Browsing by Author "Naidoo, Kogieleum."

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Addressing challenges in scaling up TB and HIV treatment integration in rural primary healthcare clinics in South Africa (SUTHI): a cluster randomized controlled trial protocol.
(Implementation Science., 2015) Naidoo, Kogieleum.; Gengiah, Santhanalakshmi.; Yende-Zuma, Fortunate Nonhlanhla.; Padayatchi, Nesri.; Barker, Pierre.; Nunn, Andrew.; Subrayen, Priashni.; Abdool Karim, Salim Safurdeen.
Abstract available in pdf.
Aetiology, clinical presentation, and outcome of meningitis in patients coinfected with human immunodeficiency virus and tuberculosis.
(Hindawi Publishing Corporation., 2011) Bhagwan, Smita.; Naidoo, Kogieleum.
We conducted a retrospective review of confirmed HIV-TB coinfected patients previously enrolled as part of the SAPiT study in Durban, South Africa. Patients with suspected meningitis were included in this case series. From 642 individuals, 14 episodes of meningitis in 10 patients were identified. For 8 patients, this episode of meningitis was the AIDS defining illness, with cryptococcus (9/14 episodes) and tuberculosis (3/14 episodes) as the commonest aetiological agents. The combination of headache and neck stiffness (78.6%) was the most frequent clinical presentation. Relapsing cryptococcal meningitis occurred in 3/7 patients.Mortality was 70% (7/10), with 4 deaths directly due to meningitis. In an HIV TB endemic region we identified cryptococcus followed by tuberculosis as the leading causes of meningitis. We highlight the occurrence of tuberculous meningitis in patients already receiving antituberculous therapy. The development of meningitis heralded poor outcomes, high mortality, and relapsing meningitis despite ART.
Assessing adherence to antiretroviral therapy in a rural paediatric cohort in KwaZulu-Natal, South Africa.
(Springer., 2016) Smith, Chanelle.; Gengiah, Tanuja Narayansamy.; Yende-Zuma, Fortunate Nonhlanhla.; Upfold, Michele.; Naidoo, Kogieleum.
Abstract available in pdf.
An audit of the standard of care received by HIV positive patients on ART at a community health centre in KZN.
(2013) Inderjeeth, Nishana.; Naidoo, Kogieleum.
Introduction: South Africa has the highest number of HIV infected individuals in the world.2 The South African government has established National treatment guidelines for HIV positive patients to help ensure quality of care. The success of these guidelines depends on the commitment and level of adherence to them by hospitals and clinics. Aim: A descriptive study evaluating the standard of care received by HIV positive patients was undertaken at a community health centre in KwaDabeka, a semi-urban town in Kwa-Zulu Natal. This was benchmarked against the National ART Guidelines for 2010, which was the national policy at the time this study was undertaken. The objectives were to identify any deficiencies in the care of patients with HIV/AIDS, and to suggest possible solutions as well as to identify a demographic profile of the patients accessing care. Methods: The researcher selected three hundred and sixty patient files using a random process and then analyzed them. This sample size was calculated using a confidence interval of 95% of a total number of six thousand patients. Adult patients using ART for the period of 01 January 2011 until 31 December 2011 were only included. Pregnant patients and children were excluded from the study .The variables analyzed were generated using the pre-initiation, initiation and monitoring recommendations of the National ART Guidelines of 2010. A data sheet was drawn-up consisting of the various variables. This was analyzed using SPSS version 21. Simple descriptive statistics, univariate analysis, and frequency distribution tables were used to analyze the data. Tables, pie charts, and graphs have been used to represent the analyzed data. Results: Females comprised 65% and the mean patient age was 39 years. While the overall patient management was in accordance to the guidelines, there were major areas of con- compliance. These included the more than 80% of patients who did not have: pap smears; nutritional assessments; follow-up Tuberculosis (TB) symptom reviews; and mental health evaluations. In addition, there was a significant delay from obtaining a CD4 count to initiation of therapy of two months or longer in more than 50% of patients. Furthermore, the clinic did not comply with fast –tracking 84.5% of patients who needed to be initiated within two weeks of obtaining a CD4 count. Adverse events due to antiretroviral therapy were reported in approximately 41% of the patients, however, 25% did not have their regimen changed despite having a serious adverse event documented. The incidence of concurrent infection with TB was 32%, however none of the remaining non-infected patients (68%), received Isoniazid prophylaxis. Recommendations: The management of KwaDabeka CHC have significant challenges to overcome in order to optimise their treatment of HIV positive patients. Possible solutions must include access to the National ART Guidelines for all relevant health-care workers, regular medical update programmes on the management of HIV positive patients, and improving resources and relevant procedural skills.
Challenges in the integration of TB and HIV care : evidence for improving patient management and health care policy.
(2016) Naidoo, Kogieleum.; Abdool Karim, Salim Safurdeen.
TB infection remains a leading cause of morbidity and mortality among patients with HIV infection, while HIV is the strongest risk factor for development of active TB. Integration of HIV and TB treatment is key to reducing mortality in co-infected patients; but many obstacles stand in the way of effective scale-up of this approach to HIV-TB treatment. The challenges associated with HIV-TB integration extend from clinical complexities in individual patient management, to impediments in health service organization and prioritization to address this urgent public health priority, especially in sub-Saharan Africa where TB-HIV co-infection rates reach 80%. The purpose of this study was to assess and identify strategies to overcome the challenges in immune reconstitution and drug safety/tolerability when integrating HIV and TB care in a cost-effective manner to reduce co-infection mortality. Clinical and operational service data from the Starting Antiretroviral therapy at three Points in Tuberculosis Treatment (SAPiT – CAPRISA 003) study, a 3-arm, randomized control trial in 642 newly diagnosed sputum smear-positive TB-HIV co-infected adult patients with screening CD4+ cell count < 500 cells/mm3, were analysed. In addition, the incidence rate of unmasked clinical TB following ART initiation was assessed through a retrospective chart review conducted in HIV infected patients enrolled at the rural CAPRISA AIDS Treatment Programme. Overall, mortality was 56% lower (RR=0.44; 95% CI: 0.25 to 0.79; P = 0.003) in patients initiated on ART during TB treatment compared to ART deferral to after TB treatment completion. However, the risk of immune reconstitution inflammatory syndrome (IRIS) was higher (incidence rate ratio (IRR), 2.6 (95% CI, 1.5 to 4.8); P < 0.001, in patients initiating ART within the first 2 months compared to later ART initiation during TB treatment. In the most severely immuno-compromised patients (CD4 counts <50 cells/mm3) early ART integration was associated with an almost five-fold increased risk of IRIS (IRR 4.7 (95% CI, 1.5 to 19.6); P = 0.004. Patients initiating ART in the first 2 months of TB therapy had higher hospitalization rates (42% vs. 14%; P = 0.007) and longer time to resolution (70.5 vs. 29.0 days; P = 0.001) than patients in the other two groups. When assessing available evidence, these results indicate that ART initiation in patients with CD4 cell counts >50 cells/mm3 would be most appropriate after completion of intensive phase of TB therapy, a strategy that was found to cost $1840 per patient treated. Among HIV infected patients initially screening negative for TB there was a fourfold higher incidence rate of unmasking TB in the first 3 months after ART initiation, compared to the subsequent 21 months post-ART initiation. The new information generated by this study provides important evidence for policy and clinical management of patients with HIV and TB co-infection. Firstly, careful clinical vigilance for ‘unmasked’ TB is required in patients initiating ART. Secondly, the survival benefit of AIDS therapy in TB patients can be maximized by initiating ART as soon as possible after TB therapy has been started in patients with advanced immunosuppression, i.e., those with CD4+ counts <50 cells/mm3. However, patients with higher CD4+ cell counts should delay ART initiation to at least 8 weeks after the start of TB therapy to minimize the incidence and duration of immune reconstitution disease and consequent hospitalization. Thirdly, this approach, which is at variance with current World Health Organization policy and guidelines, is cost-effective and readily implementable within the clinical setting. Finally, addressing the operational challenges to HIV-TB treatment integration can improve patient outcomes with substantial public health by reducing mortality by the most important causes of death in South Africa.
Changes to antiretroviral drug regimens during integrated TB-HIV treatment: results of the SAPiT trial.
(International Medical Press., 2014) Naidoo, Anushka.; Naidoo, Kogieleum.; Yende-Zuma, Fortunate Nonhlanhla.; Gengiah, Tanuja Narayansamy.; Padayatchi, Nesri.; Gray, Andrew Lofts.; Bamber, Sheila.; Nair, Gonasagrie.; Abdool Karim, Salim Safurdeen.
Background—Frequency of drug changes in combination antiretroviral therapy among patients starting both tuberculosis (TB) and human immunodeficiency virus (HIV) therapy, as a result of treatment-limiting toxicity or virological failure, is not well established. Methods—Patients in the Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) trial were randomized to initiate antiretroviral therapy either early or late during TB treatment or after completion of TB treatment. Drug changes due to toxicity (defined as due to grade 3 or 4 adverse events) or virological failure (defined as viral load > 1000 copies/ml on two occasions, taken at least 4 weeks apart) were assessed in these patients. Results—A total of 501 TB-HIV co-infected patients were followed for a mean of 16.0 (95% confidence interval (CI): 15.5 to 16.6) months after antiretroviral therapy (ART) initiation. The standard first-line ARVs used, were efavirenz, lamivudine and didanosine. Individual drug switches for toxicity occurred in 14 patients (incidence rate: 2.1 per 100 person-years; 95% (CI): 1.1 to 3.5), and complete regimen changes due to virological failure in 25 patients (incidence rate: 3.7 per 100 person-years; CI: 2.4 to 5.5). The most common treatment limiting toxicities were neuropsychiatric effects (n=4; 0.8%), elevated transaminase levels and hyperlactatemia (n= 3; 0.6%), and peripheral neuropathy (n=2; 0.4%). Complete regimen change due to treatment failure was more common in patients with CD4+ cell count <50cells/mm3 (p<0.001) at ART initiation and body mass index greater than 25 kg/m2 (p=0.01) at entry into the study. Conclusion—Both drug switches and complete regimen change were uncommon in patients cotreated for TB-HIV with the chosen regimen. Patients with severe immunosuppression need to be monitored carefully, as they were most at risk for treatment failure requiring regimen change.
Comparing the outcomes of nurse initiated management of antiretroviral therapy in Tuberculosis - Human immunodeficiency Virus (HIV) co-infected patients Vs HIV mono-infected patients.
(2016) Jithoo, Niraksha.; Knight, Stephen Eric.; Naidoo, Kogieleum.
No abstract available.
Considerations for biomarker-targeted intervention strategies for tuberculosis disease prevention.
(Elsevier., 2018) Fiore-Gartland, Andrew.; Carpp, Lindsay N.; Naidoo, Kogieleum.; Thompson, Ethan.; Zak, Daniel E.; Self, Steven G.; Churchyard, Gavin J.; Walzl, Gerhard.; Penn-Nicholson, Adam.; Scriba, Thomas J.; Hatherill, Mark.
Abstract available in pdf.
Cost-effectiveness of initiating antiretroviral therapy at different points in TB treatment in HIV-TB co-infected ambulatory patients in South Africa.
(Wolters Kluwer., 2015) Naidoo, Kogieleum.; Grobler, Anna Christina.; Deghaye, Nicola.; Reddy, Tarylee.; Gengiah, Santhanalakshmi.; Gray, Andrew Lofts.; Abdool Karim, Salim Safurdeen.
Abstract available in pdf.
Defining the role of high-dose isoniazid in the treatment of multi-drug resistance tuberculosis: isoniazid resistant profiling.
(2021) Ngema, Senamile Lale.; Dookie, Navisha.; Naidoo, Kogieleum.
Background: High-dose isoniazid is recommended in short-course regimens for multidrug-resistant tuberculosis (MDR-TB). However, there is no substantial evidence supporting its use in the presence of INH resistant mutations. Therefore, this study aimed to establish the efficacy of INH in the presence INH resistance associated mutations. Methods: We selected 94 clinical isolates obtained from 65 patients from the IndEX (CAP020) study specimen biorepository. Isolates were selected based on whole genome sequencing results showing evidence of INH resistant conferring mutations. Twenty-one isolates had inhA promoter gene and/ inhA coding region mutations, 35 had katG mutations, and 20 had both inhA promoter and/ inhA coding region plus katG mutations. Additionally, 18 INH susceptible clinical isolates were included in this analysis. Minimum inhibitory concentrations (MICs) were done in different concentration ranges depending on the mutation present. INH susceptible and H37Rv (0.016-0.256) μg/ml, inhA (0.256-4.0) μg/ml, katG (1.0-16.0) μg/ml and inhA plus katG (4.0-16) μg/ml. Results: Among 94 isolates, 36 were excluded: 11 MPT64 antigen negative, 23 non-growers and two were contaminated. Fifty-eight isolates from 55 patients were left for analysis. Eleven isolates had inhA mutations, 23 katG mutations, 12 had double mutations in inhA and katG, and 12 were INH susceptible. MICs obtained varied within isolates ranging from 0.016 to >64.0 μg/ml. InhA, katG, inhA plus katG mutations and INH susceptible isolates had median INH MIC of 8.0 (4.0-64.0), 4.0 (95% CI, 4.0-8.0), 64.0 (95% CI, 64.0-64.0), and 0.48 (95% CI, 0.32-1.0) μg/ml, respectively, confirming the association between INH MICs and genotypic profile. The MDR-TB and pre/XDR-TB had median INH MIC of 8.0 (95% CI, 8.0-32.0) and 48.0 (4.0-64.0) μg/ml, respectively. We found association between cavitary disease and increase in INH MICs for inhA mutants, median of 64.0 (64.0-64.0) μg/ml, and previous TB history and increased INH MICs (8.0[95% CI, 8.0-64]. Conclusion: This study demonstrated highly variable MIC range with significant overlap in MIC range among the mutant groups. Furthermore, inhA mutants demonstrated unexpectedly high MICs raising a concern for the ongoing use of the high-dose INH in our setting. Our findings suggest that the current one-size-fits all approach to MDR-TB short-course regimen requires urgent review.
Detection of drug metabolizing enzyme gene (DMEs) polymorphisms among the Zulu population of South Africa.
(2007) Makume, Mantha Thandiwe.; Naidoo, Richard.; Naidoo, Kogieleum.; Chelule, Paul Kiprono.
The ability to metabolise drugs and achieve positive therapeutic outcomes is dependent on both genetic and environmental factors. The focus of this study was to determine the distribution and frequency of clinically relevant DME alleles and to assess the impact of these DME alleles on therapeutic outcomes in a cohort of 50 HIV-TB co-infected Zulu participants. PCR-RFLP was used to generate a genotypic profile of CYPIA2, 2C9, 2C19, 2E1, 3A4, MDR-1 and NAT-2. The distributions of the allelic frequencies were as follows. The CYPIA2 (A) - 50.7%, CYP2C9*2 — 100% and *3 — 56.2%, CYP2C19*2 — 35.4%, CYP2E1 (C2) — 28.4%, CYP3A4*1B (G) — 58.2%, MDR-1 (C3435T) - 16% and NAT-2 slow acetylators — 6.5%. Seventy-three percent of participants had prolonged TB therapy. Within this group, 82.9% of patient displayed wild type and 17.2% variant allele for CYP2E1 gene (p= 0.04) profile. In addition, all the slow acetylators in this study had prolonged TB therapy. In the MDR-1 gene, 87.5% showed wild type allele and 12.5% displayed the variant allele. Unsuccessful TB outcomes were also noted in 22% of this study population. In this group the variant allele was found to be dominant in CYPIA2, CYP3A4 and NAT-2, the opposite was seen in CYP2E1 and MDR-1. It was also interesting to note a similar genetic profile in the group that showed successful TB therapy outcomes. All participants had positive ARV treatment outcomes despite DME genotypic variations. However, 26% of all study participants experienced liver enzyme abnormalities. These findings concur with other studies regarding the ethnic distribution of DME alleles and evidence of an association between ART and TB therapeutic outcomes and DME genotype variation was inconclusive.
Developing a provincial epidemiologic and demographic information system for health policy and planning in Kwazulu-Natal.
(2000) Buso, D. L.; Jinabhai, Champaklal Chhaganlal.; Naidoo, Kogieleum.
Since 1994, a turning point in the history of South Africa (SA), significant changes were made in the delivery of health services by the public sector, provincially and nationally. The process of change involved making important decisions about health services provision, often based on past experience but ideally requiring detailed information on health status and health services. For an example, Primary Health Care (PHC) was made freely accessible to all citizens of this country. Many studies on the impact of free PHC in the country have shown increased utilization of these services.40 In the context of HIV/AIDS and its complications and other emerging health conditions, reasons for this increased utilization may not be that simple. I17, II8. Parallel with increased utilisatIon has been uncontrollable escalation of costs in the Department of Health (DoH), often resulting in ad-hoc and ineffective measures of cost-containment.40. For these and many other reasons of critical importance to public health services management, the issue of health information generally, and epidemiological inforn1ation in particular, should be brought higher on the agenda of health management. Public health services management is about planning, organization, leading, monitoring and control of the same services.2 Any public health plan must have a scientific basis. In order to achieve rational planning of public health services in the province, adequate, up to date, accurate information must be available, as a planning tool. Health information is one of key resources and an essential element in health services management. It is a powerful tool by which to assess health needs, to measure health status of the population and most importantly, to decide how resources should be deployed.5 Trends in the health status of the population are suggested by the White Paper for transforn1ation of Health Services (White Paper), to be important indicators of the success of the Reconstruction and Development Programme (RDP), the country's programme of transformation. 37,39 It is within that context that the KwaZulu-Natal-Department of Health (KZN-DoH) resolved to establish an Epidemiology/Demographic Unit for the province, to assist management to achieve the department's objectives of providing equitable, effective, efficient and comprehensive health services. 37,89 Purpose: To develop a provincial Epidemiological-Demographic Inforn1ation System (EDIS) that will consistently inforn1 and support rational and realistic management decisions based on accurate, timely, current and comprehensive infom1ation, moving the DoH towards evidence based policy and planning. Objectives: To provide an ED IS framework to : .develop provincial health policy .assist management with health services planning and decision-making .ensure central co-ordination of health information in order to support delivery of services at all levels of the health system . . monitor implementation and evaluation of health programmes . ensure utilization of information at the point of collection, for local planning and interventlon. Methods: A rapid appraisal of the existing Health Information System (HIS) in the province was conducted from the sub-departments of the DoH and randomly selected institutions. A cross-sectional study involving retrospective review of records from selected hospitals, clinics and other sources, was conducted. The study period was the period between January 1998 to December 1998. Capacity at district and regional levels on managing health information and epidemiological information in particular, was reviewed and established through training progranmles. Results: The rapid appraisal of existing HIS in the province revealed a relatively electronically well resourced sub-department of Informatics within the KZN-DoH, with a potential to provide quality and timely data. However, a lot of data was collected from both clinics and hospitals but not analyzed nor utilized. Some critical data was captured and analyzed nationally. There was lack of clarity between the Informatics Department staff responsible for collecting and processing provincial data and top management with regards each other's needs. Demographics: The demographic composition and distribution profile of the KZN population showed features of a third world country for Blacks with the White population displaying contrasting first world characteristics. Socio-Economic Profile: The majority of the population was unemployed, poor, illiterate, economically inactive, and earning very low income. The water supply, housing and toilet facilities seemed adequate, but in the absence of data on urban/rural distinction, this finding needs to be interpreted with caution Epidemiology: All basic indicators of socio-economic status (infant, child, neonatal mortality rates) were high and this province had the second poorest of the same indicators in the country. Adult and child morbidity and mortality profiles of the province, both at clinics and district hospitals were mainly from preventable conditions. Indicators on women and maternal health were consistent with the socio-economic status of this province; and maternal mortality rate was high with causes of mortality that were mainly preventable. The issue of HIV / AIDS complications remains unquantifiable with the limited data available. HIV is a serious epidemic in KZN and this province continues to lead all the provinces in the country, a prevalence of 32 % in 1999.86 Health Services Provision: Inmmnization coverage was almost 50% below the national target and drop out rate was very high. Termlinations of Pregnancies (TOP) occurred mainly among adult, single women, and the procedure done within the first trimester and requested for social and economic reasons. Provincial clinics (mainly fixed) and hospitals provide family planning and Ante Natal Care (ANC) services to the majority of pregnant women in the province. Conclusion : KZN is a poor province with an epidemiological profile of a country in transition but predominantly preventable health conditions. The province has a potential for producing high quality health information required for management, planning and decision making. It is recommended that management redirects resources towards improving PHC services. Establishment of an Epidemiology Unit would facilitate the DoH's health services reforms, through provision of comprehensive, accurate, timely and relevant health information .
Dolutegravir for first-line antiretroviral therapy in low-income and middle-income countries: uncertainties and opportunities for implementation and research.
(Elsevier., 2018) Dorward, Jienchi.; Lessells, Richard John.; Drain, Paul K.; Naidoo, Kogieleum.; De Oliveira, Tulio De Paiva Nazareth Andrade.; Pillay, Yogan.; Abdool Karim, Salim Safurdeen.; Garrett, Nigel Joel.
Abstract available in pdf.
Early experiences with Isoniazid Preventive Therapy roll-out in an ART programme : a pharmacist's perspective.
(2016) Maharaj, Bhavna.; Yende-Zuma, Fortunate Nonhlanhla.; Naidoo, Anushka.; Gengiah, Santhanalakshmi.; Naidoo, Kogieleum.
Tuberculosis (TB) remains the leading cause of mortality amongst people infected with Human Immunodeficiency Virus (HIV). Additionally, TB recurrence after successful treatment completion occurs more frequently amongst HIV positive people. Isoniazid provided as part of isoniazid preventive therapy (IPT) has been the gold standard of TB preventive therapy provision for the last few decades. IPT has been recommended by the World Health Organisation (WHO) and implemented by national health programmes in countries across the world. Despite global efforts and campaigns to promote IPT, uptake still remains a challenge and, progress in the operational scale- up of IPT is slow. Both international and in-country guidelines have advanced to recommending the use of IPT in HIV infected patients who have previously been treated for TB because these patients remain at risk for recurrent TB especially in TB endemic settings. However, there still remains a paucity in data on the successful programmatic use of IPT secondary to previous cured TB among HIV infected patients and is the focus of the current analysis from a pharmacists’ perspective. Methods: A retrospective secondary analysis was conducted from October 2009 to October 2013, amongst HIV infected patients, previously treated for TB, accessing HIV care at the urban CAPRISA clinical research clinic in Durban, South Africa. The aim of the study was to evaluate the implementation of Isoniazid Preventive Therapy (IPT) within the parent study titled “TB recurrence upon treatment with HAART” (TRuTH). Data was collected on IPT uptake, course completion, drug toxicity, treatment interruption, and the occurrence of incident TB either during treatment or post IPT completion. The multidisciplinary team approach in providing IPT to at risk HIV infected patients, including the specific role of the pharmacist, was also assessed. Results: There were 402 patients enrolled in the parent study. Of these 344 (85.6%) were eligible to receive IPT and of whom 212 (61.6%) initiated IPT. Among those that commenced IPT, 184 (86.8%) completed the six-month course, 24 (11.3%) permanently discontinued IPT and of these, 3.8% discontinued due to side effects. More women (n=130; 61.3%) were initiated on IPT (p=0.001) than men. Overall median adherence to IPT was 97.6% (IQR: 94.2 - 99.4). There were 22 cases of incident TB in this cohort: 13 occurred prior to IPT and nine after IPT (incidence rate ratio 0.67; 95% CI 0.29- 1.58; p=0.362). CONCLUSIONS: Overall, we demonstrated a successful IPT roll-out in a high TB endemic setting with good uptake of IPT, minimal course interruptions or side effects reported. IPT is a safe and tolerable TB prevention intervention within ART programmes and importantly amongst patients on ART with previous TB treatment experience. The pharmacist played an important role in continuum of care in IPT provision within an ART programme. This role included ensuring stable supply chain management, supporting clinic staff in monitoring safe IPT use and provided data on IPT course completion rates
Effect of rifampicin and efavirenz on moxifloxacin concentrations when co-administered in patients with drug-susceptible TB.
(Oxford University Press., 2017) Naidoo, Anushka.; Chirehwa, Maxwell.; McIlleron, Helen.; Naidoo, Kogieleum.; Essack, Sabiha Yusuf.; Yende-Zuma, Fortunate Nonhlanhla.; Kimba-Phongi, Eddy.; Adamson, John.; Govender, Katya.; Padayatchi, Nesri.; Denti, Paolo.
Abstract available in pdf.
The effect of timing of initiation of antiretroviral therapy on loss to follow-up in HIV-tuberculosis coinfected patients in South Africa: an open-label, randomized, controlled trial.
(Wolters Kluwer Health., 2016) Yende-Zuma, Fortunate Nonhlanhla.; Naidoo, Kogieleum.
Abstract available in PDF file.
Effects of a reduced dose of Stavudine on the incidence and severity of peripheral neuropathy in HIV-infected adults in South Africa.
(International Medical Press., 2011) Pahuja, Meera.; Grobler, Anna Christina.; Glesby, Marshall J.; Karim, Farina.; Parker, Gary.; Gumede, Sizwe.; Naidoo, Kogieleum.
BACKGROUND—Although recent WHO guidelines recommend withdrawing stavudine (d4T) from first-line ART therapy, it remains commonly used in resource-constrained settings. In 2006, WHO recommended decreasing the dose of d4T from 40mg to 30mg to mitigate toxicities. We compared the incidence and severity of peripheral neuropathy (PN) by d4T dose in a retrospective cohort study. METHODS—Patients’ charts from an ART-naïve population at a rural clinic in KZN, South Africa were retrospectively reviewed for signs and symptoms of incident PN and were graded for severity using the DAIDs scale. Patients enrolled prior to the WHO guideline change were enrolled if they were on d4T 40mg for at least 6 months. After the guideline change all patients were initiated on d4T 30mg. RESULTS—A total of 475 patients were analyzed; 235 in the 40mg cohort (152.7 person-years [py]) and 240 in the 30mg cohort (244.7py). Incidence of peripheral neuropathy was 90.4/100 py (95% CI:75.9–106.8) in the 40mg cohort versus 40.5/100py (95% CI:32.9–49.3) in the 30mg group (incidence rate ratio [IRR]=0.45, p<0.0001). There was no difference in proportion of severe peripheral neuropathy cases (grade 3/4) between the cohorts; 8.3% in the 40mg group and 8.9% in the 30mg group (p=1.0). In a multivariate analysis risk of peripheral neuropathy was associated with increasing age (HR=1.65 95% CI:1.24–2.19), 40 mg dose (HR=2.1, 95% CI:1.61–2.74) and concurrent tuberculosis therapy (HR= 1.41 95% CI:1.06–1.87). CONCLUSION—Incidence of peripheral neuropathy in the 40mg cohort was extremely high and though lower in the 30mg cohort, the rate was nonetheless unacceptably high.
Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy : a multicountry open-label randomised controlled trial.
(Elsevier., 2016) Hosseinipour, Mina C.; Bisson, Gregory P.; Miyahara, Sachiko.; Sun, Xin.; Moses, Agnes.; Riviere, Cynthia.; Kirui, Fredrick Kipkorir.; Badal-Faesen, Sharla.; Lagat, David.; Nyirenda, Mulinda.; Naidoo, Kogieleum.; Hakim, James.; Mugyenyi, Peter.; Henostroza, German.; Leger, Paul D.; Lama, Javier R.; Mohapi, Lerato.; Alave, Jorge.; Mave, Vidya.; Veloso, Valdilea G.; Pillay, Sandy.; Kumarasamy, Nagalingeswaran.; Bao, Jing.; Hogg, Evelyn.; Jones, Lynne.; Zolopa, Andrew.; Kumwenda, Johnstone.; Gupta, Amita.
Abstract available in PDF file.
The epidemiology and impact of pretreatment HIV drug resistance in adults in South Africa.
(2018) Chimukangara, Benjamin.; De Oliveira, Tulio De Paiva Nazareth Andrade.; Naidoo, Kogieleum.; Samuel, Reshmi.
HIV drug resistance (HIVDR) present prior to initiating or re-initiating antiretroviral therapy (ART), is known as pretreatment drug resistance (PDR). Conventionally, PDR is detected by Sanger sequencing. Drug resistant minority variants (DRMVs) that are not reliably detected by Sanger sequencing can be detected by next generation sequencing. The aims of this research were to assess levels of PDR in HIV hyper-endemic areas (with high HIV incidence and prevalence) in KwaZulu-Natal (KZN) province, trends of PDR in South Africa, and the impact of DRMVs on ART. To assess PDR in adults from KZN hyper-endemic areas, 1845 sequences were analyzed from two population-based HIV surveillance studies; a longitudinal HIV surveillance programme in northern KZN (2013-2014), and the HIV Incidence Provincial Surveillance System (HIPSS) in central KZN (2014-2015). Overall, 182/1845 (10.0%) had NNRTI-PDR mutations, and when analyzed by study year, NNRTI-PDR was 10.2% (CI:7.5-12.9) for the HIPSS study in 2014. To assess PDR trends in South Africa, 6880 HIV-1 sequences were collated from 38 datasets of ART-naïve adults (2000-2016). Increasing levels of PDR were observed, most marked from 2010. Crude pooled prevalence of NNRTI-PDR reached 10% in 2014, with a 1.18-fold (CI:1.13- 1.23) annual increase (p<0.001), consistent with findings from the HIPSS data. This provided the first evidence of high-level NNRTI-PDR in KZN and South Africa, supporting the transition to dolutegravir in standard first-line ART, as recommended by the World Health Organization when NNRTI-PDR reaches ≥10%. A case-control (2:1) study in HIV/TB co-infected adult patients was done to assess the impact of DRMVs at different thresholds. Cases were patients that initiated ART and had viral loads ≥1000 copies/mL after ≥6 months on ART, and controls were those that initiated ART and achieved virologic suppression through 24 months. Pre-ART NNRTI-resistance was associated with ART failure. NGS improved detection of HIVDR at lower thresholds, but reduced the specificity of identifying patients at risk of virologic failure, with the specificity reducing from 97% (CI:92-99) at 20% threshold, to 79% (CI:71-86) at 2% threshold. In all, the findings presented in this thesis provide a broad message about the need to improve quality in HIV prevention and treatment services.
Evaluation of a synthetic peptide for the detection of anti-Mycobacterium tuberculosis curli pili IgG antibodies in patients with pulmonary tuberculosis.
(Elsevier., 2018) Naidoo, Natasha.; Pillay, Balakrishna.; Bubb, Martin Owen.; Pym, Alexander S.; Chiliza, Thamsanqa Emmanuel.; Naidoo, Kogieleum.; Ndung'u, Peter Thumbi.; Kasprowicz, Victoria.; Pillay, Manormoney.
Abstract available in pdf.