Browsing by Author "Sunpath, Henry."

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The association of early neonatal feeding on clinical outcomes and cytotoxic T lymphocyte (CTL) responses in HIV exposed low birth weight infants.
(2011) Dassaye, Reshmi.; Coutsoudis, Anna.; Sunpath, Henry.
BACKGROUND Sub-saharan Africa remains to date at the forefront of the HIV/AIDS epidemic. Despite breastfeeding being a significant mode of postnatal HIV transmission it remains the main nutritional source and pillar of child survival for the majority of infants born in Africa. It is therefore, not surprising that considerable research has centred on making breastfeeding safer in terms of HIV transmission. The flash heat treatment method (HTEBM) provides a unique opportunity to safely breastfeed infants but prevent mother-to-child transmission of HIV. Cytotoxic T lymphocyte (CTL) responses have been well documented in HIVinfected adults and children. However, there is a lack of literature on CTL responses in HIV exposed low birth weight infants. This pilot study attempted to examine the association of early neonatal feeding on the clinical outcomes and CTL responses in HIV exposed low birth weight infants. METHODS Seventy-seven patients that fulfilled inclusion and exclusion criteria were enrolled. The clinical outcomes of these patients were evaluated over a 9 month period. Fifty-five of these patients were also investigated for cytotoxic T lymphocyte (CTL) responses by means of the IFNγ ELISpot (megamatrix and confirmation) assays at the 6 weeks, 3, 6,and 9 months follow-up. RESULTS Two HIV-1 infected infants generated a CTL response at a single time point using the ELISPOT matrix screening assay. These responses could not be confirmed and were undetectable at any of the consecutive visits. At the time of detection of responses the infants were fed unheated breastmilk. HIV-1 exposed uninfected infants were unable to elicit a HIV-1-specific CTL response irrespective of feed. With regards to clinical outcomes, infants born o HIV infected mothers with a CD4 count < 500cells/μl were 2x more likely to acquire other infections at birth compared to those infants born to HIV infected mothers with a CD4 count >500cells/μl. Also, infants born to HIV infected mothers with advanced disease (CD4 count 0-200 cells/μl) had a lower birth weight compared to infants born to HIV-1 infected mothers with a CD4 count > 350 cells/μl. We also investigated the feasibility of the flash heat treatment method at birth. While inhospital, 38 HIV-1 infected women fed their infants HTEBM after receiving counseling and support from the nursing staff at the King Edward VIII hospital. The numbers decreased rapidly post hospital discharge, mainly due to mixed feeding. DISCUSSION In conclusion we have shown that it is feasible for HIV infected mothers to heat treat their expressed breastmilk during hospital admission. Furthermore, we were able to demonstrate in this small cohort of patients that the clinical outcomes and growth parameters of infants fed HTEBM were similar to that of infants fed either formula or unheated breastmilk. We were unable to demonstrate HIV-specific responses in the infected infants or the uninfected infants who had been exposed to heat inactivated virus in HTEBM. Our findings indicate that this pilot study was limited in its ability to detect CTL responses in HIV exposed low birth weight infants and further studies are warranted.
Case management and clinical outcomes of people living with HIV and admitted to a state-aided district hospital in Durban, South Africa in 2007.
(2011) Sunpath, Henry.; Knight, Stephen Eric.
Title: Case Management and Clinical Outcomes of People Living with HIV and Admitted to a State-aided District Hospital in Durban, South Africa in 2007. Introduction: A proportion of the many patients who have advanced AIDS in South Africa present for the first time requiring admission to hospital, the number of which are limited by the availability of beds. Novel ways were developed to offer subacute inpatient care at Siyaphila, a facility linked to McCord Hospital in Durban to provide expedited or immediate antiretroviral therapy (ART) (exposed) for patients with advanced disease before their discharge (ART group) . Different components of palliative care were offered for those who did not enter the inpatient ART programme or who were terminally ill (non-ART group) (non-exposed) . Aim: The aim of the study is to describe the clinical condition, inpatient case management and outcomes before discharge of people living with HIV admitted to Siyaphila in order to assist in developing appropriate protocols for inpatient care. Methods: This was an observational, analytic, cohort study using a convenience sample of all patients consecutively admitted to Siyaphila during nine months in 2006/2007. Prevalence of AIDS defining conditions at Siyaphila, time taken to progress from one stage of care to another and outcomes for the two groups before discharge were determined. Univariate and multivariate logistic regression analysis was performed on the ART group to identify risk factors for mortality before discharge. A comparison between the ART and non-ART group was also undertaken. Results: Among the cohort of 405 PLHIV enrolled at Siyaphila during the study period only 171 (42%) were initiated on ART immediately. In all patients, tuberculosis (251; 62%) was the most common opportunistic infection followed by cryptococcal meningitis (68; 17%) and Pneumocystis pneumonia (28; 7%). The mean baseline CD4 cell count was 84 celis/uL for the non-ART group and 55 celis/uL for the ART group. (p <0.01) The median time from initial admission until discharge was 13 days in the non-ART group and 18 days in the ART group. The mortality before discharge among the non-ART group was 24% compared to 6% among the ART group. (p =0.001). The median number of days before ART was initiated was 14 days. Immune reconstitution inflammatory syndrome was diagnosed in seven patients (4%) among the admissions but caused no deaths. In the multivariate analysis, the odds ratio for mortality for patients under 40 years was 0.1 (95% Confidence Interval: 0.01 - 0.9). Conclusions: Subacute care offered at Siyaphila provides an entry point into the ART programme for non-ambulatory patients who in the KwaZulu-Natal context have low ART uptake after discharge. The findings of this study should be adopted as the best clinical practice for PLHIV and AIDS admitted in the late stages of the disease. 0Nords 423) Title: Case Management and Clinical Outcomes of People Living with HIV and Admitted to a State-aided District Hospital in Durban, South Africa in 2007. Introduction: A proportion of the many patients who have advanced AIDS in South Africa present for the first time requiring admission to hospital, the number of which are limited by the availability of beds. Novel ways were developed to offer subacute inpatient care at Siyaphila, a facility linked to McCord Hospital in Durban to provide expedited or immediate antiretroviral therapy (ART) (exposed) for patients with advanced disease before their discharge (ART group) . Different components of palliative care were offered for those who did not enter the inpatient ART programme or who were terminally ill (non-ART group) (non-exposed). Aim: The aim of the study is to describe the clinical condition, inpatient case management and outcomes before discharge of people living with HIV admitted to Siyaphila in order to assist in developing appropriate protocols for inpatient care. Methods: This was an observational, analytic, cohort study using a convenience sample of all patients consecutively admitted to Siyaphila during nine months in 2006/2007. Prevalence of AIDS defining conditions at Siyaphila, time taken to progress from one stage of care to another and outcomes for the two groups before discharge were determined. Univariate and mUltivariate logistic regression analysis was performed on the ART group to identify risk factors for mortality before discharge. A comparison between the ART and non-ART group was also undertaken. Results: Among the cohort of 405 PLHIV enrolled at Siyaphila during the study period only 171 (42%) were initiated on ART immediately. In all patients, tuberculosis (251; 62%) was the most common opportunistic infection followed by cryptococcal meningitis (68; 17%) and Pneumocystis pneumonia (28; 7%). The mean baseline CD4 cell count was 84 celis/uL for the non-ART group and 55 celis/uL for the ART group. (p <0.01) The median time from initial admission until discharge was 13 days in the non-ART group and 18 days in the ART group. The mortality before discharge among the non-ART group was 24% compared to 6% among the ART group. (p =0.001). The median number of days before ART was initiated was 14 days. Immune reconstitution inflammatory syndrome was diagnosed in seven patients (4%) among the admissions but caused no deaths. In the mUltivariate analysis, the odds ratio for mortality for patients under 40 years was 0.1 (95% Confidence Interval: 0.01 - 0.9). Conclusions: Subacute care offered at Siyaphila provides an entry point into the ART programme for non-ambulatory patients who in the KwaZulu-Natal context have low ART uptake after discharge. The findings of this study should be adopted as the best clinical practice for PLHIV and AIDS admitted in the late stages of the disease. (Words 423)
Characterization of nucleoside reverse transcriptase inhibitor-associated mutations in the RNAse H region of HIV-1 subtype c infected individuals.
(Viruses., 2017) Ngcapu, Sinaye.; Theys, Kristof.; Libin, Pieter.; Marconi, Vincent C.; Sunpath, Henry.; Ndung'u, Peter Thumbi.; Gordon, Michelle Lucille.
Abstract available in pdf.
Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa : implications for future treatment options.
(Lippincott Williams & Wilkins., 2011) Singh, Ashika.; Sunpath, Henry.; Green, Taryn N.; Padayachi, Nagavelli.; Hiramen, Keshni.; Lie, Yolanda.; Anton, Elizabeth D.; Murphy, Richard.; Reeves, Jacqueline D.; Kuritzkes, Daniel R.; Ndung'u, Peter Thumbi.
Background: Drug resistance poses a significant challenge for the successful application of highly active antiretroviral therapy (HAART) globally. Furthermore, emergence of HIV-1 isolates that preferentially use CXCR4 as a coreceptor for cell entry, either as a consequence of natural viral evolution or HAART use, may compromise the efficacy of CCR5 antagonists as alternative antiviral therapy. Methods: We sequenced the pol gene of viruses from 45 individuals failing at least 6 months of HAART in Durban, South Africa, to determine the prevalence and patterns of drug-resistance mutations. Coreceptor use profiles of these viruses and those from 45 HAART-naive individuals were analyzed using phenotypic and genotypic approaches. Results: Ninety-five percent of HAART-failing patients had at least one drug-resistant mutation. Thymidine analog mutations (TAMs) were present in 55% of patients with 9% of individuals possessing mutations indicative of the TAM1 pathway, 44% had TAM2, whereas 7% had mutations common to both pathways. Sixty percent of HAART-failing subjects had X4/dual//mixed-tropic viruses compared with 30% of HAART-naïve subjects (P < 0.02). Genetic coreceptor use prediction algorithms correlated with phenotypic results with 60% of samples from HAART-failing subjects predicted to possess CXCR4-using (X4/dual/mixed viruses) versus 15% of HAART-naïve patients. Conclusions: The high proportion of TAMs and X4/dual/mixed HIV-1 viruses among patients failing therapy highlight the need for intensified monitoring of patients taking HAART and the problem of diminished drug options (including CCR5 antagonists) for patients failing therapy in resource-poor settings.