Low-cost dynabead and cytospheres compared to FACSCount to monitor patients on antiretroviral therapy at a public clinic in Kampala, Uganda

BackgroundSouth Africa implemented universal test and treat (UTT) in September 2016 in an effort to encourage earlier initiation of antiretroviral therapy (ART).MethodsWe therefore conducted an interrupted time series (ITS) analysis to assess the impact of UTT on mean CD4 count at ART initiation among adults aged ≥16 years attending 17 public sector primary care clinics in rural South Africa, between July 2014 and March 2019.ResultsAmong 20 599 individuals (69% women), CD4 counts were available for 74%. Mean CD4 at ART initiation increased from 317.1 cells/μL (95% confidence interval [CI], 308.6 to 325.6) 1 to 8 months prior to UTT to 421.0 cells/μL (95% CI, 413.0 to 429.0) 1 to 12 months after UTT, including an immediate increase of 124.2 cells/μL (95% CI, 102.2 to 146.1). However, mean CD4 count subsequently fell to 389.5 cells/μL (95% CI, 381.8 to 397.1) 13 to 30 months after UTT but remained above pre-UTT levels. Men initiated ART at lower CD4 counts than women (–118.2 cells/μL, 95% CI, –125.5 to –111.0) throughout the study.ConclusionsAlthough UTT led to an immediate increase in CD4 count at ART initiation in this rural community, the long-term effects were modest. More efforts are needed to increase initiation of ART early in those living with human immunodeficiency virus, particularly men.

Backgrounds: As there is no published data regarding the response to Anti-retroviral therapy (ART) among HIV patients from Bangladesh. The present study was designed to determine the immunological and virological responses of HIV infected Bangladeshi adults starting ART. Objectives: To monitor the changes of CD4 and CD8 T-lymphocyte count and Viral load (VL) before and after three and six months of starting ART.Methods: 20 symptomatic HIV infected patients with CD4 T-lymphocyte count of <350 cells/µ] of blood were initiated ART.CD4 and CDS T-lymphocyte counts were estimated by Flowcytometer and VL was dete1mined by real-time PCR technique.Results: The mean CD4 T-lymphocyte count among the sn1dy patients were 177±127 cells/µl before initiation of ART. After ART initiation, their mean CD4 count increased significantly to 368±181 and 452±183 cellshll after three and six months respectively (P<0.0001).The mean CDS T-lymphocyte counts were 901±650 cells/µ! before initiation of ART, which increased to I 085±393 and 1121±372 cells/µl after three and six months respectively after ART initiation (P>0.05). Before ART initiation, the mean VL was 5.25±1.19 log10 (copies/ml) among the study population which became undetectable in 15 (75%) patients after three months of ART and in another 2 (10%) patients after 6 months of ART initiation.Conclusion: Our study concluded that, ART is effective in slowing the progression of HIV infection to AIDS with good immunological and virological outcome among the ART initiators.

BackgroundPersons living with HIV (PLHIV) receiving antiretroviral therapy (ART) have a high prevalence of hypertension (HTN) and increased risk of mortality from cardiovascular diseases. HTN and HIV care integration is recommended in Uganda, though its implementation has lagged. In this study, we sought to analyze the HTN and HIV care cascades and explore barriers and facilitators of HTN/HIV integration within a large HIV clinic in urban Uganda.MethodsWe conducted an explanatory sequential mixed methods study at Mulago ISS clinic in Kampala, Uganda. We determined proportions of patients in HTN and HIV care cascade steps of screened, diagnosed, initiated on treatment, retained, and controlled. Guided by the Capability, Opportunity, Motivation and Behavior (COM-B) model, we then conducted semi-structured interviews and focus group discussions with healthcare providers (n = 13) and hypertensive PLHIV (n = 32). We coded the qualitative data deductively and analyzed the data thematically categorizing them as themes that influenced HTN care positively or negatively. These denoted barriers and facilitators, respectively.ResultsOf 15,953 adult PLHIV, 99.1% were initiated on ART, 89.5% were retained in care, and 98.0% achieved control (viral suppression) at 1 year. All 15,953 (100%) participants were screened for HTN, of whom 24.3% had HTN. HTN treatment initiation, 1-year retention, and control were low at 1.0%, 15.4%, and 5.0%, respectively. Barriers and facilitators of HTN/HIV integration appeared in all three COM-B domains. Barriers included low patient knowledge of HTN complications, less priority by patients for HTN treatment compared to ART, sub-optimal provider knowledge of HTN treatment, lack of HTN treatment protocols, inadequate supply of anti-hypertensive medicines, and lack of HTN care performance targets. Facilitators included patients’ and providers’ interest in HTN/HIV integration, patients’ interest in PLHIV peer support, providers’ knowledge and skills for HTN screening, optimal ART adherence counseling, and availability of automated BP machines.ConclusionThe prevalence of HTN among PLHIV is high, but the HTN care cascade is sub-optimal in this successful HIV clinic. To close these gaps, models of integrated HTN/HIV care are urgently needed. These findings provide a basis for designing contextually appropriate interventions for HTN/HIV integration in Uganda and other low- and middle-income countries.

BackgroundLong-term virologic data of children receiving antiretroviral therapy (ART) in India are limited. We examined the long-term virologic outcome of a pediatric cohort on non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART in south India.MethodsPerinatally HIV infected children, between 2–12 years of age initiating NNRTI-based ART during 2010–2014 and with at least 12 months of follow-up, were included in analysis. CD4 cell counts and viral load measurements were performed at 24 and 48 weeks. Immunologic Failure (IF) was defined as decrease in CD4 count of > 30% from baseline; immunologic recovery (IR) as an increase in CD4 count of >25% from baseline while Virologic Failure (VF) was defined as HIV-RNA of >1,000 copies/ml at 48 weeks after ART initiation. Genotypic resistance testing was performed for children with VF. Logistic regression analysis was used to determine predictors of VFResultsA total of 378 ART-naïve HIV infected children with mean age: 7.6 + 3 years, mean CD4%: 16% (8) and median HIV-RNA: 5.1 (3.5 – 5.7) log10 copies/ml, were enrolled. 74 % were started on nevirapine and 24% on efavirenz-based ART.At 48 weeks, 331 of 378 (88%) children completed follow-up, 15 died, 3 transferred out and 29 were lost to follow up. Significant improvement occurred in weight-for-age and height-for-age z-scores from baseline (all P < 0.001). 79% of children showed IR. VF was seen in 29% (94 / 328), while IF was seen in only 3% (10 / 331) of children. 62% of children with VF reported >90% adherence to ART. Of the 94 children with VF, 5 children showed IF. Correlation between VF and IF was absent. Sensitivity (95% CI) of IF to VF was 6% (2.2–14.6), specificity 98% (94.9–99.5), PPV 56% (26.7–81.1) and NPV was 73.4% (67.8–78.4). At the time of VF, multiple NNRTI-associated mutations were observed in 80% (52/65) of children - K103N and Y181C were the major NNRTI DRMs onserved. M184V also was observed in 79% of children with VF. No definite predictors of VF could be determined.ConclusionThough ART provides significant benefit to children in India, over a quarter of them had VF and developed major drug-resistance mutations after 48 weeks of ART. There is a lack of correlation between IF and VF, leading to delay in identifying treatment failure. Periodic plasma HIV-RNA testing should be performed to detect treatment failures early.DisclosuresAll authors: No reported disclosures.

BackgroundMany HIV-infected children in sub-Saharan Africa reside in rural areas, yet most research on treatment outcomes has been conducted in urban centers. Rural clinics and residents may face unique barriers to care and treatment.MethodsA prospective cohort study of HIV-infected children was conducted between September 2007 and September 2010 at the rural HIV clinic in Macha, Zambia. HIV-infected children younger than 16 years of age at study enrollment who received antiretroviral therapy (ART) during the study were eligible. Treatment outcomes during the first two years of ART, including mortality, immunologic status, and virologic suppression, were assessed and risk factors for mortality and virologic suppression were evaluated.ResultsA total of 69 children entered the study receiving ART and 198 initiated ART after study enrollment. The cumulative probabilities of death among children starting ART after study enrollment were 9.0% and 14.4% at 6 and 24 months after ART initiation. Younger age, higher viral load, lower CD4+ T-cell percentage and lower weight-for-age z-scores at ART initiation were associated with higher risk of mortality. The mean CD4+ T-cell percentage increased from 16.3% at treatment initiation to 29.3% and 35.0% at 6 and 24 months. The proportion of children with undetectable viral load increased to 88.5% and 77.8% at 6 and 24 months. Children with longer travel times (≥5 hours) and those taking nevirapine at ART initiation, as well as children who were non-adherent, were less likely to achieve virologic suppression after 6 months of ART.ConclusionsHIV-infected children receiving treatment in a rural clinic experienced sustained immunologic and virologic improvements. Children with longer travel times were less likely to achieve virologic suppression, supporting the need for decentralized models of ART delivery.

The effect of coenzyme Q10 in comparison with placebo on CD4 in HIV-infected patients

To investigate whether an unrecognised diagnosis of tuberculosis (TB) at the start of antiretroviral therapy (ART) influences subsequent CD4+ T cell (CD4) count recovery in an urban HIV clinic in Uganda. In a retrospective cohort study, a multivariable polynomial mixed effects model was used to estimate CD4 recovery in the first 96 weeks of ART in two groups of patients: prevalent TB (started ART while on TB treatment), unrecognised TB (developed TB within 6 months after start ART). Included were 511 patients with a median baseline CD4 count of 57 cells/mm(3) (interquartile range: 22-130), of whom 368 (72%) had prevalent TB and 143 (28%) had unrecognised TB. Compared with prevalent TB, unrecognised TB was associated with lower CD4 count recovery at 96 weeks: -22.3 cells/mm(3) (95% confidence interval -43.2 to -1.5, P = 0.036). These estimates were adjusted for gender, age, baseline CD4 count and the use of zidovudine-based regimen. Unrecognised TB at the time of ART initiation resulted in impaired CD4 recovery compared with TB treated before ART initiation. More vigilant screening with more sensitive and rapid TB diagnostics prior to ART initiation is needed to decrease the risk of ART-associated TB and sub-optimal immune reconstitution.

An interlaboratory comparison study was conducted among five laboratories for determining 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) in human serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The Centers for Disease Control and Prevention (CDC), Imperial College Healthcare NHS Trust, University College Cork, University of Liège, and University of Washington analyzed 50 single-donor samples and two new Standard Reference Materials (SRMs®). The results from each laboratory were compared with target values assigned by the National Institute of Standards and Technology (NIST) using a reference measurement procedure (RMP) and evaluated using Ordinary Deming linear regression and Bland-Altman analysis. Three of the five laboratory methods provided results that were in good agreement with the NIST RMP results showing linear regression slopes ranging from 0.972 to 1.003 and Bland-Altman mean bias of -0.092nmol/L, 0.025nmol/L, and 0.035nmol/L. Two laboratories demonstrated a significant positive bias with linear regression slopes of 1.158 and 1.214 and Bland-Altman mean bias of 0.162nmol/L and 0.708nmol/L. The CDC method is currently used to assign "information only" values for 24,25(OH)2D3 in the quarterly distributions of the Vitamin D External Quality Assessment Scheme (DEQAS). Given the agreement (linear regression slope = 0.984, R2 = 0.996 and mean bias of -0.092nmol/L) between the CDC method and the NIST RMP observed in this study, the CDC-assigned 24,25(OH)2D3 values in DEQAS may provide a more accurate reference than the current participant consensus mean values.

There is a paucity of data on clinical epidemiology of osteonecrosis in HIV-infected patients. We aimed to describe patients' characteristics and natural history of this poorly known condition. All cases of symptomatic HIV-related osteonecrosis diagnosed from 1990 through 2003 in 19 Spanish clinics were reviewed. Functional status at the last visit was assessed with the validated Western Ontario and McMaster Universities Index questionnaire. Of 54 patients analyzed, 29 (53.7%) had a single bone necrosis, and 25 (46.3%) had 2 or more sites involved. Progression of symptoms happened more often in patients with hip involvement (17/39 vs 0/8 patients; P = 0.019). Twenty patients (37%) required surgical intervention. Male sex and higher CD4 cell count were associated with surgery on multivariable analysis. Overall, at the end of the follow-up period, half of the patients had moderate to severe disability (Western Ontario and McMaster Universities Index score > or =60). During a follow-up period of 137 person-years, only 2 new episodes of osteonecrosis were observed (rate of recurrences, 1.5/100 person-years; 95% confidence interval, 0.4-5.1). HIV-related osteonecrosis is associated with significant disability over time. Location of bone necrosis, sex, and CD4 cell count may influence the outcome. The risk for recurrences for patients who have experienced 1 episode is low.

The International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1060 study demonstrated short-term superiority of lopinavir/ritonavir (LPV/r) over nevirapine (NVP) in antiretroviral therapy (ART), regardless of prior NVP exposure. However, NVP-based ART had a marginal benefit in CD4 percentage (CD4%) and growth. We compared 5-year outcomes from this clinical trial. Human immunodeficiency virus (HIV)-infected, ART-eligible children were enrolled into 2 cohorts based on prior NVP exposure and randomized to NVP- or LPV/r-based ART. The data safety monitoring board recommended unblinding results in both cohorts due to superiority of LPV/r for the primary endpoint: stopping randomized treatment, virologic failure (VF), or death by 6 months. Participants were offered a switch in regimens (if on NVP) and continued observational follow-up. We compared time to VF or death, death, and CD4% and growth changes using intention-to-treat analyses. Additionally, inverse probability weights were used to account for treatment switching and censoring. As of September 2014, 329 of the 451 (73%) enrolled participants were still in follow-up (median, 5.3 years; interquartile range [IQR], 4.3-6.4), with 52% on NVP and 88% on LPV/r as originally randomized. NVP arm participants had significantly higher risk of VF or death (adjusted hazard ratio [aHR], 1.90; 95% confidence interval [CI], 1.37-2.65) but not death alone (aHR, 1.65; 95% CI, .72-3.76) compared with participants randomized to LPV/r. Mean CD4% was significantly higher in the NVP arm up to 1 year after ART initiation, but not beyond. Mean weight-for-age z scores were marginally higher in the NVP arm, but height-for-age z scores did not differ. Similar trends were observed in sensitivity analyses. These findings support the current World Health Organization recommendation of LPV/r in first-line ART regimens for HIV-infected children. NCT00307151.

BackgroundIn South Africa, women continue to face a high burden of Human Immunodeficiency Virus (HIV) infection and the possible complications thereof during pregnancy. We assessed pregnancy incidence rates and outcomes in a longitudinal HIV cohort study over a 15-year period.MethodsWe evaluated pregnancies among women ≥ 18 years between 2004 and 2019 in the CAPRISA 002 study. We analysed pregnancy rates following HIV acquisition, CD4 counts and HIV viral load dynamics and pregnancy outcomes. We used linear regression to assess if the mean CD4 and log10 viral load close to delivery increases or decreases linearly across three different timepoints.ResultsIn total 245 women enrolled into the HIV negative study phase, 225 into the HIV infection phase and 232 in the antiretroviral therapy (ART) phase. Median follow-up time was 2.0 years [Interquartile Range (IQR) 0.8–2.0] during the HIV negative phase, 2.6 years; (IQR) 1.2–4.8] during HIV infection and 3.7 years (IQR 1.8–5.0) on ART, with maximum follow-up time of 2, 10 and 6 years respectively. Overall, 169 pregnancies occurred in 140 women, of which 16 pregnancies were observed during acute or early HIV infection [Incidence Rate (IR) 8.0 per 100 women-years; 95% confidence interval (CI): 4.6—12.9], 48 during established infection [IR 9.3; (CI 6.8–12.3)] and 68 on ART [IR 8.9; (CI: 7.0 – 11.4)]. Birth outcomes from 155/169 (91.7%) pregnancies were 118 (76.1%) full term live births, 17 (10.9%) premature live births, 9 (5.8%) therapeutic/elective miscarriages, 8 (5.1%) spontaneous miscarriages and 3 (1.9%) spontaneous foetal deaths or stillbirths. Six mother-to-child transmission events occurred, with four documented prior to 2008. Over time, mean CD4 count in pregnant women increased from 395 cells/µL (2004—2009) to 543 cells/µL (2010–2014) and to 696 cells/µL (2015–2019), p < 0.001. Conversely, the viral load declined from 4.2 log10 copies/ml to 2.5 log10 copies/ml and to 1.2 log10 copies/ml (p < 0.001) for the corresponding periods.ConclusionsPregnancy rates following HIV acquisition were high, emphasising a need for timeous ART provision and contraception counselling in women recently diagnosed with HIV. CD4 count and HIV viral load trajectories reflect improvements in treatment guidance for pregnant women over time.

IntroductionGender differences in antiretroviral therapy (ART) outcomes are critical in sub-Saharan Africa. We assessed the association between gender and virologic failure among adult patients treated in a public routine clinic (one of the largest in West Africa) in Burkina Faso.MethodsWe performed a case-control study between July and October 2012 among patients who had received ART at the Bobo Dioulasso Day Care Unit. Patients were eligible if they were 15 years or older, positive for HIV-1 or HIV-1+2, and on first-line ART for at least six months. Cases were all patients with two consecutive HIV loads >1000 copies/mL (Biocentric Generic or Abbott Real Time assays), or one HIV load >1000 copies/mL associated with immunologic or clinical failure criteria. Controls were all patients who only had HIV loads <300 copies/mL. The association between gender and virologic failure was assessed using a multivariate logistic regression, adjusted on age, level of education, baseline CD4+ T cell count, first and current antiretroviral regimens and time on ART.ResultsOf 2303 patients (74.2% women; median age: 40 years; median time on ART: 34 months), 172 had virologic failure and 2131 had virologic success. Among the former, 130 (75.6%) had confirmed virologic failure, 38 (22.1%) had viro-immunologic failure, and four (2.3%) had viro-clinical failure. The proportion of men was significantly higher among the cases than among the controls (37.2% vs. 24.9%; p<0.001). Compared to controls, cases were also younger, more immunodeficient at ART initiation, less likely to receive a protease inhibitor-based antiretroviral regimen and had spent a longer period of time on ART. After adjustment, male gender remained strongly associated with virologic failure (odds ratio 2.52, 95% CI: 1.77–3.60; p<0.001).ConclusionsMen on ART appeared more vulnerable to virologic failure than women. Additional studies are needed to confirm the poorer prognosis of men in this setting and to determine the causes for their vulnerability in order to optimize HIV care. From now on, efforts should be made to support the adherence of men to ART in the African setting.

In immunodeficiency diseases such as Human Immunodeficiency Virus (HIV) infection, various body functions may be affected; visual function could be one of them. In a child, there are predictable adverse outcomes of the disease that bother physical and mental development. This study sought to investigate any potential compromise of visual function amongst HIV-infected children on anti-retroviral drugs known as Highly Active Antiretroviral Therapy (HAART) use by comparing the visual acuity, colour sense and field of vision in infected and non-infected children. One hundred (100) children aged between 5 to 15 years consisting of fifty (50) HIV infected and fifty (50) non-HIV infected were selected through random sampling. Visual acuity test (Snellen’s method), colour sense test (Ishihara chart method) and field of vision test (confrontational method) were carried out. Latest Cluster of Differentiation 4 (CD4+) count of the HIV infected subjects also was collected. Statistical analysis was carried out using the Student T Test and ANOVA. The mean visual acuity of Human Immunodeficiency Virus (HIV) infected children was slightly low compared to the negative group (94.2±4.61and 96.4±12.58 respectively) but was not statistically significant (p>0.05). The mean of Ishihara colour sense test and that of the field of vision test also showed no statistically significant change between infected and non-infected children. Mean CD4+ count of the HIV infected children increased with age and use of anti-retroviral drugs. From 11 to 15 years, percentage defect in visual acuity increased amongst the HIV infected children, compared to the other ages but not statistically significant (p>0.05). It was concluded that visual acuity decreases slightly with improving CD4+ count and increasing age, for HIV positive children on anti-retroviral drugs. These parameters could be observed in subsequent years and subjects monitored for further investigation.

Older people living with HIV (PLHIV) are at high risk of developing geriatric syndromes. Data on geriatric syndromes among older PLHIV in sub-Saharan Africa are scarce. We examined sex differences in the prevalence and correlates of geriatric syndromes among PLHIV aged ≥60 years on antiretroviral therapy in Kampala, Uganda. This cross-sectional study analyzed data obtained during the enrollment of older PLHIV into a prospective observational cohort in Kampala. We used the Poisson regression model to explore the association between the number of geriatric syndromes and non-communicable diseases (NCDs), sociodemographic factors, and HIV-related factors. We included 500 participants (48.8% women) with a median age of 64 years (interquartile range, IQR: 62.68). Almost all (94.4%) participants had at least one geriatric syndrome. More women were frail (13.1% vs 5.1%, P-value = 0.01) and had lower physical performance measured using the Short Physical Performance Battery (43.3% vs 26.6%, P-value < 0.01).Similarly, more women had cognitive impairment (83.2% vs 62.9%, P-value < 0.01) and reported falling (48.8% vs 34.0%, P-value < 0.01). Women (adjusted mean ratio, AMR 1.17, 95% CI 1.05-1.30, P-value < 0.01), older age (AMR 1.11, 95% CI 1.07-1.16, P-value < 0.01), no formal education (AMR 1.39, 95% CI 1.06-1.82, P-value = 0.01), underweight (AMR 1.49, 95% CI 1.26-1.76, P-value < 0.01), World Health Organization (WHO) stage 3 or 4 (AMR 1.11, 95% CI 0.01-1.22, P-value = 0.04) and having two or more NCDs (AMR 1.11, 95% CI 1.00-1.23, P-value = 0.04) were associated with a higher number of geriatric syndromes. The prevalence of geriatric syndromes was high among older PLHIV and was more common in women. There is a need to incorporate the screening and management of geriatric syndromes into the care of older PLHIV in sub-Saharan Africa, with a particular focus on women.

The dual burden of living with HIV and negotiating life stage changes has been identified as a contributing factor to lapsed adherence among adolescents with HIV in sub-Saharan Africa. While psychosocial support can promote medication adherence, most interventions in use with adolescents were originally developed for the general population creating a gap in appropriate support. Life-stage-appropriate, evidence-based psychosocial support interventions have been used with young people in high-income contexts, prompting interest in their use in low-income contexts. However, many interventions are less effective when implemented outside of their original settings, hence the need for modifications before implementation. We aimed to culturally adapt an evidence-based psychosocial support intervention designed to improve the mental health of young people for use among adolescents with HIV in a sub-Saharan African context and to explore the acceptability of the adapted intervention among adolescents. We engaged thirty stakeholders (n = 30) in Kampala, Uganda including psychologists, psychiatrists, social workers, HIV counselors, religious leaders and adolescent peers from December 2021 to April 2022 to modify an evidence-based intervention for adolescents. Key adaptations included simplifying the language, adding local practices, integrating locally relevant slang and stories into therapy, introducing racially-congruent visuals and cards representing emotions, and adjusting therapy materials for use in resource-constrained settings. We then tested the acceptability of the intervention in a small sample of service users using a qualitative approach. We recruited nine adolescents with HIV from a participating clinic in Kampala, delivered six 90-minute sessions of the adapted intervention across three weeks and conducted in-depth interviews to assess the acceptability of the intervention. We used thematic analysis to analyze the qualitative data. The adapted intervention was perceived as acceptable among adolescents with HIV, with many stating that it helped them overcome fears, increased their self-acceptance, and gave them the confidence to make careful health-enhancing decisions.