Clinical outcomes after first‐line HIV treatment failure in South Africa: the next cascade of care

Among those with HIV, anemia is a strong risk factor for disease progression and death independent of CD4 count and viral load. Understanding the role of anemia in HIV treatment is critical to developing strategies to reduce morbidity and mortality. We conducted a prospective analysis among 10,259 HIV-infected adults initiating first-line ART between April 2004 and August 2009 in Johannesburg, South Africa. The prevalence of anemia at ART initiation was 25.8%. Mean hemoglobin increased independent of baseline CD4. Females, lower BMI, WHO stage III/IV, lower CD4 count, and zidovudine use were associated with increased risk of developing anemia during follow-up. After initiation of ART, hemoglobin improved, regardless of regimen type and the degree of immunosuppression. Between 0 and 6 months on ART, the magnitude of hemoglobin increase was linearly related to CD4 count. However, between 6 and 24 months on ART, hemoglobin levels showed a sustained overall increase, the magnitude of which was similar regardless of baseline CD4 level. This increase in hemoglobin was seen even among patients on zidovudine containing regimens. Since low hemoglobin is an established adverse prognostic marker, prompt identification of anemia may result in improved morbidity and mortality of patients initiating ART.

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High-Levels of Acquired Drug Resistance in Adult Patients Failing First-Line Antiretroviral Therapy in a Rural HIV Treatment Programme in KwaZulu-Natal, South Africa

PLoS ONE ◽

10.1371/journal.pone.0072152 ◽

2013 ◽

Vol 8 (8) ◽

pp. e72152 ◽

Cited By ~ 36

Author(s):

Justen Manasa ◽

Richard J. Lessells ◽

Andrew Skingsley ◽

Kevindra K. Naidu ◽

Marie-Louise Newell ◽

...

Keyword(s):

South Africa ◽

Drug Resistance ◽

Antiretroviral Therapy ◽

Hiv Treatment ◽

Adult Patients ◽

Treatment Programme ◽

First Line ◽

Acquired Drug Resistance ◽

Kwazulu Natal

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Medication Side Effects and Retention in HIV Treatment: A Regression Discontinuity Study of Tenofovir Implementation in South Africa and Zambia

American Journal of Epidemiology ◽

10.1093/aje/kwy093 ◽

2018 ◽

Vol 187 (9) ◽

pp. 1990-2001 ◽

Cited By ~ 3

Author(s):

Alana T Brennan ◽

Jacob Bor ◽

Mary-Ann Davies ◽

Gilles Wandeler ◽

Hans Prozesky ◽

...

Keyword(s):

South Africa ◽

Relative Risk ◽

Side Effects ◽

Regression Discontinuity ◽

Retention In Care ◽

Hiv Treatment ◽

Local Linear Regression ◽

First Line ◽

Percentage Points ◽

The Impact

Abstract Tenofovir is less toxic than other nucleoside reverse-transcriptase inhibitors used in antiretroviral therapy (ART) and may improve retention of human immunodeficiency virus (HIV)–infected patients on ART. We assessed the impact of national guideline changes in South Africa (2010) and Zambia (2007) recommending tenofovir for first-line ART. We applied regression discontinuity in a prospective cohort study of 52,294 HIV-infected adults initiating first-line ART within 12 months (±12 months) of each guideline change. We compared outcomes in patients presenting just before and after the guideline changes using local linear regression and estimated intention-to-treat effects on initiation of tenofovir, retention in care, and other treatment outcomes at 24 months. We assessed complier causal effects among patients starting tenofovir. The new guidelines increased the percentages of patients initiating tenofovir in South Africa (risk difference (RD) = 81 percentage points, 95% confidence interval (CI): 73, 89) and Zambia (RD = 42 percentage points, 95% CI: 38, 45). With the guideline change, the percentage of single-drug substitutions decreased substantially in South Africa (RD = −15 percentage points, 95% CI: −18, −12). Starting tenofovir also reduced attrition in Zambia (intent-to-treat RD = −1.8% (95% CI: −3.5, −0.1); complier relative risk = 0.74) but not in South Africa (RD = −0.9% (95% CI: −5.9, 4.1); complier relative risk = 0.94). These results highlight the importance of reducing side effects for increasing retention in care, as well as the differences in population impact of policies with heterogeneous treatment effects implemented in different contexts.

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Impact of Cefazolin Shortage on Clinical Outcomes of Adult Patients with Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus in a Tertiary Care University Hospital

Antibiotics ◽

10.3390/antibiotics10101247 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1247

Author(s):

Atsushi Uda ◽

Kenichiro Onuma ◽

Katsumi Shigemura ◽

Koichi Kitagawa ◽

Yonmin Yan ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Treatment Failure ◽

Clinical Outcomes ◽

Tertiary Care ◽

Demographic Characteristics ◽

University Hospital ◽

Drug Reactions ◽

First Line ◽

Definitive Therapy ◽

The Impact

Cefazolin is an essential antibiotic used for treating bacteremia; in particular, it is recommended as a first-line agent for infections caused by methicillin-susceptible Staphylococcus aureus (MSSA). In March 2019, problems with a major antibiotic supplier caused a critical shortage of cefazolin in Japan; however, the impact of the cefazolin shortage on clinical outcomes remains unknown. This study aimed to evaluate the effect of the cefazolin shortage in patients with MSSA bacteremia. Data from 75 patients were compared between the pre-shortage (March 2018–January 2019, n = 39) and post-shortage (March 2019–January 2020, n = 36) periods. There were no significant differences in the demographic characteristics between the two groups, and the cefazolin shortage did not worsen clinical outcomes such as adverse drug reactions, treatment failure, and 30-day mortality. In the post-shortage group, ampicillin/sulbactam and benzylpenicillin were more frequently administered as alternative antibiotics for empirical and definitive therapy (10% vs. 31%, p = 0.042; 0% vs. 19%, p = 0.004, respectively). Multivariate analysis revealed that the broad-spectrum antibiotics for definitive therapy, such as antipseudomonal penicillin, were associated with treatment failure in patients with MSSA bacteremia (OR = 17, p = 0.003). Hence, narrow-spectrum antibiotics should be prescribed for MSSA bacteremia as alternatives during a cefazolin shortage.

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Acquired HIV drug resistance and virologic monitoring in a HIV hyper-endemic setting in KwaZulu-Natal Province, South Africa

AIDS Research and Therapy ◽

10.1186/s12981-021-00393-5 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Benjamin Chimukangara ◽

Richard J. Lessells ◽

Lavanya Singh ◽

Indra Grigalionyte ◽

Nonhlanhla Yende-Zuma ◽

...

Keyword(s):

South Africa ◽

Drug Resistance ◽

Sequence Data ◽

Hiv Treatment ◽

Close Monitoring ◽

Second Line ◽

First Line ◽

Treatment Regimens ◽

Kwazulu Natal ◽

Hiv 1

Abstract Background Introduction of tenofovir (TDF) plus lamivudine (3TC) and dolutegravir (DTG) in first- and second-line HIV treatment regimens in South Africa warrants characterization of acquired HIV-1 drug resistance (ADR) mutations that could impact DTG-based antiretroviral therapy (ART). In this study, we sought to determine prevalence of ADR mutations and their potential impact on susceptibility to drugs used in combination with DTG among HIV-positive adults (≥ 18 years) accessing routine care at a selected ART facility in KwaZulu-Natal, South Africa. Methods We enrolled adult participants in a cross-sectional study between May and September 2019. Eligible participants had a most recent documented viral load (VL) ≥ 1000 copies/mL after at least 6 months on ART. We genotyped HIV-1 reverse transcriptase and protease genes by Sanger sequencing and assessed ADR. We characterized the effect of ADR mutations on the predicted susceptibility to drugs used in combination with DTG. Results From 143 participants enrolled, we obtained sequence data for 115 (80%), and 92.2% (95% CI 85.7–96.4) had ADR. The proportion with ADR was similar for participants on first-line ART (65/70, 92.9%, 95% CI 84.1–97.6) and those on second-line ART (40/44, 90.9%, 95% CI 78.3–97.5), and was present for the single participant on third-line ART. Approximately 89% (62/70) of those on first-line ART had dual class NRTI and NNRTI resistance and only six (13.6%) of those on second-line ART had major PI mutations. Most participants (82%) with first-line viraemia maintained susceptibility to Zidovudine (AZT), and the majority of them had lost susceptibility to TDF (71%) and 3TC (84%). Approximately two in every five TDF-treated individuals had thymidine analogue mutations (TAMs). Conclusions Susceptibility to AZT among most participants with first-line viraemia suggests that a new second-line regimen of AZT + 3TC + DTG could be effective. However, atypical occurrence of TAMs in TDF-treated individuals suggests a less effective AZT + 3TC + DTG regimen in a subpopulation of patients. As most patients with first-line viraemia had at least low-level resistance to TDF and 3TC, identifying viraemia before switch to TDF + 3TC + DTG is important to avoid DTG functional monotherapy. These findings highlight a need for close monitoring of outcomes on new standardized treatment regimens.

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Free but fragile: Human relations amidst poverty and HIV in democratic South Africa

Oral History Journal of South Africa ◽

10.25159/2309-5792/8 ◽

2015 ◽

Vol 2 (2) ◽

pp. 85-94

Author(s):

Christina Landman

Keyword(s):

South Africa ◽

Predominantly White ◽

Black People ◽

Hiv Treatment ◽

Human Relations ◽

White People ◽

Black And White ◽

The Past ◽

Wide Range ◽

Black Township

Dullstroom-Emnotweni is the highest town in South Africa. Cold and misty, it is situated in the eastern Highveld, halfway between the capital Pretoria/Tswane and the Mozambique border. Alongside the main road of the white town, 27 restaurants provide entertainment to tourists on their way to Mozambique or the Kruger National Park. The inhabitants of the black township, Sakhelwe, are remnants of the Southern Ndebele who have lost their land a century ago in wars against the whites. They are mainly dependent on employment as cleaners and waitresses in the still predominantly white town. Three white people from the white town and three black people from the township have been interviewed on their views whether democracy has brought changes to this society during the past 20 years. Answers cover a wide range of views. Gratitude is expressed that women are now safer and HIV treatment available. However, unemployment and poverty persist in a community that nevertheless shows resilience and feeds on hope. While the first part of this article relates the interviews, the final part identifies from them the discourses that keep the black and white communities from forming a group identity that is based on equality and human dignity as the values of democracy.

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Assessing first-line treatments and associated clinical outcomes among hospitalized patients with nosocomial pneumonia (NP) based on interim analysis in Europe and Russia of the RECOMMEND Study

10.26226/morressier.56d5ba26d462b80296c94b86 ◽

2016 ◽

Author(s):

Sudeep Karve

Keyword(s):

Clinical Outcomes ◽

Nosocomial Pneumonia ◽

Interim Analysis ◽

Hospitalized Patients ◽

First Line

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Effect of Obesity on Clinical Failure of Patients Treated with Beta-Lactams

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab212 ◽

2021 ◽

Author(s):

Nathan A Pinner ◽

Natalie G Tapley ◽

Katie E Barber ◽

Kayla R Stover ◽

Jamie L Wagner

Keyword(s):

Treatment Failure ◽

Clinical Outcomes ◽

Hospital Length Of Stay ◽

Source Control ◽

Definitive Treatment ◽

Therapeutic Drug ◽

Obese Patients ◽

Definitive Therapy ◽

All Cause Mortality ◽

The Impact

Abstract Background Altered pharmacokinetics in obese patients raise concerns over worse clinical outcomes. This study assessed whether obese patients receiving a beta-lactam (BL) have worse clinical outcomes compared to non-obese patients and to identify if therapeutic drug monitoring (TDM) may be beneficial. Methods This multi-center, retrospective cohort included hospitalized adults admitted from July 2015-July 2017 treated with a BL as definitive monotherapy against a Gram-negative bacilli for ≥72 hours. Patients were excluded if there was lack of source control or if polymicrobial infections required >1 antibiotic for definitive therapy. Patients were classified based on body mass index (BMI): non-obese (BMI ≤29.9 kg/m 2) and obese (BMI ≥30.0 kg/m 2). The primary outcome was clinical treatment failure, and secondary were hospital length of stay (LOS), inpatient all-cause mortality, and 30-day all-cause readmission. Results There were 257 (43.6%) obese patients and 332 (56.4%) non-obese patients included. The most common infections were urinary (50.9%) and respiratory (31.4%). Definitive treatment was driven by 3 rd generation cephalosporins (46.9%) and cefepime (44.7%). Treatment failure occurred in 131 (51%) obese patients and 109 (32.8%) non-obese patients (p<0.001). Obesity and respiratory source were independently associated with increased likelihood of treatment failure. Obese patients were hospitalized longer than non-obese patients (p=0.002), but no differences were found for all-cause mortality (p=0.117) or infection-related readmission (0=0.112). Conclusions Obese patients treated with BLs have higher rates of treatment failure and longer hospitalization periods than non-obese patients. Future studies are needed to assess the impact of TDM and specific dosing recommendations for targeted infection types.

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