Low uptake of antiretroviral therapy after admission with human immunodeficiency virus and tuberculosis in KwaZulu-Natal, South Africa.

A prospective cohort study was conducted among human immunodeficiency virus (HIV) infected in-patients with tuberculosis (TB) or other opportunistic infections (OIs) in South Africa to estimate subsequent antiretroviral therapy (ART) uptake and survival

Pediatric Response to Second-Line Antiretroviral Therapy in South Africa

Background: With improved access to pediatric antiretroviral therapy (ART) in resource-limited settings, more children could experience first-line ART treatment failure. Methods: We performed a retrospective cohort analysis using electronic medical records from HIV-infected children who initiated ART at McCord Hospital's Sinikithemba Clinic in KwaZulu-Natal, South Africa, from August 2003 to December 2010. We analyzed all records from children who began second-line ART due to first-line treatment failure. We used logistic regression to compare viral outcomes in Protease Inhibitor (PI)-based versus Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-based second-line ART, controlling for time on first-line ART, sex, and whether HIV genotyping guided the regimen change. Results: Of the 880 children who initiated ART during this time period, 80 (9.1%) switched to second-line ART due to therapeutic failure of first-line ART after a median of 95 weeks (IQR 65–147 weeks). Eight (10%) of the failures received NNRTI-based second-line ART, all of whom failed a PI-based first-line regimen. Seventy (87.5%) received PI-based second-line ART, all of whom failed a NNRTI-based first-line regimen. Two children (2.5%) received non-standard dual therapy as second-line ART. Six months after switching ART regimens, the viral suppression rate was significantly higher in the PI group (82%) than in the NNRTI group (29%; p = 0.003). Forty-one children (51%) were tested for genotypic resistance prior to switching to second-line ART. There was no significant difference in six month viral suppression (p = 0.38) between children with and without genotype testing. Conclusion: NNRTI-based second-line ART carries a high risk of virologic failure compared to PI-based second-line ART

Coadministration of lopinavir/ritonavir and rifampicin in HIV and tuberculosis co-infected adults in South Africa

In HIV-infected patients receiving rifampicin-based treatment for tuberculosis (TB), the dosage of lopinavir/ritonavir (LPV/r) is adjusted to prevent sub-therapeutic lopinavir concentrations. In this setting, South African clinicians were advised to administer super-boosted LPV/r (400 mg/400 mg) twice daily, instead of standard dosed LPV/r (400 mg/100 mg) twice daily. We sought to determine--in routine practice--the tolerability and HIV treatment outcomes associated with super-boosted LPV/r compared to unadjusted LPV/r in combination with rifampicin-based TB treatment

Outcomes After Virologic Failure of First-Line ART in South Africa

Article approval pendingTo determine initial 24-week outcomes among prospectively enrolled patients with failure of initial antiretroviral therapy (ART)

Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa: implications for future treatment options

Article approval pendingDrug 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

Case management and clinical outcomes of people living with HIV and admitted to a state-aided district hospital in Durban, South Africa in 2007.

Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2011.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

Early warning indicators for first-line virologic failure independent of adherence measures in a South African urban clinic.

Abstract We sought to develop individual-level Early Warning Indicators (EWI) of virologic failure (VF) for clinicians to use during routine care complementing WHO population-level EWI. A case-control study was conducted at a Durban clinic. Patients after≥5 months of first-line antiretroviral therapy (ART) were defined as cases if they had VF [HIV-1 viral load (VL)>1000 copies/mL] and controls (2:1) if they had VL≤1000 copies/mL. Pharmacy refills and pill counts were used as adherence measures. Participants responded to a questionnaire including validated psychosocial and symptom scales. Data were also collected from the medical record. Multivariable logistic regression models of VF included factors associated with VF (p<0.05) in univariable analyses. We enrolled 158 cases and 300 controls. In the final multivariable model, male gender, not having an active religious faith, practicing unsafe sex, having a family member with HIV, not being pleased with the clinic experience, symptoms of depression, fatigue, or rash, low CD4 counts, family recommending HIV care, and using a TV/radio as ART reminders (compared to mobile phones) were associated with VF independent of adherence measures. In this setting, we identified several key individual-level EWI associated with VF including novel psychosocial factors independent of adherence measures

A high incidence of nucleoside reverse transcriptase inhibitor (NRTI)-induced lactic acidosis in HIV-infected patients in a South African context

Objective. To determine the incidence of and predisposing risk factors for lactic acidosis in HIV-infected patients on antiretroviral drugs in South Africa. Design. Observational case series. Setting. Sinikithemba HIV Clinic, McCord Hospital, Durban. Subjects. Eight hundred and ninety-one HIV-positive patients on highly active antiretroviral therapy (HAART) during an 18-month period commencing in January 2004. Measurements and results. Fourteen cases of lactic acidosis (incidence rate of 19 (95% confidence interval (CI): 9 - 29) cases per 1 000 person-years of treatment) were reported. All cases were female, with a median age of 36 years and a median weight of 81 kg. The median time on HAART before developing lactic acidosis was 7.5 months and the median peak lactate level was 9.3 mmol/l. All cases were on stavudine (d4T), lamivudine (3TC) and 1 non-NRTI. The case mortality rate was 29% (4 patients). Conclusions. The incidence rate is higher than reported in studies in developed countries. This may be due to d4T, which is recommended as a first-line antiretroviral drug in South Africa. This implication raises the question whether it is an appropriate drug in first-line treatment of patients with predisposing risk factors such as female gender and being overweight. South African Medical Journal Vol. 96(8) 2006: 722-72

A nurse-led intervention to improve management of virological failure in public sector HIV clinics in Durban, South Africa: A pre- and post-implementation evaluation.

BACKGROUND: Identification of patients on antiretroviral therapy (ART) with virological failure (VF) and the response in the public health sector remain significant challenges. We previously reported improvement in routine viral load (VL) monitoring after ART commencement through a health system-strengthening, nurse-led VL champion programme as part of a multidisciplinary team in three public sector clinics in Durban, South Africa. OBJECTIVES: To report on the impact of the VL champion model adapted to identify, support and co-ordinate the management of individuals with VF on first-line ART in a setting with limited electronic-based record capacity. METHODS: We evaluated the VL champion model using a controlled before-after study design. A paper-based tool, the high VL register, was piloted under the supervision of the VL champion to improve data management, monitoring of counselling support, and enacting of clinical decisions. We abstracted chart and electronic data (TIER.net) for eligible individuals with VF in the year before and after implementation of the programme, and compared outcomes for individuals during these periods. Our primary outcome was successful completion of the VF pathway, defined as a repeat VL &lt;1 000 copies/mL or a change to second-line ART within 6 months of VF. In a secondary analysis, we assessed the completion of each step in the pathway. RESULTS: We identified 60 and 56 individuals in the pre-intervention and post-intervention periods, respectively, with VF who met the inclusion criteria. Sociodemographic and clinical characteristics were similar between the periods. Repeat VL testing was completed in 61.7% and 57.8% of individuals in these two groups, respectively. We found no difference in the proportion achieving our primary outcome in the pre- and post-intervention periods: 11/60 (18.3%; 95% confidence interval (CI) 9 - 28) and 15/56 (22.8%; 95% CI 15 - 38), respectively (p=0.28). In multivariable logistic regression models adjusted for potential confounding factors, individuals in the post-intervention period had a non-significant doubling of the odds of achieving the primary outcome (adjusted odds ratio 2.07; 95% CI 0.75 - 5.72). However, there was no difference in the rates of completion of each step along the first-line VF cascade of care. CONCLUSIONS: This enhanced intervention to improve VF in the public sector using a paper-based data management system failed to achieve significant improvements in first-line VF management over the standard of care. In addition to interventions that better address patient-centred factors that contribute to VF, we believe that there are substantial limitations to and staffing requirements involved in the ongoing utilisation of a paper-based tool. A prioritisation is needed to further expand and upgrade the electronic medical record system with capabilities for prompting staff regarding patients with missed visits and critical laboratory results demonstrating VF

Normative scores for a brief neuropsychological battery for the detection of HIV-associated neurocognitive disorder (HAND) among South Africans

<p>Abstract</p> <p>Background</p> <p>There is an urgent need to more accurately diagnose HIV-associated neurocognitive disorder (HAND) in Africa. Rapid screening tests for HIV-associated dementia are of limited utility due to variable sensitivity and specificity. The use of selected neuropsychological tests is more appropriate, but norms for HIV seronegative people are not readily available for sub-Saharan African populations. We sought to derive normative scores for two commonly used neuropsychological tests that generate four test scores -- namely the Trail-Making Test (Parts A and B) and the Digit Span Test [Forward (DSF) and Backward (DSB)]. To assess memory and recall, we used the memory item of the International HIV Dementia Scale (IHDS).</p> <p>Findings</p> <p>One hundred and ten HIV seronegative participants were assessed at McCord Hospital, Durban, South Africa between March 3^rdand October 31^st, 2008. We excluded people with major depressive disorder, substance use abuse and dependence and head injuries (with or without loss of consciousness). All the participants in this study were African and predominantly female with an average age of 28.5 years and 10 years of education. Age and gender influenced neuropsychological functioning, with older people performing worse. The effect of gender was not uniform across all the tests.</p> <p>Conclusion</p> <p>These two neuropsychological tests can be administered with the IHDS in busy antiretroviral clinics. Their performance can be measured against these norms to more accurately diagnose the spectrum and progression of HAND.</p