2023 Southern African HIV Clinicians Society Adult Antiretroviral Therapy Guidelines: What’s new?

No abstract available

Causes of Death on Antiretroviral Therapy: A Post-Mortem Study from South Africa

Background: Mortality in the first months of antiretroviral therapy (ART) is a significant clinical problem in sub-Saharan Africa. To date, no post-mortem study has investigated the causes of mortality in these patients. Methods: HIV-positive adults who died as in-patients at a Johannesburg academic hospital underwent chart-review and ultrasound-guided needle autopsy for histological and microbiological examination of lung, liver, spleen, kidney, bone marrow, lymph node, skin and cerebrospinal fluid. A clinico-pathologic committee considered all available data and adjudicated immediate and contributing causes of death. Results: Thirty-nine adults were enrolled: 14 pre-ART, 15 early-ART (7–90 days), and 10 late-ART (>90 days). Needle sampling yielded adequate specimen in 100% of kidney, skin, heart and cerebrospinal fluid samples, 97% of livers and lungs, 92% of bone marrows, 87% of spleens and 68% of lymph nodes. Mycobacterial infections were implicated in 69% of deaths (26 of 27 of these due to M. tuberculosis), bacterial infections in 33%, fungal infections in 21%, neoplasm in 26%, and non-infectious organ failure in 26%. Immune reconstitution inflammatory syndrome (IRIS) was implicated in 73% of early-ART deaths. Post-mortem investigations revealed previously undiagnosed causes of death in 49% of cases. Multiple pathologies were common with 62% of subjects with mycobacterial infection also having at least one other infectious or neoplastic cause of death. Conclusions: Needle biopsy was efficient and yielded excellent pathology. The large majority of deaths in all three groups were caused by M. tuberculosis suggesting an urgent need for improved diagnosis and expedited treatment prior to and throughout the course of antiretroviral therapy. Complex, unrecognized co-morbidities pose an additional challenge

Impact of Empiric Antimicrobial Therapy on Outcomes in Patients with Escherichia coli and Klebsiella pneumoniae Bacteremia: A Cohort Study

<p>Abstract</p> <p>Background</p> <p>It is unclear whether appropriate empiric antimicrobial therapy improves outcomes in patients with bacteremia due to <it>Escherichia coli </it>or <it>Klebsiella</it>. The objective of this study is to assess the impact of appropriate empiric antimicrobial therapy on in-hospital mortality and post-infection length of stay in patients with <it>Escherichia coli </it>or <it>Klebsiella </it>bacteremia while adjusting for important confounding variables.</p> <p>Methods</p> <p>We performed a retrospective cohort study of adult patients with a positive blood culture for <it>E. coli </it>or <it>Klebsiella </it>between January 1, 2001 and June 8, 2005 and compared in-hospital mortality and post-infection length of stay between subjects who received appropriate and inappropriate empiric antimicrobial therapy. Empiric therapy was defined as the receipt of an antimicrobial agent between 8 hours before and 24 hours after the index blood culture was drawn and was considered appropriate if it included antimicrobials to which the specific isolate displayed <it>in vitro </it>susceptibility. Data were collected electronically and through chart review. Survival analysis was used to statistically assess the association between empiric antimicrobial therapy and outcome (mortality or length of stay). Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).</p> <p>Results</p> <p>Among 416 episodes of bacteremia, 305 (73.3%) patients received appropriate empiric antimicrobial therapy. Seventy-one (17%) patients died before discharge from the hospital. The receipt of appropriate antimicrobial agents was more common in hospital survivors than in those who died (p = 0.04). After controlling for confounding variables, there was no association between the receipt of appropriate empiric antimicrobial therapy and in-hospital mortality (HR, 1.03; 95% CI, 0.60 to 1.78). The median post-infection length of stay was 7 days. The receipt of appropriate antimicrobial agents was not associated with shortened post-infection length of stay, even after controlling for confounding (HR, 1.11; 95% CI 0.86 to 1.44).</p> <p>Conclusion</p> <p>Appropriate empiric antimicrobial therapy for <it>E. coli </it>and <it>Klebsiella </it>bacteremia is not associated with lower in-hospital mortality or shortened post-infection length of stay. This suggests that the choice of empiric antimicrobial agents may not improve outcomes and also provides data to support a randomized trial to test the hypothesis that use (and overuse) of broad-spectrum antibiotics prior to the availability of culture results is not warranted.</p

Performance evaluation of the Pima™ point-of-care CD4 analyser using capillary blood sampling in field tests in South Africa

<p>Abstract</p> <p>Background</p> <p>Point-of-care CD4 testing can provide immediate CD4 reporting at HIV-testing sites. This study evaluated performance of capillary blood sampling using the point-of-care Pima™ CD4 device in representative primary health care clinics doing HIV testing.</p> <p>Methods</p> <p>Prior to testing, prescribed capillary-sampling and instrument training was undertaken by suppliers across all sites. Matching venous EDTA samples were drawn throughout for comparison to laboratory predicate methodology (PLG/CD4). In Phase I, Pima™ cartridges were pipette-filled with EDTA venous blood in the laboratory (N = 100). In Phase II (N = 77), Pima™ CD4 with capillary sampling was performed by a single operator in a hospital-based antenatal clinic. During subsequent field testing, Pima™ CD4 with capillary sampling was performed in primary health care clinics on HIV-positive patients by multiple attending nursing personnel in a rural clinic (Phase-IIIA, N = 96) and an inner-city clinic (Phase-IIIB, N = 139).</p> <p>Results</p> <p>Pima™ CD4 compared favourably to predicate/CD4 when cartridges were pipette-filled with venous blood (bias -17.3 ± STDev = 36.7 cells/mm³; precision-to-predicate %CV < 6%). Decreased precision of Pima™ CD4 to predicate/CD4 (varying from 17.6 to 28.8%SIM CV; mean bias = 37.9 ± STDev = 179.5 cells/mm³) was noted during field testing in the hospital antenatal clinic. In the rural clinic field-studies, unacceptable precision-to-predicate and positive bias was noted (mean 28.4%SIM CV; mean bias = +105.7 ± STDev = 225.4 cells/mm³). With additional proactive manufacturer support, reliable performance was noted in the subsequent inner-city clinic field study where acceptable precision-to-predicate (11%SIM CV) and less bias of Pima™ to predicate was shown (BA bias ~11 ± STDev = 69 cells/mm³).</p> <p>Conclusions</p> <p>Variable precision of Pima™ to predicate CD4 across study sites was attributable to variable capillary sampling. Poor precision was noted in the outlying primary health care clinic where the system is most likely to be used. Stringent attention to capillary blood collection technique is therefore imperative if technologies like Pima™ are used with capillary sampling at the POC. Pima™ CD4 analysis with venous blood was shown to be reproducible, but testing at the point of care exposes operators to biohazard risk related to uncapping vacutainer samples and pipetting of blood, and is best placed in smaller laboratories using established principles of Good Clinical Laboratory Practice. The development of capillary sampling quality control methods that assure reliable CD4 counts at the point of care are awaited.</p

Guidelines for antiretroviral therapy in adults by the Southern African HIV clinicians society

These guidelines are intended as an update to those published in the Southern African Journal of HIV Medicine in January 2008. Since the release of the previous guidelines, the scaleup of antiretroviral therapy (ART) in Southern Africa has continued to grow. Cohort studies from the region show excellent clinical outcomes; however, ART is still being started late (in advanced disease), resulting in relatively high early mortality rates. New data on antiretroviral (ARV) tolerability in the region and several new ARV drugs have become available. Although currently few in number, some patients in the region are failing protease inhibitor (PI)- based second-line regimens. To address this, guidelines on third-line (or ‘salvage’) therapy have been expanded.Specific recommendations provided here are intended only as a guide to clinical therapy, based on expert consensus and best current evidence. Treatment decisions for patients should be made by their responsible clinicians, with due consideration for individual circumstances. The most current version of this document should always be consulted.All expert panel members have completed and submitted conflict of interest disclosure forms. Disclosure information represents the previous 3 years (updated 17 August 2012) and includes relationships with pharmaceutical companies and medical aids: Dr Francesca Conradie has received support from Abbott to attend conferences, and research support from Tibotec. She has also received honoraria for speaking engagements from Abbott and MSD. Dr Hefer has received support to attend conferences from Abbott, Adcock Ingram, Aspen and MSD. He owns shares in Lifecell and has received honoraria for speaking engagements from Abbott, Aspen and MSD. Dr Johnson has received research support from Bristol Myers Squibb (BMS), MSD, Tibotec and Schering-Plough. He has also received honoraria for speaking engagements from Abbott. Professor Graeme Meintjes has received honoraria for speaking engagements from Sanofi Aventis and serves as a consultant for Aid for AIDS. Professor Yunus Moosa has received support to attend conferences from Abbott and honoraria for speaking at conferences/seminars from Abbott, Aspen, MSD and Pfizer. Dr Theresa Rossouw serves as a consultant for Discovery Health. Dr Ebrahim Variava receives support for clinical trials from Outsuka. Professor Francois Venter has received support to attend conferences from Adcock Ingram and MSD; honoraria for speaking engagements from MSD; and has served as a consultant for Abbott, Johnson and Johnson and Tibotec. Dr Eric Goemaere, Professor Gary Maartens, Dr Moeketsi Mathe, Dr Regina Osih and Dr Gilles Van Custem report no conflicts of interest.This work is supported and funded by the Southern African HIV Clinicians Society through an educational grant from Atlantic Philanthropies.www.sajhivmed.org.zaam201

Clinical case study programme

The Southern African HIV Clinicians Society’s online clinical cases are geared at providing excellent continuing medical education for members of the Society. This activity has been created to offer clinicians working in the HIV area access to online education. Cases are written by experienced HIV specialists and can range from general adult HIV/TB through specialist paediatric cases to other related infectious diseases encountered when managing patients with HIV. S Afr J HIV Med 2012;13(2):58

Achieving the National Strategic Plan: A practical calculator for local target setting in district health facilities

The South African HIV National Strategic Plan (NSP) aims to provide access to appropriate treatment, care and support to 80% of the HIV-infected population by 2011. By mid-2008, highly active antiretroviral treatment (HAART) was being dispensed to about half the HIV-infected population in need. Reaching the NSP targets will require full mobilisation of all of South Africa’s health facilities. While the NSP has broad political and programmatic support from the Department of Health and civil society, and managers are able to recite the national targets, it has been difficult for these managers to relate the targets to their own geographical areas of responsibility. National, regional and district targets for HIV care have been set from South Africa’s relatively good census, modelling and epidemiological data. However, few practical tools are available to help clinicians and managers understand their facility's actual contribution to the district regional and national NSP targets for each step of the HIV care pathway (HIV testing, CD4 testing, HAART referral and initiation). The calculation of HAART initiation targets is complicated by the anticipated additional demand for treatment that will be generated by a change in the recommended CD4-count threshold for initiation of treatment.4 Accordingly, we provide a data-based tool that is readily available, and that district and facility managers can use to calculate their annual steady-state HIV testing, CD4 testing and HAART initiation requirements. These calculated values can be used for local and regional planning and to assess and improve current performance at facility level

Impact of recommendation updates in well-controlled patients on non-recommended antiretroviral therapies: the Swiss HIV Cohort Study

INTRODUCTION: HIV treatment recommendations are updated as clinical trials are published. Whether recommendations drive clinicians to change antiretroviral therapy in well-controlled patients is unexplored. METHODS: We selected patients with undetectable viral loads (VL) on non-recommended regimens containing double-boosted protease inhibitors (DBPIs), triple-nucleoside reverse transcriptase inhibitors (NRTIs) or didanosine (ddI) plus stavudine (d4T) at publication of the 2006 International AIDS Society recommendations. We compared demographic and clinical characteristics to those of control patients with undetectable VL not on these regimens, and examined clinical outcome and reasons for treatment modification. RESULTS: At inclusion, 104 patients were in the DBPI group, 436 in the triple-NRTI group, and 19 in the ddI/d4T group. By 2010, 28 (29%), 204 (52%) and 1 (5%) patients were still on DBPIs, triple-NRTIs and ddI plus d4T, respectively. 'Physician decision', excluding toxicity/virological failure, drove 30% of treatment changes. Predictors of recommendation non-observance included female sex (adjusted odds ratio aOR 2.69, 95%CI 1-7.26; P=0.01) for DPBIs, and undetectable VL (aOR 3.53, 95%CI 1.6-7.8; P=0.002) and lack of cardiovascular (CV) events (aOR 2.93, 95%CI 1.23-6.97; P=0.02) for triple-NRTIs. All patient on DBPIs with documented diabetes or a CV event changed treatment. Recommendation observance resulted in lower cholesterol values in the DBPI group (P=0.06), and more patients having undetectable VL (P=0.02) in the triple-NRTI group. DISCUSSION: 'Physician decision' is the main factor driving change from non-recommended to recommended regimens, whilst virological suppression is associated with not switching. Positive clinical outcomes observed post-switch underline the importance of observing recommendations. even in well-controlled patients