Resistance is common in paediatric patients failing ART in South Africa.

Background: Minimal data exist on HIV drug resistance patterns and prevalence among paediatric patients failing ART in resource-limited settings. We assessed levels of HIV drug resistance in children with virological failure.

Methods: This cross-sectional study, performed from March 2017 to March 2019 in South Africa, enrolled HIV-positive children aged ≤19 years, receiving ART through public health facilities with recent evidence suggestive of virological failure (at least one viral load ≥1000 copies/mL), across 45 randomly selected high-volume clinics from all nine provinces.

Pretreatment Human Immunodeficiency Virus (HIV) Drug Resistance Among Treatment-Naive Infants Newly Diagnosed With HIV in 2016 in Namibia: Results of a Nationally Representative Study.

Background: The World Health Organization (WHO) recommends routine surveillance of pretreatment human immunodeficiency virus (HIV) drug resistance (HIVDR) in children <18 months of age diagnosed with HIV through early infant diagnosis (EID). In 2016, 262 children <18 months of age were diagnosed with HIV in Namibia through EID. Levels of HIVDR in this population are unknown.

Epidemiology of SARS-CoV-2 infection and SARS-CoV-2 positive hospital admissions among children in South Africa.

Introduction: We describe epidemiology and outcomes of confirmed SARS-CoV-2 infection and positive admissions among children <18 years in South Africa, an upper-middle income setting with high inequality.

Methods: Laboratory and hospital COVID-19 surveillance data, 28 January - 19 September 2020 was used. Testing rates were calculated as number of tested for SARS-CoV-2 divided by population at risk; test positivity rates were calculated as positive tests divided by total number of tests.

Community-led cross-sectional study of social and employment circumstances, HIV and associated factors amongst female sex workers in South Africa: study protocol.

Background: In South Africa, female sex workers (FSWs) are perceived to play a pivotal role in the country's HIV epidemic. Understanding their health status and risk factors for adverse health outcomes is foundational for developing evidence-based health care for this population.

Objective: Describe the methodology used to successfully implement a community-led study of social and employment circumstances, HIV and associated factors amongst FSWs in South Africa.

Estimating the contribution of key populations towards HIV transmission in South Africa.

Introduction: In generalized epidemic settings, there is insufficient understanding of how the unmet HIV prevention and treatment needs of key populations (KPs), such as female sex workers (FSWs) and men who have sex with men (MSM), contribute to HIV transmission. In such settings, it is typically assumed that HIV transmission is driven by the general population. We estimated the contribution of commercial sex, sex between men, and other heterosexual partnerships to HIV transmission in South Africa (SA).

HIV drug resistance profile in South Africa: Findings and implications from the 2017 national HIV household survey.

Background: HIV drug resistance (HIVDR) testing was included in the 2017 South African national HIV household survey. We describe the prevalence of HIVDR by drug class, age, sex and antiretroviral drugs (ARV) status.

Methods: Dried blood were spots tested for HIV, with Viral load (VL), exposure to ARVs and HIVDR testing among those HIV positive.

Multi-Laboratory Comparison of Next-Generation to Sanger-Based Sequencing for HIV-1 Drug Resistance Genotyping.

Next-generation sequencing (NGS) is increasingly used for HIV-1 drug resistance genotyping. NGS methods have the potential for a more sensitive detection of low-abundance variants (LAV) compared to standard Sanger sequencing (SS) methods. A standardized threshold for reporting LAV that generates data comparable to those derived from SS is needed to allow for the comparability of data from laboratories using NGS and SS.

High levels of resistance to nucleoside/nucleotide reverse transcriptase inhibitors in newly diagnosed antiretroviral treatment-naive children in sub-Saharan Africa.

: Exposure of infants to antiretroviral drugs for prevention of mother-to-child transmission can induce resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). Data from nine national surveys of pretreatment drug resistance in children newly diagnosed with HIV show high levels of resistance to NRTIs included in first-line antiretroviral treatment (ART) regimens (dual abacavir-lamivudine/emtricitabine resistance). Additional research is needed to determine the impact of NRTI resistance on treatment response and optimize infant ART.

The role of drug resistance in poor viral suppression in rural South Africa: findings from a population-based study.

Background: Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa.

Methods: We conducted HIV drug resistance genotyping and ART analyte testing on dried blood spots (DBS) from HIV-positive adults participating in a 2014 survey in North West Province.

Low-Abundance Drug-Resistant HIV-1 Variants in Antiretroviral Drug-Naive Individuals: A Systematic Review of Detection Methods, Prevalence, and Clinical Impact.

Background: The presence of high-abundance drug-resistant HIV-1 jeopardizes success of antiretroviral therapy (ART). Despite numerous investigations, the clinical impact of low-abundance drug-resistant HIV-1 variants (LA-DRVs) at levels <15%-25% of the virus population in antiretroviral (ARV) drug-naive individuals remains controversial.

Methods: We systematically reviewed 103 studies assessing prevalence, detection methods, technical and clinical detection cutoffs, and clinical significance of LA-DRVs in antiretroviral drug-naive adults.

Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4-8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011-12 and 2012-13.

Background: South Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT).

HIV diagnostic challenges in breast-fed infants of mothers on antiretroviral therapy.

Background: Prompt initiation of antiretroviral therapy (ART) for HIV-infected infants is strongly recommended but diagnostic confirmation is important as committing children to life-long ART carries serious health and social implications.

Methods: Two HIV-exposed infants in Johannesburg, South Africa were identified presenting with unusual trajectories of diagnostic nucleic acid amplification tests (NAAT) and viral load results.

Results: Case 1 had repeat indeterminate NAAT results during the first 3 weeks of life; repeat testing thereafter was negative with undetectable viral load including after daily nevirapine prophylaxis ended.

Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000-2016: A Pooled Sequence Analysis.

Background: South Africa has the largest public antiretroviral therapy (ART) programme in the world. We assessed temporal trends in pretreatment HIV-1 drug resistance (PDR) in ART-naïve adults from South Africa.

Methods: We included datasets from studies conducted between 2000 and 2016, with HIV-1 sequences from more than ten ART-naïve adults.

Low Frequency of Protease Inhibitor Resistance Mutations and Insertions in HIV-1 Subtype C Protease Inhibitor-Naïve Sequences.

Human immunodeficiency virus-1 (HIV-1) protease sequences from 2,225 protease inhibitor (PI)-naïve HIV-1 subtype C-infected individuals collected over a 14-year period were analyzed for polymorphisms. Over 50% of sequences differed from an HIV-1 subtype B consensus sequence at 8 of the 99 amino acids at residues 12, 15, 19, 36, 41, 69, 89, and 93, but not in the functionally important regions. The frequency of primary resistance and accessory mutations occurred in <1% of the sequences.

Provincial and national prevalence estimates of transmitted HIV-1 drug resistance in South Africa measured using two WHO-recommended methods.

Background: Sentinel surveillance of transmitted HIV drug resistance (TDR) among recently infected populations within a country was recommended by the World Health Organization from 2004 to 2015.

Methods: Serum specimens collected as part of the 2010, 2011 and 2012 National Antenatal Sentinel HIV Prevalence Surveys were used to estimate provincial and national TDR prevalence in South Africa.

Results: Moderate (5-15%) levels of transmitted non-nucleoside reverse transcriptase inhibitor (NNRTI) drug class resistance were detected in three of five provinces surveyed in 2010 and 2011 (Eastern Cape, Free State and KwaZulu-Natal).

Walking and living independently with spina bifida: a 50-year prospective cohort study.

Aim: To describe trends in walking and living independently in a cohort of consecutive cases of spina bifida, followed-up over 50 years.

Method: From 1972 to 2017, a cohort of 117 (born 1963-1971, 50 males, 67 females) survivors and/or carers was surveyed approximately every 5 years by clinical examination and/or postal questionnaire/telephone interview. The Office for National Statistics provided details of deaths.

Moderate-to-High Levels of Pretreatment HIV Drug Resistance in KwaZulu-Natal Province, South Africa.

There is evidence of increasing levels of pretreatment HIV drug resistance (PDR) in Southern Africa. We used data from two large population-based HIV surveillance studies to estimate prevalence of PDR in KwaZulu-Natal, the province with the highest HIV prevalence in South Africa. Sanger sequencing was performed on samples obtained from a longitudinal HIV surveillance program (study A, 2013-2014) and the HIV Incidence Provincial Surveillance System (study B, 2014-2015).

HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study.

Background: HIV drug resistance (HIVDR) poses a threat to future antiretroviral therapy success. Monitoring HIVDR patterns is of particular importance in populations such as sex workers (SWs), where documented HIV prevalence is between 34-89%, and in countries with limited therapeutic options. Currently in South Africa, there is a dearth in evidence and no ongoing surveillance of HIVDR amongst sex work populations.

HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis.

Background: Pretreatment drug resistance in people initiating or re-initiating antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) might compromise HIV control in low-income and middle-income countries (LMICs). We aimed to assess the scale of this problem and whether it is associated with the intiation or re-initiation of ART in people who have had previous exposure to antiretroviral drugs.

Methods: This study was a systematic review and meta-regression analysis.

Human Immunodeficiency Virus (HIV) Drug Resistance in African Infants and Young Children Newly Diagnosed With HIV: A Multicountry Analysis.

Background: Programs for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) have been scaled up in many low- and middle-income countries. However, HIV drug resistance (HIVDR) data among HIV-1-infected young children remain limited.

Methods: Surveys of pretreatment HIVDR among children aged <18 months who were diagnosed with HIV through early infant diagnosis were conducted in 5 sub-Saharan African countries (Mozambique, Swaziland, South Africa, Uganda, and Zimbabwe) between 2011 and 2014 following World Health Organization (WHO) guidance.

Rates of virological suppression and drug resistance in adult HIV-1-positive patients attending primary healthcare facilities in KwaZulu-Natal, South Africa.

Background: KwaZulu-Natal (KZN) Province in South Africa has the highest HIV disease burden in the country, with an estimated population prevalence of 24.7%. A pilot sentinel surveillance project was undertaken in KZN to classify the proportion of adult patients failing first-line ART and to describe the patterns of drug resistance mutations (DRMs) in patients with virological failure (VF).