Advanced HIV Disease Research Articles

Regional and Racial Disparities in HIV-Related Kidney Disease.

Clinical Background and Epidemiology: Worldwide, an estimated 38 million people are living with HIV infection. The classic kidney disease of HIV infection, commonly known as HIV-associated nephropathy, is a collapsing form of focal segmental glomerulosclerosis that almost exclusively affects individuals of African descent with advanced HIV disease. People living with HIV are also at risk for immune-complex kidney diseases, antiretroviral nephrotoxicity, and kidney disease due to co-infections and comorbidities. Challenges: The burden of HIV-related kidney disease is greatest in traditionally disadvantaged populations in resource-limited settings in sub-Saharan Africa and the Caribbean and among minority populations in the United States and Europe. Factors contributing to these disparities include a higher prevalence of HIV infection, limited access to optimal antiretroviral therapy, and genetic susceptibility to kidney disease. Treatment and Prevention: Current treatment guidelines recommend the initiation of life-long antiretroviral therapy in all people living with HIV to prevent AIDS and non-AIDS complications, including kidney disease. People living with HIV who progress to end-stage kidney disease despite treatment are candidates for dialysis and kidney transplant, including the possibility of accepting organs from HIV-positive donors in some settings. Although HIV prevention is currently the only definitive solution, expanding access to antiretroviral therapy, dialysis, and kidney transplantation in people living with HIV are important intermediate steps to address the global burden of HIV-related kidney disease.

113. Advanced HIV Disease Among Adults in the African Cohort Study (AFRICOS)

BackgroundIn the “test and treat” era, early ART may decrease the prevalence of advanced HIV disease (AHD), defined as having a CD4 cell count < 200 cells/µL or World Health Organization (WHO) clinical stage III or IV disease. We assessed trends in AHD and ART coverage and describe factors associated with AHD among adults living with HIV (LWH) across four countries before and during the “test and treat” era.MethodsThe African Cohort Study (AFRICOS) is a prospective cohort enrolling adults at risk for HIV or LWH from 12 facilities in Uganda, Kenya, Tanzania and Nigeria. Clinical history review and laboratory testing were performed at enrollment and every 6 months. Serum cryptococcal antigen screening (CrAg) was performed in a subset with CD4 < 200 at enrollment. Logistic regression was used to estimate odds ratios for factors associated with CD4 < 200.ResultsFrom January 2013–December 2019, 2934 adults LWH were enrolled (median age 38 years [interquartile range, 31–46 years], 41.5% men). Of 2903 with CD4 results at enrollment, 567 (19.5%) had CD4 < 200. Despite consistent increases in ART coverage since 2016, across all countries the prevalence of AHD did not decline below levels observed in 2013 until 2019. The prevalence of CD4 < 200 did not significantly decline from 11.9% (range 9.1–25.0%) in 2013 to 10.3% (range 0–16%) in 2019, p=0.7, while ART coverage increased from 74.7% (range 68.3–93.8%) in 2013 to 97.5% (range 86–100%) in 2019, p= < 0.01 (Figure 1). Factors associated with a higher risk of CD4 < 200 at enrollment were being enrolled in Tanzania, male sex, age >29 years, having a primary or some secondary education or above, and WHO stage II disease or higher. Factors associated with a lower risk of CD4 < 200 were >1 year since HIV diagnosis and being on ART for at least 6 months (Table 1). Among those with CD4 < 200 at enrollment, the most commonly reported comorbidities included HIV wasting syndrome (9.3%) and tuberculosis (TB) (2.3%); 19 (3.4%) of 564 adults screened were CrAg positive.Figure 1: Trends in Percentage of Participants with CD4 <200 and ART coverage at Study Enrollment by Country and Year Table 1: Factors associated with CD4 <200 cells/mm3 at Study Enrollment ConclusionDespite the scale-up of ART in the era of “test and treat”, AHD prevalence has only recently trended downward. Continued efforts towards early HIV diagnosis and timely ART initiation are needed to reduce the risk for CD4< 200. Strategies to increase TB screening, prophylaxis, and treatment are essential to reduce morbidity.Disclosures All Authors: No reported disclosures

1008. Disease Severity Impact on Long-Term Virologic Response to Ibalizumab in Expanded Access Protocol (TMB-311)

BackgroundThe principal goal of antiretroviral therapy (ART) is durable suppression of HIV RNA. In treatment-experienced (TE) patients, ongoing viremia can lead to further accumulation of drug resistance, increased morbidity and mortality. ART efficacy often depends on HIV disease severity; therefore, we sought to assess its impact on long-term virologic suppression in patients treated with Ibalizumab (IBA), the first long-acting, post-attachment inhibitor approved for multi-drug resistant (MDR) HIV-1 treatment.MethodsIn TMB-301, a Phase 3 study, 40 TE patients with viral load (VL) >1000 copies/mL (c/mL) received an intravenous (IV) loading dose of IBA (2000mg) followed by maintenance doses (800mg IV) every 2 weeks combined with an optimized background regimen. Patients who completed TMB-301 in the US (n=27) continued to an expanded access protocol TMB-311. To determine the impact of baseline (BL) disease on long-term virologic response, we conducted an on-treatment analysis stratified by BL VL and CD4 count up to week 96. Differences in the proportion of suppressed (< 50 c/mL) individuals among the strata were assessed by Fisher’s exact test.ResultsMedian BL VL and CD4 count were 35,350 c/mL and 73 cells/mL, respectively. The number of patients in the VL strata were 11, 17 and 12 for VL < 10,000, 10,000-70,000, and >70,000 c/mL, respectively. There were 12, 10, 5 and 13 patients in the subgroups with CD4 count < 10, 10-100, >100-200 and >200 cells/µL. Population disease severity was reflected by four deaths (unrelated to study drug). Overall, the proportion of suppressed patients increased from 55% at week 24 (n=31) to 75% for patients remaining on treatment for 96 weeks (n=20). Median VL decrease was 2.9 log10 c/mL. Notably, no statistically significant differences were found across groups. Among patients with advanced HIV disease, 66.7% with CD4 count < 10 cells/mL and 71.4% with VL >70,000 c/mL at BL remained fully suppressed at week 96.ConclusionIn TE patients with advanced HIV disease, maximal viral suppression with IBA was observed regardless of BL CD4 or VL strata if patients remained on treatment. This demonstrates that TE patients across the spectrum of HIV disease, can achieve viral suppression by using drugs with a new mechanism of action.Disclosures Princy Kumar, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Jason Leider, MD, PhD, THERA (Speaker’s Bureau) Jihad Slim, MD, Abbvie (Speaker’s Bureau)Gilead (Speaker’s Bureau)Jansen (Speaker’s Bureau)Merck (Speaker’s Bureau)ViiV (Speaker’s Bureau) Graeme Moyle, MD, Theratechnologies (Consultant) Maurice Leonard, PhD, Theratechnologies Europe Ltd (Employee, Shareholder) R Brandon Cash, PharmD, Theratechnologies (Employee) Steven Weinheimer, PhD, TaiMed Biologics USA (Employee) Pedro Mesquita, PhD, Theratechnologies, Inc. (Employee)

Performance of Xpert® MTB/RIF and Determine™ TB-LAM Ag in HIV-infected adults in peri-urban sites in Zambia.

Peri-urban health facilities providing HIV and TB care in Zambia. To evaluate 1) the impact of Xpert® MTB/RIF on time-to-diagnosis, treatment initiation, and outcomes among adult people living with HIV (PLHIV) on antiretroviral therapy (ART); and 2) the diagnostic performance of Xpert and Determine™ TB-LAM Ag assays. Quasi-experimental study design with the first cohort evaluated per standard-of-care (SOC; first sputum tested using smear microscopy) and the second cohort per an algorithm using Xpert as initial test (intervention phase; IP). Xpert testing was provided onsite in Chongwe District, while samples were transported 5-10 km in Kafue District. TB was confirmed using mycobacterial culture. Among 1350 PLHIV enrolled, 156 (15.4%) had confirmed TB. Time from TB evaluation to diagnosis (P = 0.018), and from evaluation to treatment initiation (P = 0.03) was significantly shorter for IP than for SOC. There was no difference in all-cause mortality (7.0% vs. 8.6%). TB-LAM Ag showed higher sensitivity with lower CD4 cell count: 81.8% at CD4 < 50 cells/mm3 vs. 31.7% overall. Xpert improved time to diagnosis and treatment initiation, but there was no difference in all-cause mortality. High sensitivity of Determine TB-LAM Ag at lower CD4 count supports increased use in settings providing care to PLHIV, particularly with advanced HIV disease.

Diagnostic Accuracy of the Biosynex CryptoPS Cryptococcal Antigen Semiquantitative Lateral Flow Assay in Patients with Advanced HIV Disease.

High cryptococcal antigen (CrAg) titers in blood are associated with subclinical meningitis and mortality in CrAg-positive individuals with advanced HIV disease (AHD). We evaluated a novel semiquantitative lateral flow assay (LFA), CryptoPS, that may be able to identify individuals with high CrAg titers in a cohort of AHD patients undergoing CrAg screening. In a prospective cohort of patients with AHD (CD4 cell count, ≤200/μl) receiving CD4 count testing, whole blood was tested for CrAg by CryptoPS and the IMMY LFA; the two assays were conducted by two different operators, each blind to the results of the other assay. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CryptoPS were assessed against the IMMY LFA as a reference. CryptoPS low-titer (T1 band) and high-titer (T2 band) results were compared with IMMY LFA titers obtained through serial dilution. A total of 916 specimens were tested. The sensitivity of the CryptoPS assay was 61.0% (25/41) (95% confidence interval [95% CI], 44.5 to 75.8%), its specificity was 96.6% (845/875) (95% CI, 95.1 to 97.7%), its PPV was 45.5% (95% CI, 32.0 to 59.4%), and its NPV was 98.1% (95% CI, 97.0 to 98.9%). All (16/16) CryptoPS false-negative results were obtained for samples with IMMY titers of ≤1:160. Of 29 patients (30 specimens) who tested positive by CryptoPS but negative by the IMMY LFA, none developed cryptococcal meningitis over 3 months of follow-up without fluconazole. Median CrAg titers were 1:20 (interquartile range [IQR], 0 to 1:160) in CryptoPS T1-positive samples and 1:2,560 (IQR, 1:1,280 to 1:10,240) in T2-positive samples. We conclude that the diagnostic accuracy of the CryptoPS assay was suboptimal in the context of CrAg screening, with poor sensitivity at low CrAg titers. However, the CryptoPS assay reliably detected individuals with high titers, which are associated with poor outcomes.

Opportunistic fungal infections in persons living with advanced HIV disease in Lagos, Nigeria; a 12-year retrospective study.

Nigeria has a large estimated burden of AIDS-related mycoses. We aimed to determine the proportion of patients with AIDS-related opportunistic fungal infections (OFIs) at an urban antiretroviral treatment (ART) centre in Nigeria. A retrospective analysis of a cohort of ART-naïve, HIV-infected patients, assessed for ART eligibility and ARTexperience at the PEPFAR outpatient clinic at Lagos University Teaching Hospital over a 12-year period (April 2004-February 2016) was conducted. During this period, 7,034 patients visited the clinic: 4,797 (68.2%) were female; 6161 patients had a recorded baseline CD4 count, and the median CD4 count was 184 cells/µl (IQR, 84-328). A baseline HIV-1 viral load (VL) was recorded for 5,908 patients; the median VL was 51,194 RNA copies/ml (IQR, 2,316-283,508) and 6,179/7046(88%) had initiated ART. Some 2,456 (34.9%) had a documented opportunistic infections, of whom 1,306 (18.6%) had an opportunistic fungal infection. The total number of OFI episodes was 1,632: oral candidiasis (n=1,473, 90.3%), oesophageal candidiasis (n=118; 8%), superficial mycoses (n=23; 1.6%), Pneumocystis pneumonia (PJP) (n=13; 0.8%), and cryptococcal meningitis(CM) (n=5; 0.4%). 113 (1.6%) were known to have died in the cohort. Approximately 1 in 5 HIV-infected patients in this retrospective cohort, most of whom had initiated ART, were clinically diagnosed with an OFI. Improved access to simple accurate diagnostic tests for CM and PJP should be prioritised for this setting.

Advanced HIV disease during the 'Treat All' era in Botswana.

Advanced HIV disease during the 'Treat All' era in Botswana.

Mortality in Perinatally HIV-infected Adolescents After Transition to Adult Care in Spain.

After the introduction of combination antiretroviral treatment, (ART) mortality in HIV-infected patients has dramatically decreased. However, it is still high in patients at risk, as adolescents transitioning to adult care (AC) without virologic control. The aim of this study was to characterize mortality and comorbidities of perinatally infected HIV (PHIV) patients after transition to AC. A multicenter retrospective study from patients included in the CoRISpe-FARO Spanish cohort was conducted. PHIV patients who died after transition to AC between 2009 and 2019 were included. Clinical, immunovirologic characteristics, treatments received, comorbidities and causes of death were described. Among 401 PHIV patients, 14 died (3.5%). All were Spanish, 11/14 (78.6%) women. The median age at diagnosis was 1.5 years (interquartile range [IQR] 0.5-3.9), at transfer to AC was 18 years [16.1-19.9] and at death was 25.8 years [23.6-27.1]. In pediatric units [pediatric care (PC)], CD4+ nadir was 85 cells/μL [IQR 9.7-248.5] and 6/14 patients were classified as C-clinical stage. During AC, all patients were on C-clinical stage and CD4+ nadir dropped to 11.5 cells/μL [4.5-43.3]. cART adherence was extremely poor: in PC, 8/14 patients registered voluntary treatment interruptions; only one had undetectable VL at transition. In AC, 12/14 patients stopped treatment 2 or more periods of time. All deaths were related to advanced HIV disease. Mental health disorders were observed in 7/14 (50%). Main complications described: recurrent bacterial infections (57.1%), wasting syndrome (42.9%), esophageal candidiasis (28.6%) and Pneumocystis jirovecii pneumonia (28.6%). Four women had 11 pregnancies; 5 children were born (none infected). Young adults PHIV infected who transition to AC without virologic suppression or proven ability to adhere to ART are at high risk of mortality. Mortality was noted as a consequence of advanced HIV disease, frequent mental health problems and poor adherence to ART.

Prevalence of and factors associated with advanced HIV disease among newly diagnosed people living with HIV in Guangdong Province, China.

IntroductionA high proportion of people living with HIV (PLHIV) present for care with advanced HIV disease (AHD), which is detrimental to “90‐90‐90” targets to end AIDS by 2030. This study aimed to explore the prevalence of and factors related to AHD among newly diagnosed PLHIV in Guangdong Province, China.MethodsNewly diagnosed PLHIV were recruited from six cities in Guangdong Province from May 2018 to June 2019. AHD was defined as an initial CD4 count <200 cells/µL or an AIDS‐defining event within one month of HIV diagnosis. Data from a questionnaire and the national HIV surveillance system were used to explore the potential factors related AHD.ResultsA total of 400 of 997 newly diagnosed PLHIV were defined as having AHD with a proportion of 40.1%. After adjusting for statistically significant variables in univariate analysis, multivariable logistic regressions showed that individuals aged 30 to 39 years (adjusted odds ratio (aOR) = 1.77, 95% confidence interval (CI): 1.13 to 2.79) and ≥50 years (aOR = 1.98, 95% CI: 1.15 to 3.43) were at a higher risk of AHD than those aged 18 to 29 years. Participants diagnosed by voluntary counselling and testing (VCT) clinics were less likely to have AHD (aOR = 0.67, 95% CI: 0.48 to 0.94) than those diagnosed at medical facilities. Participants who had ever considered HIV testing (aOR = 0.66, 95% CI: 0.45 to 0.98) and who had high social support (aOR = 0.73, 95% CI: 0.55 to 0.97) were at a lower risk of AHD, whereas participants who had HIV‐related symptoms within one year before diagnosis were at a higher risk of AHD (aOR = 2.09, 95% CI: 1.58 to 2.77). The most frequent reason for active HIV testing was “feeling sick” (42.4%, 255/601), and the main reason for never considering HIV testing was “never thinking of getting HIV” (74.0%, 542/732).ConclusionsLow‐risk perception and a lack of awareness of HIV‐related symptoms resulted in a high proportion of AHD in Guangdong Province, especially among the elderly, those diagnosed at medical facilities and those with low social support. Strengthening AIDS education and training programmes to scale up HIV testing through provider‐initiated testing and counselling in medical facilities and VCT could facilitate early HIV diagnosis.

A Journey of Hope: giving research participants a voice to share theirexperiences and improve community engagement aroundadvanced HIV disease in Uganda.

Over the last decade excellent progress has been made globally in HIV management thanks to antiretroviral therapy (ART) rollout and international guidelines now recommending immediate initiation of ART in people living with HIV. Despite this, advanced HIV disease (CD4 less than 200 cells/mL) and opportunistic infections remain a persistent challenge and contribute significantly to HIV-associated mortality, which equates to 23,000 deaths in Uganda in 2018 alone. Our Meningitis Research Team based in Uganda is committed to conducting clinical trials to answer important questions regarding diagnostics and management of HIV-associated opportunistic infections, including tuberculosis and cryptococcal meningitis. However, clinical research is impossible without research participants and results are meaningless unless they are translated into benefits for those affected by the disease. Therefore, we held a series of community engagement events with the aims of 1) giving research participants a voice to share their experiences of clinical research and messages of hope around advanced HIV disease with the community, 2) dispelling myths and stigma around HIV, and 3) raising awareness about the complications of advanced HIV disease and local clinical research and recent scientific advances. The purpose of this Open Letter is to describe our community engagement experience in Uganda, where we aimed to give clinical research participants a greater voice to share their experiences.These activities build upon decades of work in HIV community engagement and lays a platform for future research and engagement activities.

Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: week 96 results of the phase 3 BRIGHTE study

Fostemsavir, a prodrug of the first-in-class attachment inhibitor, temsavir, is indicated for heavily treatment-experienced individuals with multidrug-resistant HIV-1. We previously reported superior efficacy of fostemsavir versus placebo in the randomised cohort of the BRIGHTE study after 8-day functional monotherapy (primary endpoint); here we report planned interim analyses through week 96. BRIGHTE (NCT02362503) is an ongoing multicentre, two-cohort, phase 3 trial, done at 108 centres in 22 countries. We enrolled heavily treatment-experienced adults (≥18 years) failing antiretroviral therapy (HIV-1 RNA ≥400 copies per mL) into two cohorts: the randomised cohort, in which patients with one or two fully active antiretrovirals remaining received oral fostemsavir (600 mg twice a day) or placebo in combination with their failing regimen for 8 days, followed by fostemsavir plus optimised background therapy; or the non-randomised cohort, in which patients with no remaining antiretroviral options received oral fostemsavir (600 mg twice a day) plus optimised background therapy from day 1. Endpoints for the week 96 interim analyses included the proportions of participants with plasma HIV-1 RNA of less than 40 copies per mL, changes from baseline in CD4 cell counts, and the frequency of adverse events, adverse events leading to discontinuation, and deaths. The intention-to-treat exposed population and the safety population both included all participants who received at least one dose of study treatment. The response rates (proportion of participants with HIV-1 RNA <40 copies per mL) in the intention-to-treat exposed population were calculated via snapshot analysis at weeks 24, 48, and 96. Between Feb 23, 2015, and Aug 11, 2016, 371 participants were enrolled and treated, of which 272 participants were in the randomised cohort and 99 in the non-randomised cohort. 320 (86%) of 371 reported a history of AIDS. In the randomised cohort, rates of virological suppression (HIV-1 RNA <40 copies per mL) increased from 53% (144 of 272) at week 24 to 60% (163 of 272) at week 96. Response rates in the non-randomised cohort were 37% (37 of 99) at week 24 and week 96. Mean increases in CD4 counts from baseline at week 96 were 205 cells per μL (SD 191) in the randomised cohort and 119 cells per μL (202) in the non-randomised cohort. Mean CD4/CD8 ratio increased from 0·20 at baseline to 0·44 at week 96 in the randomised cohort. Few adverse events led to discontinuation (26 [7%] of 371). 12 (4%) of 272 people in the randomised cohort and 17 (17%) of 99 in the non-randomised cohort died; the median baseline CD4 count for participants who died was 11 cells per μL. In heavily treatment-experienced individuals with advanced HIV-1 disease and limited treatment options, fostemsavir-based antiretroviral regimens were generally well tolerated and showed a distinctive trend of increasing virological and immunological response rates through 96 weeks; these findings support fostemsavir as a treatment option for this vulnerable population. ViiV Healthcare.

EP26 HIV infection masquerading as connective tissue disease

Case report - IntroductionConnective tissue diseases are multisystem disorders. Diagnosis and evaluation of suspected cases is not straight forward in most of the cases. This case describes the significance of considering a broader approach when evaluating a suspected case of connective tissue disease.Case report - Case descriptionWe describe a case of 58 years old non-smoker lady, presented with acute onset livedo reticularis rash on lower limbs and background of sicca symptoms, oral ulcers, fatigue, paraesthesias in feet and arthralgias without any systemic or inflammatory joint symptoms.General examination showed livedo reticularis rash on both elbows and lower legs. There was no evidence of peripheral joint synovitis, but she had nodal osteoarthritis in her hands. Systemic examination was unremarkable.Investigations revealed anaemia, pancytopenia, ESR of 77, low C4 and urine dipstick positive for leucocytes, nitrates, protein, and blood. Schirmer’s test, ANA and ENA screen was positive with positive RNP and SMdp antibody. She also had hypergammaglobulinemia in a polyclonal pattern. Nerve Conduction and EMG studies revealed mild axonal sensory neuropathy.Case report - DiscussionThis lady appeared to have mixed connective tissue disease with mixed features of Sjögren’s syndrome and systemic lupus erythematosus. She was started on Hydroxychloroquine but stopped it shortly after developing floaters in her eye. She had poor response to Depomedrone injection. She had ongoing symptoms of fatigue, weight-loss, loose stools, and abdominal pain, investigated further and CT scan showed hyperdense liver lesions and mesenteric lymphadenopathy. Esophagogastroduodenoscopy showed oesophageal candidiasis. She was admitted with progressive symptoms. Further investigations showed a positive HIV test and liver biopsy came back positive for anaplastic lymphoma, later she was diagnosed with advanced HIV disease, rapidly deteriorated with neutropenic sepsis and multi-organ failure, and unfortunately died.Case report - Key learning pointsThis lady initially presented with symptoms of connective tissue disease and investigations in keeping with this diagnosis. Unfortunately, by the time she was tested for HIV infection, it was already too late. There could be overlap of symptoms of connective tissue disease and viral infections e.g. HIV infection. Autoantibodies may be falsely positive in infections e.g. HIV and in malignancy. Risk factors of HIV infection should be considered during assessment of multisystem diseases like connective tissue diseases particularly prior to immunosuppression. Viral screening including HIV test should be considered in all high-risk patients and particularly if the symptoms are atypical and do not quite fit well with the diagnosis.

Pulmonary tuberculosis masquerading as coronavirus disease 2019 in an HIV-infected individual with advanced immune suppression

Pulmonary tuberculosis masquerading as coronavirus disease 2019 in an HIV-infected individual with advanced immune suppression

Causes of fever in Tanzanian adults attending outpatient clinics: a prospective cohort study

ObjectivesExploring fever aetiologies improves patient management. Most febrile adults are outpatients, but all previous studies were conducted in inpatients. This study describes the spectrum of diseases in adults attending outpatient clinics in urban Tanzania. MethodsWe recruited consecutive adults with temperature ≥38°C in a prospective cohort study. We collected medical history and performed a clinical examination. We performed 27 364 microbiological diagnostic tests (rapid tests, serologies, cultures and molecular analyses) for a large range of pathogens on blood and nasopharyngeal samples. We based our diagnosis on predefined clinical and microbiological criteria. ResultsOf 519 individuals, 469 (89%) had a clinically or microbiologically documented infection and 128 (25%) were human immunodeficiency virus (HIV) -infected. We identified 643 diagnoses: 264 (41%) acute respiratory infections (36 (5.6%) pneumonia, 39 (6.1%) tuberculosis), 71 (11%) infections with another focus (31 (4.8%) gastrointestinal, 26 (4.0%) urogenital, 8 (1.2%) central nervous system) and 252 (39%) infections without focus (134 (21%) dengue, 30 (4.7%) malaria, 28 (4.4%) typhoid). Of the 519 individuals, 318 (61%), 179 (34%), 30 (6%) and 15 (3%), respectively, had a viral, bacterial, parasitic and fungal acute infection. HIV-infected individuals had more bacterial infections than HIV-negative (80/122 (66%) versus 100/391 (26%); p < 0.001). Patients with advanced HIV disease had a higher proportion of bacterial infections (55/76 (72%) if CD4 ≤200 cells/mm3 and 25/52 (48%) if CD4 >200 cells/mm3, p 0.02). ConclusionsViral diseases caused most febrile episodes in adults attending outpatient clinics except in HIV-infected patients. HIV status and a low CD4 level strongly determined the need for antibiotics. Systematic HIV screening is essential to appropriately manage febrile patients.

Prevalence and incidence rate of tuberculosis among HIV-infected patients enrolled in HIV care, treatment, and support program in mainland Tanzania

BackgroundDespite improvements in access to antiretroviral therapy (ART), mortality in people living with human immunodeficiency virus (PLHIV) is still high and primarily attributed to tuberculosis (TB) infection. In Sub-Saharan Africa, approximately 80% of HIV-related mortality cases are associated with TB. Relatively little is known about the incidence of TB among PLHIV in Tanzania and the determinant factors. We report the prevalence and incidence rate of confirmed TB and determine association with selected demographic and program-related factors based on data in the national HIV care and treatment program from 2011 to 2014.MethodsWe used the Tanzania National AIDS Control Programme database to obtain information on all HIV clients enrolled in the HIV care and treatment program between January 2011 and December 2014. We analyzed retrospective cohort data to assess the prevalence and TB incidence rate per 1000 person-years. A multivariable Cox proportional hazards regression model was used to estimate hazard ratios and 95% confidence intervals for putatively associated factors.ResultsOver 4 years, there were 22,071 confirmed cases of pulmonary TB in 1,323,600 person-years. The overall TB incidence was around 16.7 (95% CI 16.4–16.9) cases per 1000 person-years. The annual incidence rate decreased by 12.4 % from 17.0 (95% CI 16.5–17.4) in 2011 to 14.9 (95% CI 14.5–15.4) in 2014. The TB incidence rate was higher in persons not using ART and in males than in females. The incidence of TB was higher in patients with advanced HIV disease and decreased with increasing age. The overall prevalence of TB was 2.2%, with a peak prevalence of 2.5% in 2013 and was higher among children < 15 years (3.2%) in the same year.ConclusionThe study found an overall decrease in the incidence of TB in PLHIV. Our results emphasize the need for early initiation of ART and the provision of TB preventive therapy for those PLHIV without active TB after intensified TB case-finding.

Utility of CD4 count measurement in the era of universal antiretroviral therapy: an analysis of routine laboratory data in Botswana.

National guidelines in Botswana recommend baseline CD4 count measurement and both CD4 and HIV viral load (VL) monitoring post-antiretroviral therapy (ART) initiation. We evaluated the utility of CD4 count measurement in Botswana in the era of universal ART. CD4 and VL data were analysed for HIV-infected adults undergoing CD4 count measurement in 2015-2017 at the Botswana Harvard HIV-Reference Laboratory. We determined (1) the proportion of individuals with advanced HIV disease (CD4 count<200 cells/µL) at initial CD4 assessment, (2) the proportion with an initial CD4 count ≥200 cells/µL experiencing a subsequent decline in CD4 count to <200 cells/µL, and (3) the proportion of these immunologically failing individuals who had virological failure. Logistic regression modelling examined factors associated with advanced HIV disease. CD4 count trajectories were assessed using locally weighted scatterplot smoothing (LOWESS) regression. Twenty-five per cent (3571/14423) of individuals with an initial CD4 assessment during the study period had advanced HIV disease at baseline. Older age [≥ 35years; adjusted odds ratio (aOR) 1.9; 95% confidence interval (CI) 1.8-2.1] and male sex were associated with advanced HIV disease. Fifty per cent (7163/14423) of individuals had at least two CD4 counts during the study period. Of those with an initial CD4 count ≥200 cells/µL, 4% (180/5061) experienced a decline in CD4 count to <200 cells/µL; the majority of CD4 count declines were in virologically suppressed individuals and transient. One-quarter of HIV-positive individuals in Botswana still present with advanced HIV disease, highlighting the importance of baseline CD4 count measurement to identify this at-risk population. Few with a baseline CD4 count ≥200 cells/µL experienced a drop below 200 cells/µL, suggesting limited utility for ongoing CD4 monitoring.

Assessing late presentation for female adolescents and young women with HIV in 2019, South Africa

Abstract Background South Africa has the biggest HIV epidemic in the world, with an estimated 7.1million people living with HIV in 2018. In 2016, women aged 15-24 contributed 37% of new infections. Poverty, low status, gender-based violence (GBV) and intergenerational relationships possibly contribute to this disparate HIV prevalence. The objective of this study was to describe very advanced HIV disease (CD4&amp;lt; count &amp;lt;100cells/µL) amongst 15-24 year old females by interrogating routine laboratory CD4 data. Methods Specimen level CD4 laboratory data of female patients aged 15-24 was extracted for the 2019 calendar year. Patients were categorized as adolescents (15-19) or young women (20-24), in age categories of (i) 15-16, (ii) 17-19, (iii) 20-21 and (iv) 22-24 years. Frequency tables were used to report test volumes and the percentage of samples with counts &amp;lt;100 cells/µl. Results Amongst 259 088 CD4 outcomes extracted, 5.4% of samples had counts &amp;lt;100 cells/µl, with 75.4% of samples from young women and 24.6% from adolescents. Most samples reported an age between 22-24 (52.2%), with the lowest proportion (5.8%) noted in 15-16 year olds. Median CD4 was 485 cells/µL, with medians of 490 and 470 cells/µl noted for young women and adolescents respectively. Review of the &amp;lt;100 cells/µl group revealed a median of 43 cells/µL, with 38 and 46 cells/µL reported for young women and adolescents respectively. There was no significant association between the median CD4 and age category. Very advanced HIV disease by age categories of 15-16, 17-19, 20-21 and 22-24, comprised 7.0%, 5.6%, 5.0% and 5.3% respectively. Conclusions This study demonstrated unacceptable rates of very advanced HIV disease in female adolescents and young women, suggesting HIV seroconversion as teenagers or younger. Evidence-based specific health care interventions for these girls are urgently required, including tailoring social services and health facilities to secure the sexual health of girls and young women. Key messages Very advanced HIV disease presentation in female adolescents is unacceptably high. Young women and adolescents with late presentation.

Myocardial Inflammatory Changes Before and After Antiretroviral Therapy Initiation in People With Advanced Human Immunodeficiency Virus Disease.

Because of the high frequency of late presentation of human immunodeficiency virus (HIV) disease in our population, we decided to explore the presence of myocarditis among people with HIV infection and advanced immunosuppression (less than 200 CD4+ cells/μL) and to describe the inflammatory changes observed after combined antiretroviral therapy initiation in an observational, longitudinal, prospective cohort. We performed both cardiovascular magnetic resonance imaging and doppler transthoracic echocardiogram.

A Journey of Hope: giving research participants a voice to share their experiences and improve community engagement around advanced HIV disease in Uganda

Over the last decade excellent progress has been made globally in HIV management thanks to antiretroviral therapy (ART) rollout and international guidelines now recommending immediate initiation of ART in all HIV-positive people. Despite this, advanced HIV disease (CD4 less than 200 cells/mL) and opportunistic infections remain a persistent challenge and contribute significantly to HIV-associated mortality, which equates to 23,000 deaths in Uganda in 2018 alone. Our Meningitis Research Team based in Uganda is committed to conducting clinical trials to answer important questions regarding diagnostics and management of HIV-associated opportunistic infections, including tuberculosis and cryptococcal meningitis. However, clinical research is impossible without research participants and results are meaningless unless they are translated into benefits for those affected by the disease. Therefore, we held a series of community engagement events with the aims of giving clinical research participants a voice in sharing their experiences of clinical research and messages of hope around advanced HIV disease with the community, dispelling myths and stigma around HIV, raising awareness about the complications of advanced HIV disease and local ongoing clinical research and recent scientific advances. The purpose of this Open Letter is to describe our community engagement experience in Uganda, which we hope will lay the foundation for further clinical research public engagement activities, giving research participants a greater voice to share their experiences.

Advanced HIV disease in the Botswana combination prevention project: prevalence, risk factors, and outcomes.

To determine the proportion of individuals linking to HIV-care with advanced HIV-disease (CD4 cell counts ≤200 cells/μl) in the Botswana Combination Prevention Project, describe the characteristics of these individuals, and examine treatment outcomes. A subanalysis of a cluster-randomized HIV-prevention trial. HIV status was assessed in 16-64-year-olds through home and mobile testing. All HIV-positive persons not on antiretroviral therapy were referred to local Ministry of Health and Wellness clinics for treatment. Analysis was restricted to the 15 intervention clusters. The proportion of individuals with advanced HIV disease was determined; associations between advanced HIV disease and sex and age explored; and rates of viral suppression determined at 1-year. Mortality and retention in care were compared between CD4 strata (CD4 cell counts ≤200 vs. >200 cells/μl). Overall, 17.2% [430/2499; 95% confidence interval (CI) 15.7-18.8%] of study participants had advanced HIV disease (CD4 cell counts ≤200 cells/μl) at time of clinic linkage. Men were significantly more likely to present with CD4 cell counts 200 cells/μl or less than women [23.7 vs. 13.4%, adjusted odds ratio 1.9, 95% CI 1.5-2.3]. The risk of advanced HIV disease increased with increasing age (adjusted odds ratio 2.2, 95% CI 1.4-3.2 >35 vs. <25 years). Patients with CD4 cell counts 200 cells/μl or less had significantly higher rates of attrition from care during follow-up (hazards ratio 1.47, 95% CI 1.1-2.1). Advanced HIV disease due to late presentation to or disengagement from antiretroviral therapy care remains common in the Treat All era in Botswana, calling for innovative testing, linkage, and treatment strategies to engage and retain harder-to-reach populations in care.