. Access to the highly curated data sets is through applications that are reviewed by the SATuRN executive committee. Examples of research outputs from the analysis of the curated data include trends in the level of transmitted drug resistance in South Africa, analysis of the levels of acquired resistance among patients failing therapy and factors associated with the absence of genotypic evidence of drug resistance among patients failing therapy. All these studies have been important for informing first- and second-line therapy. This database is a free password-protected open source database available on www.bioafrica.net

Impact of pretreatment low-abundance HIV-1 drug-resistant variants on virological failure among HIV-1/TB-co-infected individuals.

OBJECTIVES: To determine the impact of pretreatment low-abundance HIV-1 drug-resistant variants (LA-DRVs) on virological failure (VF) among HIV-1/TB-co-infected individuals treated with NNRTI first-line ART. METHODS: We conducted a case-control study of 170 adults with HIV-1/TB co-infection. Cases had at least one viral load (VL) ≥1000 RNA copies/mL after ≥6 months on NNRTI-based ART, and controls had sustained VLs <1000 copies/mL. We sequenced plasma viruses by Sanger and MiSeq next-generation sequencing (NGS). We assessed drug resistance mutations (DRMs) using the Stanford drug resistance database, and analysed NGS data for DRMs at ≥20%, 10%, 5% and 2% thresholds. We assessed the effect of pretreatment drug resistance (PDR) on VF. RESULTS: We analysed sequences from 45 cases and 125 controls. Overall prevalence of PDR detected at a ≥20% threshold was 4.7% (8/170) and was higher in cases than in controls (8.9% versus 3.2%), P = 0.210. Participants with PDR at ≥20% had almost 4-fold higher odds of VF (adjusted OR 3.7, 95% CI 0.8-18.3) compared with those without, P = 0.104. PDR prevalence increased to 18.2% (31/170) when LA-DRVs at ≥2% were included. Participants with pretreatment LA-DRVs only had 1.6-fold higher odds of VF (adjusted OR 1.6, 95% CI 0.6-4.3) compared with those without, P = 0.398. CONCLUSIONS: Pretreatment DRMs and LA-DRVs increased the odds of developing VF on NNRTI-based ART, although without statistical significance. NGS increased detection of DRMs but provided no additional benefit in identifying participants at risk of VF at lower thresholds. More studies assessing mutation thresholds predictive of VF are required to inform use of NGS in treatment decisions

Spatial patterns of extensively drug-resistant tuberculosis transmission in KwaZulu-Natal, South Africa

BACKGROUND : Transmission is driving the global drug-resistant tuberculosis (TB) epidemic; nearly three-quarters of drug-resistant TB cases are attributable to transmission. Geographic patterns of disease incidence, combined with information on probable transmission links, can define the spatial scale of transmission and generate hypotheses about factors driving transmission patterns. METHODS : We combined whole-genome sequencing data with home Global Positioning System coordinates from 344 participants with extensively drug-resistant (XDR) TB in KwaZulu-Natal, South Africa, diagnosed from 2011 to 2014. We aimed to determine if genomically linked (difference of ≤5 single-nucleotide polymorphisms) cases lived close to one another, which would suggest a role for local community settings in transmission. RESULTS : One hundred eighty-two study participants were genomically linked, comprising 1084 case-pairs. The median distance between case-pairs’ homes was 108 km (interquartile range, 64–162 km). Between-district, as compared to within-district, links accounted for the majority (912/1084 [84%]) of genomic links. Half (526 [49%]) of genomic links involved a case from Durban, the urban center of KwaZulu-Natal. CONCLUSIONS : The high proportions of between-district links with Durban provide insight into possible drivers of province-wide XDR-TB transmission, including urban–rural migration. Further research should focus on characterizing the contribution of these drivers to overall XDR-TB transmission in KwaZulu-Natal to inform design of targeted strategies to curb the drug-resistant TB epidemic.Grants from the US National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH): R01AI089349 (PI Gandhi and R01AI087465 (PI Gandhi). It was also supported in part by NIH/NIAID grants: K23AI083088 (PI Brust), K24AI114444 (PI Gandhi), K23AI134182 (PI Auld), Emory CFAR P30AI050409 (PI Curran), Einstein CFAR P30AI051519 (PI Goldstein), by Einstein/Montefiore ICTR UL1 TR001073 (PI Shamoon).https://academic.oup.com/jid2019-12-15hj2019Medical Microbiolog

Incidence, clinical spectrum, risk factors and impact of HIV-associated immune reconstitution inflammatory syndrome in South Africa.

Immune reconstitution inflammatory syndrome (IRIS) is a widely recognised complication of antiretroviral therapy (ART), but there are still limited data from resource-limited settings. Our objective was to characterize the incidence, clinical spectrum, risk factors and contribution to mortality of IRIS in two urban ART clinics in South Africa

Real-time polymerase chain reaction optimised for hepatitis C virus detection in dried blood spots from HIV-exposed infants, KwaZulu-Natal, South Africa

Background: There is a paucity of data on the prevalence of hepatitis C virus (HCV) in children, particularly in sub-Saharan Africa. A major obstacle in resource-limited settings for polymerase chain reaction (PCR) testing is the necessity for specimen transportation and storage at low temperatures. There are numerous recent studies of using real-time HCV PCR for diagnosis and screening of plasma and serum, but few have looked at using dried blood spot (DBS) specimens. Objectives: The aim of this study was to optimise a real-time HCV PCR method to detect HCV RNA from infant DBS specimens for use as a tool for HCV surveillance in KwaZulu-Natal, South Africa. Method: The LightCycler® 2.0 instrument was used for the HCV PCR using the LightCycler® RNA Master SYBR Green I kit. Template volume, primer concentration and primer annealing temperatures were optimised and the method was used on 179 DBS specimens from HIV-exposed infants in KwaZulu-Natal. Results: Primer concentrations adjusted to 0.25 µM and a template volume of 10 µL improved the PCR amplification. Primer annealing temperatures lowered from 65 °C to 58 °C resulted in higher quantities of amplified PCR product. The limit of detection of the optimised HCV PCR assay was between 1200 IU/mL and 3580 IU/mL of HCV RNA. HCV was not detected in any of the 179 DBS specimens. Conclusion: The optimised real-time HCV PCR on infant DBS specimens performed well, but HCV was not found in this surveillance study. HIV infection may have little impact on the vertical transmission of HCV in this region

A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission

Although the rates of vertical transmission of HIV in the developing world have improved to around 3% in countries like South Africa, resistance to antiretrovirals (ARV) used in Prevention of Mother-to-Child transmission (pMTCT) strategies may thwart such outcomes and affect the efficacy of future ARV regimens in mothers and children. This study conducted in Durban, South Africa, between 2010 and 2013 found a high rate of nevirapine (NVP) resistance among women receiving Zidovudine (AZT) from 14 weeks gestation, single dose nevirapine (sd NVP) at the onset of labor and a single dose of coformulated Tenofovir/Emtricitabine (TDF/FTC) postpartum. Using Sanger sequencing, high and intermediate levels of nevirapine (NVP) resistance were detected in 15/44 (34%) and in 1/44 (2%) of women tested, respectively. Most subjects selected the K103N mutation (22% (10/45) of all patients and 66% (10/15) of those with high-level NVP resistance). Such rate of NVP resistance is comparable to studies where only sd NVP was used. In conclusion, a post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum sd NVP to prevent mother-to-child HIV-1 transmission. J. Med. Virol. 87:1662-1667, 2015. © 2015 The Authors. Journal of Medical Virology published by Wiley Periodicals, Inc