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Prevalence of nonsuppressed viral load and associated factors among HIV‐positive adults receiving antiretroviral therapy in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017): results from population‐based nationally representative surveys
Introduction The global target for 2020 is that ≥90% of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) will achieve viral load suppression (VLS). We examined VLS and its determinants among adults receiving ART for at least four months. Methods We analysed data from the population‐based HIV impact assessment (PHIA) surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017). PHIA surveys are nationally representative, cross‐sectional household surveys. Data collection included structured interviews, home‐based HIV testing and laboratory testing. Blood samples from PLHIV were analysed for HIV RNA, CD4 counts and recent exposure to antiretroviral drugs (ARVs). We calculated representative estimates for the prevalence of VLS (viral load <1000 copies/mL), nonsuppressed viral load (NVL; viral load ≥1000 copies/mL), virologic failure (VF; ARVs present and viral load ≥1000 copies/mL), interrupted ART (ARVs absent and viral load ≥1000 copies/mL) and rates of switching to second‐line ART (protease inhibitors present) among PLHIV aged 15 to 59 years who participated in the PHIA surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe, initiated ART at least four months before the survey and were receiving ART at the time of the survey (according to self‐report or ARV testing). We calculated odds ratios and incidence rate ratios for factors associated with NVL, VF, interrupted ART, and switching to second‐line ART. Results We included 9200 adults receiving ART of whom 88.8% had VLS and 11.2% had NVL including 8.2% who experienced VF and 3.0% who interrupted ART. Younger age, male sex, less education, suboptimal adherence, receiving nevirapine, HIV non‐disclosure, never having married and residing in Zimbabwe, Lesotho or Zambia were associated with higher odds of NVL. Among people with NVL, marriage, female sex, shorter ART duration, higher CD4 count and alcohol use were associated with lower odds for VF and higher odds for interrupted ART. Many people with VF (44.8%) had CD4 counts <200 cells/µL, but few (0.31% per year) switched to second‐line ART. Conclusions Countries are approaching global VLS targets for adults. Treatment support, in particular for younger adults, and people with higher CD4 counts, and switching of people to protease inhibitor‐ or integrase inhibitor‐based regimens may further reduce NVL prevalence.
Journal Article
Understanding victory : naval operations from Trafalgar to the Falklands
\"Using four warship-centered examples, this book shows how naval battles are won or lost--and how technological advantage is rarely as decisive in defeat or victory as is often claimed\"-- Provided by publisher.
Book
Third‐line antiretroviral therapy, including raltegravir (RAL), darunavir (DRV/r) and/or etravirine (ETR), is well tolerated and achieves durable virologic suppression over 144 weeks in resource‐limited settings: ACTG A5288 strategy trial
Introduction ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second‐line protease inhibitor (PI)‐based antiretroviral therapy (ART) from 10 low‐ and middle‐income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third‐line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV‐1 RNA ≤200 copies/ml. We report here long‐term outcomes over 144 weeks. Methods Study participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. “Extended Follow‐up” of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow‐up of ≥144 weeks), with HIV‐1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow‐up. Proportion of participants with HIV‐1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow‐up; mean CD4 count changes were estimated using loess regression. Results and Discussion Of 257 participants (38% females), at study entry, median CD4 count was 179 cells/mm3, and HIV‐1 RNA was 4.6 log10 copies/ml. Median follow‐up was 168 weeks (IQR: 156–204); 15 (6%) participants were lost to follow‐up and 9 (4%) died. 27/246 (11%), 26/246 (11%) and 13/92 (14%) of participants who started RAL, DRV/r and ETR, respectively, discontinued these drugs; only three due to adverse events. 87%, 86%, 83% and 80% of the participants had HIV‐1 RNA ≤200 copies/ml at weeks 48, 96, 144 and 168 (95% CI at week 168: 74–85%), respectively. Mean increase from study entry in CD4 count at week 168 was 265 cells/mm3 (95% CI 247–283). Conclusions Third‐line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second‐line PI‐based ART prior to the availability of dolutegravir.
Journal Article
Magnitude and correlates of virological failure among adult HIV patients receiving PI based second line ART regimens in north western Tanzania; a case control study
Background
With a growing access to free ART, switching of ART to second line regimen has also become common following failure of first line ART regimens. Patients failing on first line ART regimens have been shown to stand a high risk of failing on subsequent second line ART regimens. The magnitude of those who are failing virologicaly on second line ART is not documented in our setting. This study was designed to assess the magnitude and correlates of second line ART treatment failure.
Methods
A retrospective analysis of patients on second line ART for at least
1
year was done at Bugando care and treatment center. Information on demographic, clinical and laboratory data were collected and analyzed using STATA 11. The proportion of patients with Virological failure was calculated and potential correlates of virological failure were determined by logistic regression model.
Results
In total 197 patients on second line ART were included in this study and 24 (12.18%) of them met criteria for virological failure. The odds of having virological failure on second line ART were independently associated with age of less than 30 years (AOR = 12.5,
p
= 0.001), being on first line for less than 3 years (AOR = 6.1,
p
= 0.002) and CD4 at switch to second line ART of less than 200cells/μl (AOR = 16.3,
p
< 0.001).
Conclusion
Virological failure among patients on second line ART is common. Predictors of virological failure in this study could assist in planning for strategies to improve the outcome of this subgroup of patients including close clinical follow up of patients at risk, a continued adherence intensification and a targeted resistance testing before switching to second line ART.
Journal Article
Virological failure on first-line antiretroviral therapy; associated factors and a pragmatic approach for switching to second line therapy evidence from a prospective cohort study in rural South-Western Uganda, 2004-2011
We investigated factors affecting Virological failure (VF) on first line Antiretroviral Therapy (ART) and evaluated a pragmatic approach to switching to second line ART.
Between 2004 and 2011, we assessed adults taking ART. After 6 months or more on ART, participants with VL >1000 copies/ml or two successive VL > 400 copies/ml (Conventional VF) received intensified adherence counselling and continued on first-line ART for 6 more months, after which participants who still had VL > 1000 copies/ml (Pragmatic VF) were switched to second line ART. VF rates were calculated and predictors of failure were found by fitting logistic regression and Cox proportional hazards models.
The 316 participants accrued 1036 person years at risk (pyar), 84 (26.6%) had conventional VF (rate 8.6 per 100 pyar) of whom 28 (33.3%) had pragmatic VF (rate 2.7 per 100 pyar). Independent predictors of conventional VF were; alcohol consumption, (adjusted Hazard Ratio; aHR = 1.71, 95% CI 1.05-2.79, P = 0.03) and ART adherence: per 10% decrease in proportion of adherent visits, (aHR = 1.83, 95% CI 1.50-2.23; P < 0.001). Using reference age group < 30 years, among conventional failures, the adjusted odds ratio (aOR) of pragmatic failure for age group 30-39 years were 0.12, 95% CI 0.03-0.57, P = 0.02 and for age group > 40 years were 0.14, 95%CI 0.03-0.71, P = 0.02. Alcohol consumers had a threefold odds of pragmatic failure than non-alcohol consumers (aOR = 3.14, 95%CI 0.95-10.34, P = 0.06).
A pragmatic VF approach is essential to guide switching to second line ART. Patient tailored ART adherence counselling among young patients and alcohol users is recommended.
Journal Article
Simple line drawings suffice for functional MRI decoding of natural scene categories
Humans are remarkably efficient at categorizing natural scenes. In fact, scene categories can be decoded from functional MRI (fMRI) data throughout the ventral visual cortex, including the primary visual cortex, the parahippocampal place area (PPA), and the retrosplenial cortex (RSC). Here we ask whether, and where, we can still decode scene category if we reduce the scenes to mere lines. We collected fMRI data while participants viewed photographs and line drawings of beaches, city streets, forests, highways, mountains, and offices. Despite the marked difference in scene statistics, we were able to decode scene category from fMRI data for line drawings just as well as from activity for color photographs, in primary visual cortex through PPA and RSC. Even more remarkably, in PPA and RSC, error patterns for decoding from line drawings were very similar to those from color photographs. These data suggest that, in these regions, the information used to distinguish scene category is similar for line drawings and photographs. To determine the relative contributions of local and global structure to the human ability to categorize scenes, we selectively removed long or short contours from the line drawings. In a category-matching task, participants performed significantly worse when long contours were removed than when short contours were removed. We conclude that global scene structure, which is preserved in line drawings, plays an integral part in representing scene categories.
Journal Article
Emergence of HIV Drug Resistance During First- and Second-Line Antiretroviral Therapy in Resource-Limited Settings
Introduction. Antiretroviral therapy (ART) in resource-limited settings has expanded in the last decade, reaching >8 million individuals and reducing AIDS mortality and morbidity. Continued success of ART programs will require understanding the emergence of HIV drug resistance patterns among individuals in whom treatment has failed and managing ART from both an individual and public health perspective. We review data on the emergence of HIV drug resistance among individuals in whom first-line therapy has failed and clinical and resistance outcomes of those receiving second-line therapy in resource-limited settings. Results. Resistance surveys among patients initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)—based therapy suggest that 76%—90% of living patients achieve HIV RNA suppression by 12 months after ART initiation. Among patients with detectable HIV RNA at 12 months, HIV drug resistance, primarily due to M184V and NNRTI mutations, has been identified in 60%—72%, although the antiretroviral activity of proposed second-line regimens has been preserved. Complex mutation patterns, including thymidine-analog mutations, K65R, and multinucleoside mutations, are prevalent among cases of treatment failure identified by clinical or immunologic methods. Approximately 22% of patients receiving second-line therapy do not achieve HIV RNA suppression by 6 months, with poor adherence, rather than HIV drug resistance, driving most failures. Major protease inhibitor resistance at the time of second-line failure ranges from 0% to 50%, but studies are limited. Conclusions. Resistance of HIV to first-line therapy is predictable at 12 months when evaluated by means of HIV RNA monitoring and, when detected, largely preserves second-line therapy options. Optimizing adherence, performing resistance surveillance, and improving treatment monitoring are critical for long-term prevention of drug resistance.
Journal Article
Statistical analysis on the incidence and predictors of death among second-line ART patients in public hospitals of North Wollo and Waghemira Zones, Ethiopia, 2021
Acquired immune deficiency virus, caused by the human immunodeficiency virus, is a significant global health concern. Sub-Saharan Africa particularly Ethiopia faces a high prevalence of human immunodeficiency virus. In low-income settings like Ethiopia, early mortality rates are elevated due to severe opportunistic infections and advanced disease at Anti-retroviral treatment initiation. Despite available treatments, delayed treatment initiation among Human Immunodeficiency Virus -infected individuals in Africa, including Ethiopia, leads to disease progression and increased mortality risk. This study aimed to identify the factors contributing to the death of HIV patients under treatment at second line regimen in public hospitals of North Wollo and Waghemira Zones. A retrospective cohort study with 474 patients was conducted in selected hospitals of North Wollo and Waghemira Zones. A parametric Weibull regression model was employed, and the adjusted hazard ratio served as the measure of association. Variables significantly affected the outcome of the study was determined at a p-value < 0.05, along with a 95% confidence interval for the variables. The patients were within the average age of 38.6(standard deviation ± 12.5) years and majority (45.57%) had no formal education. The overall death incidence rate among second-line anti-retroviral treatment patients was 1.98 per 100-person years [95% CI 1.4—2.9%]. Poor adherence to antiretroviral treatment, male gender, and being underweight significantly increased the hazard of death. Conversely, increased anti-retroviral treatment duration had a significant and negative impact, reducing the hazard of death among patients. The study reveals a high incidence of death among second line anti-retroviral treatment users. Independent predictors include poor adherence, male gender, and underweight status, all significantly increasing the risk of death. On the positive side, the hazard of death decreases with longer anti-retroviral treatment duration. A critical concern and counseling should be given for better ART adherence, to change their nutritional status and for males.
Journal Article
Magnitude and factors associated with virological failure among adults on first-line antiretroviral therapy in Dire Dawa, eastern Ethiopia: a retrospective chart review
Background
First-line antiretroviral therapy failure reduces the benefits of the antiretroviral therapy (ART) program and could lead to regimen change to a more expensive second-line ART. To identify ART failure, routine viral load monitoring is recommended as the gold standard and has been implemented in Ethiopia since 2017. However, evidence regarding the virological failure of the first-line ART is limited in the study setting, Dire Dawa Ethiopia.
Objective
This study aimed to determine the magnitude and factors associated with virological treatment failure among adults on first-line ART follow-up in Dire Dawa between January 2017 and December 2019.
Methods
A retrospective chart review was conducted among 272 randomly selected adults on first-line ART follow-up, between January 2017 to December 2019. Data were collected from patients’ medical records, entered into epi data version 3.02 and exported to Stata version 15 software for analysis. A bivariable and multivariable binary logistic regression model was used to identify factors associated with virological first-line ART failure. The goodness of fit of the model was assessed using the Hosmer–Lemeshow test. All statistical tests are declared significant at a
P
-value of < 0.05.
Results
A total of 257 ART patients’ records were included for final analysis. The magnitude of first-line ART virological failure was 11.28% (95% CI 7.69, 15.80). Baseline undernutritional status (AOR = 3.72: 1.05, 13.14), serostatus nondisclosure (AOR = 4.45: 1.34, 14.79), early (≤ 30 days) ART initiation (AOR = 0.235: 0.064, 0.859), history of missed any daily ART dose (AOR = 3.16: 1.01, 9.89) and dolutegravir-based regimen (AOR = 0.28: 0. 09, 0.90) were significantly associated with virological failure of first-line ART.
Conclusion
The magnitude of virological first-line ART failure in this study was relatively high. Virological first-line ART failure was significantly associated with baseline BMI, HIV serostatus disclosure, duration of ART initiation after HIV diagnosis, history of missed ART doses, and substitution of DTG-based ART first-line regimens. To avoid treatment failure, it is crucial to disclose one's serostatus, encourage adherence initiatives, and early initiation of ART preferably a dolutegravir-based regimen.
Journal Article