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1.
PLOS Glob Public Health ; 4(5): e0003224, 2024.
Article in English | MEDLINE | ID: mdl-38805477

ABSTRACT

South Africa rolled out dolutegravir (DTG) as first-line antiretroviral therapy (ART) in December 2019 to overcome high rates of pretreatment non-nucleoside reverse transcriptase inhibitor drug resistance. In the context of transition to DTG-based ART, this study spatiotemporally analysed detectable HIV viral loads (VLs) prior to- and following DTG rollout in public-sector healthcare facilities in KwaZulu-Natal (KZN) province, the epicentre of the HIV epidemic in South Africa. We retrospectively curated a HIV VL database using de-identified routine VL data obtained from the National Health Laboratory Service for the period January 2018 to June 2022. We analysed trends in HIV viraemia and mapped median log10 HIV VLs per facility on inverse distance weighted interpolation maps. We used Getis-Ord Gi* hotspot analysis to identify geospatial HIV hotspots. We obtained 7,639,978 HIV VL records from 736 healthcare facilities across KZN, of which 1,031,171 (13.5%) had detectable VLs (i.e., VLs ≥400 copies/millilitre (mL)). Of those with detectable VLs, we observed an overall decrease in HIV VLs between 2018 and 2022 (median 4.093 log10 copies/mL; 95% confidence interval (CI) 4.087-4.100 to median 3.563 log10 copies/mL; CI 3.553-3.572), p<0.01 (median test). The downward trend in proportion of HIV VLs ≥1000 copies/mL over time was accompanied by an inverse upward trend in the proportion of HIV VLs between 400 and 999 copies/mL. Moreover, specific coastal and northern districts of KZN had persistently higher VLs, with emergent hotspots demonstrating spatial clustering of high median log10 HIV VLs. The overall decrease in HIV VLs over time shows good progress towards achieving UNAIDS 95-95-95 targets in KZN, South Africa. The DTG-transition has been associated with a reduction in VLs, however, there is a need for pre-emptive monitoring of low-level viraemia. Furthermore, our findings highlight that specific districts will need intensified HIV care despite DTG rollout.

2.
Afr J Lab Med ; 12(1): 2065, 2023.
Article in English | MEDLINE | ID: mdl-37434993

ABSTRACT

Background: KwaZulu-Natal ranked second highest among South African provinces for the number of laboratory-confirmed cases during the second wave of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The seroprevalence of SARS-CoV-2 among certain vulnerable groups, such as people living with HIV in KwaZulu-Natal, is unknown. Objective: The study aimed to determine the prevalence of SARS-CoV-2 immunoglobulin G (IgG) in HIV-positive versus HIV-negative patients. Methods: This was a retrospective analysis of residual clinical blood specimens unrelated to coronavirus disease 2019 (COVID-19) submitted for diagnostic testing at Inkosi Albert Luthuli Central Hospital, Durban, from 10 November 2020 to 09 February 2021. Specimens were tested for SARS-CoV-2 immunoglobulin G on the Abbott Architect analyser. Results: A total of 1977/8829 (22.4%) specimens were positive for SARS-CoV-2 antibodies. Seroprevalence varied between health districts from 16.4% to 37.3%, and was 19% in HIV-positive and 35.3% in HIV-negative specimens. Seroprevalence was higher among female patients (23.6% vs 19.8%; p < 0.0001) and increased with increasing age, with a statistically significant difference between the farthest age groups (< 10 years and > 79 years; p < 0.0001). The seroprevalence increased from 17% on 10 November 2020 to 43% on 09 February 2021 during the second wave. Conclusion: Our results highlight that during the second COVID-19 wave in KwaZulu-Natal a large proportion of people living with HIV were still immunologically susceptible. The reduced seropositivity in people with virological failure further emphasises the importance of targeted vaccination and vaccine response monitoring in these individuals. What the study adds: This study contributes to data on SARS-CoV-2 seroprevalence before and during the second wave in KwaZulu-Natal, South Africa, which has the highest HIV prevalence globally. Reduced seropositivity was found among people living with HIV with virological failure, highlighting the importance of targeted booster vaccination and vaccine response monitoring.

3.
Viruses ; 14(5)2022 04 21.
Article in English | MEDLINE | ID: mdl-35632596

ABSTRACT

Human cytomegalovirus (HCMV) can cause significant end-organ diseases such as pneumonia in HIV-exposed infants. Complex viral factors may influence pathogenesis including: a large genome with a sizeable coding capacity, numerous gene regions of hypervariability, multiple-strain infections, and tissue compartmentalization of strains. We used a whole genome sequencing approach to assess the complexity of infection by comparing high-throughput sequencing data obtained from respiratory and blood specimens of HIV-exposed infants with severe HCMV pneumonia with those of lung transplant recipients and patients with hematological disorders. There were significantly more specimens from HIV-exposed infants showing multiple HCMV strain infection. Some genotypes, such as UL73 G4B and UL74 G4, were significantly more prevalent in HIV-exposed infants with severe HCMV pneumonia. Some genotypes were predominant in the respiratory specimens of several patients. However, the predominance was not statistically significant, precluding firm conclusions on anatomical compartmentalization in the lung.


Subject(s)
Cytomegalovirus Infections , HIV Infections , Pneumonia , Cytomegalovirus/genetics , Cytomegalovirus Infections/epidemiology , HIV Infections/complications , Humans , Infant , South Africa/epidemiology
4.
Viruses ; 14(4)2022 04 10.
Article in English | MEDLINE | ID: mdl-35458518

ABSTRACT

To understand the problem of persistent Hepatitis B virus (HBV) viraemia in HIV/HBV co-infected patients on HBV-active antiretroviral therapy (ART), we assessed the rate of HBV virological response in patients on HBV-active ART in KwaZulu-Natal, South Africa, and analysed factors associated with persistent HBV viraemia. One hundred and fifty eligible participants with a chronic HBV diagnosis, with or without HIV coinfection, were enrolled and followed up after 6 months. The HBV pol gene was sequenced by next-generation sequencing and mutations were determined using the Stanford HBVseq database. Logistic regression analysis was used to assess factors associated with HBV viraemia at 6-month follow-up. The mean duration of HBV-active ART was 24 months. Thirty-seven of one hundred and six (35%) participants receiving HBV-active ART for longer than 6 months had virological failure. Advanced immunosuppression with CD4+ cell counts <200 cells/µL was independently associated with persistent HBV viraemia, aOR 5.276 (95% CI 1.575−17.670) p = 0.007. A high proportion of patients on HBV-active ART are unsuppressed, which will ultimately have an impact on global elimination goals. Better monitoring should be implemented, especially in HIV-coinfected patients with low CD4+ cell counts and followed by early HBV drug-resistance testing.


Subject(s)
Coinfection , HIV Infections , Hepatitis B virus , Hepatitis B , Viral Replicase Complex Proteins , Viremia , Antiretroviral Therapy, Highly Active/adverse effects , CD4 Lymphocyte Count , DNA, Viral/genetics , HIV Infections/complications , HIV Infections/drug therapy , Hepatitis B virus/genetics , Humans , Mutation , South Africa/epidemiology , Viral Load , Viral Replicase Complex Proteins/genetics , Viremia/genetics
5.
J Glob Antimicrob Resist ; 29: 468-475, 2022 06.
Article in English | MEDLINE | ID: mdl-34785393

ABSTRACT

OBJECTIVES: In low-middle-income countries, increasing levels of HIV drug resistance (HIVDR) on second-line protease inhibitor (PI)-based regimens are a cause for concern given the limited drug options for third-line antiretroviral therapy (ART). We conducted a retrospective analysis of routine HIV-1 genotyping laboratory data from KwaZulu-Natal, South Africa, to describe the frequency and patterns of HIVDR mutations and their consequent impact on standardised third-line regimens. METHODS: This was a cross-sectional analysis of all HIV-1 genotypic resistance tests conducted by the National Health Laboratory Service in KwaZulu-Natal (January 2015 to December 2016) for adults and adolescents (age ≥10 years) on second-line PI-based ART with virological failure. We assigned a third-line regimen to each record based on a national treatment algorithm and calculated the genotypic susceptibility score (GSS) for that regimen. RESULTS: Of 348 samples analysed, 287 (82.5%) had at least one drug resistance mutation (DRM) and 114 (32.8%) had at least one major PI DRM. Major PI resistance was associated with longer duration on second-line ART (aOR per 6-months = 1.11, 95% CI 1.04-1.19) and older age (aOR = 1.03, 95% CI 1.01-1.05). Of 112 patients requiring third-line ART, 12 (10.7%) had a GSS of <2 for the algorithm-assigned third-line regimen. CONCLUSION: One-third of people failing second-line ART had significant PI DRMs. A subgroup of these individuals had extensive HIVDR, where the predicted activity of third-line ART was suboptimal, highlighting the need for continuous evaluation of outcomes on third-line regimens and close monitoring for emergent HIV-1 integrase inhibitor resistance.


Subject(s)
Anti-HIV Agents , HIV Infections , HIV-1 , Adolescent , Adult , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Child , Cross-Sectional Studies , Drug Resistance, Viral/genetics , HIV Infections/drug therapy , HIV-1/genetics , Humans , Protease Inhibitors/pharmacology , Retrospective Studies , South Africa
6.
Future Microbiol ; 16: 1401-1414, 2021 12.
Article in English | MEDLINE | ID: mdl-34812046

ABSTRACT

Cytomegalovirus pneumonia has repeatedly been described in the context of HIV-exposed uninfected and HIV-infected infants. Despite its significant role in the etiology of childhood pneumonia, there is still a paucity of literature generally, and specifically in Africa, suggesting that it might be a neglected disease. Emerging evidence highlights the importance of postnatal transmission through breastmilk. The pathogenetic significance of the multiplicity of strains acquired through repeated re-infections in early infancy is unknown. The development of cheap, accurate diagnostic tools and safe, effective antivirals and the maintenance of effective prevention and treatment of pediatric HIV are needed to manage cytomegalovirus pneumonia in low-resource settings.


Subject(s)
Cytomegalovirus Infections , HIV Infections , Pneumonia , Africa/epidemiology , Child , Cytomegalovirus , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/epidemiology , HIV Infections/complications , HIV Infections/epidemiology , Humans , Infant , Infectious Disease Transmission, Vertical/prevention & control
7.
BMC Infect Dis ; 20(1): 847, 2020 Nov 16.
Article in English | MEDLINE | ID: mdl-33198649

ABSTRACT

BACKGROUND: Hepatitis B virus (HBV), Human Immunodeficiency virus (HIV) and Tuberculosis (TB) are common infections in South Africa. We utilized the opportunity of care provision for HIV-TB co-infected patients to better understand the relationship between these coinfections, determine the magnitude of the problem, and identify risk factors for HBV infection in HIV infected patients with and without TB in KwaZulu-Natal, South Africa. METHODS: This retrospective cohort analysis was undertaken in 2018. In-care HIV infected patients were included in the analysis. Results from clinical records were analysed to determine the prevalence, incidence, persistence and factors associated with HBsAg positivity in HIV-infected patients with or without TB co-infection. RESULTS: A total of 4292 HIV-infected patients with a mean age of 34.7 years (SD: 8.8) were included. Based on HBsAg positivity, the prevalence of HBV was 8.5% (363/4292) [95% confidence interval (CI): 7.7-9.3] at baseline and 9.4% (95%CI: 8.6-10.3%) at end of follow-up. The HBV incidence rate was 2.1/100 person-years (p-y). Risk of incident HBV infection was two-fold higher among male patients (HR 2.11; 95% CI: 1.14-3.92), while severe immunosuppression was associated with a greater than two-fold higher risk of persistent infection (adjusted risk ratio (RR) 2.54; 95% CI 1.06-6.14; p = 0.004. Additionally, active TB at enrolment was associated with a two-fold higher risk of incident HBV infection (aHR 2.38; 95% CI: 0.77-7.35). CONCLUSION: The provision of HIV care and treatment in high HBV burden settings provide a missed opportunity for HBV screening, immunization and care provision.


Subject(s)
AIDS-Related Opportunistic Infections/epidemiology , Coinfection/epidemiology , HIV , Hepatitis B virus/immunology , Hepatitis B/diagnosis , Hepatitis B/epidemiology , Mycobacterium tuberculosis/isolation & purification , Tuberculosis/epidemiology , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/drug therapy , AIDS-Related Opportunistic Infections/virology , Adult , Anti-HIV Agents/therapeutic use , Coinfection/virology , Female , Follow-Up Studies , Hepatitis B/virology , Hepatitis B Surface Antigens/immunology , Humans , Incidence , Male , Prevalence , Retrospective Studies , Risk Factors , South Africa/epidemiology , Tuberculosis/diagnosis , Tuberculosis/microbiology , Young Adult
8.
BMC Public Health ; 19(1): 731, 2019 Jun 11.
Article in English | MEDLINE | ID: mdl-31185962

ABSTRACT

BACKGROUND: With Universal Health Coverage and Integrated People-centred Health Care, streamlined health-systems and respectful care are necessary. South Africa has made great strides in prevention of mother-to-child transmission (PMTCT) but with the great burden of HIV, a minimum of birth and 10-week HIV-PCR testing are required for the estimated 360,000 HIV-exposed infants born annually which presents many challenges including delayed results and loss to follow-up. Point-of-care (POC) HIV testing of infants addresses these challenges well and facilitates initiation of HIV-infected infants rapidly after diagnosis for best clinical outcomes. METHODS: Objectives were to determine accuracy, feasibility and acceptability of POC testing compared to standard-of-care (SOC) central-laboratory testing. HIV-exposed infants for birth PCR testing in hospital (n = 323) and follow-up at a primary health care clinic (n = 117) in Durban, South Africa were included. A baseline situational-analysis reviewed registers and phoned mothers of HIV-exposed infants prior to the intervention. An effectiveness-implementation study of the Alere™q HIV-1/2 Detect POC test (heel-prick specimen processed in 50 min) was compared with SOC with questionnaires to mothers and staff. Stata 14 was used for analysis. RESULTS: At baseline 2% of birth HIV tests were missed; only 40% of mothers could be contacted; 17% did not receive birth test result; 19% did not have a 10-week test; 39% had not received the 10-week results. There were 5(1.5%) HIV-infected and 318(98.5%) HIV-negative infants detected in hospital with all clinic babies negative. All positive infants commenced ART before discharge. Ultimately POC and SOC had perfect concordance but for 10 SOC tests researchers actively tracked-down results or repeated tests. Turn around times for SOC tests were on average 8-days (IQR 6-10 days) and for POC testing was 0-days. The POC error-rate was 9,6% with all giving a result when repeated. The majority of mothers (92%) preferred POC testing with 7% having no preference. No staff preferred SOC testing with 79% preferring POC and 21% having no preference. CONCLUSIONS: Point-of-care HIV testing for EID is accurate, feasible and acceptable, with benefits of early ART for all positive infants at birth facilities. We recommend that it be considered best practice for EID. TRIAL REGISTRATION: ISRCTN38911104 registered 9 January 2018 - retrospectively registered.


Subject(s)
HIV Infections/diagnosis , HIV , Health Plan Implementation , Neonatal Screening/methods , Point-of-Care Systems , Early Diagnosis , Female , HIV Infections/prevention & control , HIV Infections/transmission , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Male , Polymerase Chain Reaction/methods , Pregnancy , Retrospective Studies , South Africa
9.
Pediatr Infect Dis J ; 38(7): e138-e142, 2019 07.
Article in English | MEDLINE | ID: mdl-31192977

ABSTRACT

BACKGROUND: South African early infant diagnosis guidelines shifted to recommending an initial HIV nucleic acid-based test (NAT) test at birth in 2015. Prior to this, initial NAT was recommended at 6 weeks of age. Here we examine parameters of early infant diagnosis performance in KwaZulu-Natal before and after this change. METHODS: Data on all HIV diagnostic NAT conducted for the province between January 2013 and April 2016 were assembled and analyzed. Laboratory barcodes allowed identification of repeat tests on the same child. We evaluated coverage, positivity rates, age at testing and frequency of repeat tests across birth cohorts. RESULTS: In birth cohorts 2013 and 2014, 62.1% and 61.8%, respectively, of tests <16 weeks were done in children who were 6-8 weeks of age. In birth cohort 2015, 41.3% of tests <16 weeks were done earlier at <2 weeks of age. The percentage of children with a positive result who had at least 1 follow-up test increased from 11.5% and 13.1% in birth cohorts 2013 and 2014, respectively, to 24.8% in 2015. The percentage of infants with an initial nonpositive result who received at least 1 follow-up test did not appreciably change from 15.0% and 14.4% in 2013 and 2014, respectively, to 14.7% in 2015. CONCLUSIONS: Birth testing allows for earlier identification of HIV-infected infants who need urgent antiretroviral treatment initiation. Although follow-up testing rates may be underestimated in this data source, repeat testing rates remained low. More effort is needed to ensure infants tested at birth continue to be engaged in care and undergo follow-up testing.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Diagnostic Tests, Routine/methods , Early Diagnosis , HIV Infections/diagnosis , HIV Infections/drug therapy , Female , Humans , Infant , Infant, Newborn , Male , Molecular Diagnostic Techniques/methods , South Africa , Treatment Outcome
10.
J Med Virol ; 89(6): 1080-1087, 2017 06.
Article in English | MEDLINE | ID: mdl-27918839

ABSTRACT

Cytomegalovirus (CMV) pneumonitis is a significant cause of morbidity and mortality of children in Africa. The current practice for diagnosing CMV pneumonitis in this setting is based on interpretation of clinical, laboratory, and radiological findings. There is a need for a sensitive and specific laboratory test to objectively distinguish between patients with CMV pneumonitis and those with CMV infection, and non-CMV pneumonia. In this study, we compared plasma and non-bronchoscopic bronchoalveolar lavage (NBBAL) CMV viral loads in patients with CMV pneumonitis and those with CMV infection and non-CMV pneumonia. Receiver operator characteristic curve analysis was used to establish a threshold and assess utility of viral loads in the diagnosis of CMV pneumonitis. We assessed the urea dilution method, and expression of viral loads relative to the total amount of extracted nucleic acids in correcting for NBBAL dilution. CMV quantification in NBBAL specimens was more predictive of CMV pneumonitis than blood CMV quantification. The threshold of 4.03 log IU/ml in NBBAL specimens has good predictive value and can be used to guide management of infants with suspected CMV pneumonitis. Adjusting for dilution of NBBAL specimens by using the urea dilution method or by expressing the viral load relative to the total nucleic acids extracted did not provide additional analytical benefits. J. Med. Virol. 89:1080-1087, 2017. © 2016 Wiley Periodicals, Inc.


Subject(s)
Bronchoalveolar Lavage Fluid/virology , Cytomegalovirus Infections/diagnosis , Cytomegalovirus/isolation & purification , Pneumonia/diagnosis , Viral Load , Blood/virology , Female , Humans , Infant , Male , Predictive Value of Tests , ROC Curve
11.
Afr J Lab Med ; 5(1): 349, 2016.
Article in English | MEDLINE | ID: mdl-28879108

ABSTRACT

BACKGROUND: Poor quality dried blood spot (DBS) specimens are usually rejected by virology laboratories, affecting early infant diagnosis of HIV. The practice of combining two incompletely-filled DBS in one specimen preparation tube during pre-analytical specimen processing (i.e., the two-spot method) has been implemented to reduce the number of specimens being rejected for insufficient volume. OBJECTIVES: This study analysed laboratory data to describe the quality of DBS specimens and the use of the two-spot method over a one-year period, then validated the two-spot method against the standard (one-spot) method. METHODS: Data on HIV-1 PCR test requests submitted in 2014 to the Department of Virology at Inkosi Albert Luthuli Central Hospital in KwaZulu-Natal province, South Africa were analysed to describe reasons for specimen rejection, as well as results of the two-spot method. The accuracy, lower limit of detection and precision of the two-spot method were assessed. RESULTS: Of the 88 481 specimens received, 3.7% were rejected for pre-analytical problems. Of those, 48.9% were rejected as a result of insufficient specimen volume. Two health facilities had significantly more specimen rejections than other facilities. The two-spot method prevented 10 504 specimen rejections. The Pearson correlation coefficient comparing the standard to the two-spot method was 0.997. CONCLUSIONS: The two-spot method was comparable with the standard method of pre-analytical specimen processing. Two health facilities were identified for targeted retraining on specimen quality. The two-spot method of DBS specimen processing can be used as an adjunct to retraining, to reduce the number of specimens rejected and improve linkage to care.

12.
Afr. j. lab. med. (Online) ; 5(1): 1-6, 2016. ilus
Article in English | AIM (Africa) | ID: biblio-1257312

ABSTRACT

Background: Poor quality dried blood spot (DBS) specimens are usually rejected by virology laboratories; affecting early infant diagnosis of HIV. The practice of combining two incompletely-filled DBS in one specimen preparation tube during pre-analytical specimen processing (i.e.; the two-spot method) has been implemented to reduce the number of specimens being rejected for insufficient volume.Objectives: This study analysed laboratory data to describe the quality of DBS specimens and the use of the two-spot method over a one-year period; then validated the two-spot method against the standard (one-spot) method.Methods: Data on HIV-1 PCR test requests submitted in 2014 to the Department of Virology at Inkosi Albert Luthuli Central Hospital in KwaZulu-Natal province; South Africa were analysed to describe reasons for specimen rejection; as well as results of the two-spot method. The accuracy; lower limit of detection and precision of the two-spot method were assessed.Results: Of the 88 481 specimens received; 3.7% were rejected for pre-analytical problems. Of those; 48.9% were rejected as a result of insufficient specimen volume. Two health facilities had significantly more specimen rejections than other facilities. The two-spot method prevented 10 504 specimen rejections. The Pearson correlation coefficient comparing the standard to the two-spot method was 0.997.Conclusions: The two-spot method was comparable with the standard method of pre-analytical specimen processing. Two health facilities were identified for targeted retraining on specimen quality. The two-spot method of DBS specimen processing can be used as an adjunct to retraining; to reduce the number of specimens rejected and improve linkage to care


Subject(s)
HIV-1 , Dried Blood Spot Testing , Polymerase Chain Reaction , South Africa , Specimen Handling
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