Browsing by Subject "Viral load"
Now showing 1 - 10 of 13
Results Per Page
Sort Options
Item 1270. HIV Drug Resistance and Viral Outcomes after 2nd-line Antiretroviral Failure in Kenya(Oxford University Press, 2022) Ali, Shamim M.; Humphrey, John; Novitsky, Vladimir; Sang, Edwin; DeLong, Allison; Jawed, Bilal; Kemboi, Emmanuel; Goodrich, Suzanne; Gardner, Adrian; Hogan, Joseph W.; Kantor, Rami; Medicine, School of MedicineBackground: Program data on HIV drug resistance and clinical outcomes after 2nd-line antiretroviral therapy (ART) failure in resource-limited settings are limited, yet can inform care, particularly with better ART access and options. Methods: We examined resistance upon 2nd-line failure and subsequent viral outcomes at the Academic Model Providing Access to Healthcare (AMPATH) in Kenya. Charts of people with genotypes upon 2nd-line failure up to 6/2021 were reviewed; and associations with viral suppression (< 1000 copies/mL) closest to 12 months post-genotyping were determined using bi- and multivariate analyses, adjusting for age, sex, time on ART, switch to 3rd-line (darunavir-, dolutegravir-, and/or raltegravir-based ART), and any resistance to regimens upon viral load (VL) testing. Results: Of 194 participants (53% female; median age 41 years; median 3.3 and 4.1 years on 1st- and 2nd-line), 60% were on lopinavir/ritonavir and 40% on atazanavir/ritonavir-based regimens. Overall, 178 (92%) had any resistance: 19% mono-, 40% dual-, 41% triple-class; 79% to NRTIs; 81% NNRTIs; and 43% PIs - 33% of those on lopinavir/ritonavir; 58% on atazanavir/ritonavir (p< 0.001); 24% with intermediate-high predicted resistance to darunavir/ritonavir (12 upon LPV/ritonavir, and 8 upon atazanavir/ritonavir failure; p=0.98). Of 140/194 people with post-genotype VLs, 55% stayed on 2nd-line, and 45% switched to 3rd-line. Of those 140, 72% virally suppressed (89% who switched to 3rd-line; 58% who didn't), and 75% had any resistance to their regimen at post-genotype VL (90% who switched to 3rd-line; 62% who didn't). In bivariate analysis, suppression was associated with switching to 3rd-line, and with resistance upon VL testing (Table). In multivariate analysis, suppression remained more likely among those who switched to 3rd-line, and association with resistance was less pronounced. Conclusion: In a large Kenyan HIV program, high resistance upon 2nd-line failure, high failure rates, and suppression association with 3rd-line switch suggest the need for dedicated management of this vulnerable population. Potential association between resistance and better viral outcomes, similar to reports upon 1st-line failure, needs further data and suggests significance of inadequate adherence.Item Achieving consistency in measures of HIV-1 viral suppression across countries: derivation of an adjustment based on international antiretroviral treatment cohort data(Wiley, 2021) Johnson, Leigh F.; Kariminia, Azar; Trickey, Adam; Yiannoutsos, Constantin T.; Ekouevi, Didier K.; Minga, Albert K.; Pascom, Ana Roberta Pati; Han, Win Min; Zhang, Lei; Althoff, Keri N.; Rebeiro, Peter F.; Murenzi, Gad; Ross, Jonathan; Hsiao, Nei-Yuan; Marsh, Kimberly; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthIntroduction: The third of the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets is to achieve a 90% rate of viral suppression (HIV viral load <1000 HIV-1 RNA copies/ml) in patients on antiretroviral treatment (ART) by 2020. However, some countries use different thresholds when reporting viral suppression, and there is thus a need for an adjustment to standardize estimates to the <1000 threshold. We aim to propose such an adjustment, to support consistent monitoring of progress towards the "third 90" target. Methods: We considered three possible distributions for viral loads in ART patients: Weibull, Pareto and reverse Weibull (imposing an upper limit but no lower limit on the log scale). The models were fitted to data on viral load distributions in ART patients in the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration (representing seven global regions) and the ART Cohort Collaboration (representing Europe), using separate random effects models for adults and children. The models were validated using data from the World Health Organization (WHO) HIV drug resistance report and the Brazilian national ART programme. Results: Models were calibrated using 921,157 adult and 37,431 paediatric viral load measurements, over 2010-2019. The Pareto and reverse Weibull models provided the best fits to the data, but for all models, the "shape" parameters for the viral load distributions differed significantly between regions. The Weibull model performed best in the validation against the WHO drug resistance survey data, while the Pareto model produced uncertainty ranges that were too narrow, relative to the validation data. Based on these analyses, we recommend using the reverse Weibull model. For example, if a country reports an 80% rate of viral suppression at <200 copies/ml, this model estimates the proportion virally suppressed at <1000 copies/ml is 88.3% (0.800.56 ), with uncertainty range 85.5-90.6% (0.800.70 -0.800.44 ). Conclusions: Estimates of viral suppression can change substantially depending on the threshold used in defining viral suppression. It is, therefore, important that viral suppression rates are standardized to the same threshold for the purpose of assessing progress towards UNAIDS targets. We have proposed a simple adjustment that allows this, and this has been incorporated into UNAIDS modelling software.Item Blood and genital fluid viral load trajectories among treated and untreated persons with acute HIV infection in Malawi(Wolters Kluwer, 2022) Chen, Jane S.; Pettifor, Audrey E.; Nelson, Julie A. E.; Phiri, Sam; Pasquale, Dana K.; Kumwenda, Wiza; Kamanga, Gift; Cottrell, Mackenzie L.; Sykes, Craig; Kashuba, Angela D. M.; Tegha, Gerald; Krysiak, Robert; Thengolose, Isaac; Cohen, Myron S.; Hoffman, Irving F.; Miller, William C.; Rutstein, Sarah E.; Community and Global Health, Richard M. Fairbanks School of Public HealthBackground: Persons with acute HIV infection (AHI) are highly infectious and responsible for a disproportionate share of incident infections. Immediate antiretroviral therapy (ART) rapidly reduces blood viral loads (VLs), but genital VLs after ART initiation during AHI are less well described. Setting: Lilongwe, Malawi, 2012-2014. Methods: HIV-seronegative and HIV-serodiscordant persons aged ≥18 years were screened for AHI (RNA positive) and randomized to standard of care, behavioral intervention, or behavioral intervention plus short-term ART (raltegravir/emtricitabine/tenofovir) (1:2:2). Persons who were ART eligible under Malawi guidelines could receive first-line therapy. Blood and genital VLs were assessed at weeks 1, 4, 8, and 12. Fisher's Exact test was used to compare viral suppression by ART status. Results: Overall, 46 persons with AHI were enrolled; of whom, 17 started ART within 12 weeks. Median blood VL at AHI diagnosis was 836,115 copies/mL. At week 12, 7% (1/14) of those who initiated ART had a blood VL of ≥400 copies/mL, compared with 100% (23/23; P < 0.0001) of those who did not initiate ART (median VL: 61,605 copies/mL). Median genital VL at week 1 was 772 copies/mL, with 13 of 22 (59%) having VL of ≥400 copies/mL. At week 12, 0 of 10 (0%) of those who initiated ART had genital VL of ≥400 copies/mL, compared with 7 of 15 (47%) of those who did not initiate ART (P = 0.02). Conclusion: Although highly correlated, VLs in blood and genital fluids occupy discrete biological compartments with distinct virologic dynamics. Our results corroborate the dramatic reduction in both compartments after ART initiation. Increasing AHI screening and rapidly initiating treatment is key to interrupting transmission.Item Global estimates of viral suppression in children and adolescents and adults on antiretroviral therapy adjusted for missing viral load measurements: a multiregional, retrospective cohort study in 31 countries(Elsevier, 2021) Han, Win Min; Law, Matthew G.; Egger, Matthias; Wools-Kaloustian, Kara; Moore, Richard; McGowan, Catherine; Kumarasamy, Nagalingesawaran; Desmonde, Sophie; Edmonds, Andrew; Davies, Mary-Ann; Yiannoutsos, Constantin; Althoff, Keri N.; Cortes, Claudia P.; Mohamed, Thahira Jamal; Jaquet, Antoine; Anastos, Kathryn; Euvrard, Jonathan; Castelnuovo, Barbara; Salters, Kate; Esteves Coelho, Lara; Ekouevi, Didier K.; Eley, Brian; Diero, Lameck; Zaniewski, Elizabeth; Ford, Nathan; Sohn, Annette H.; Kariminia, Azar; IeDEA collaboration; Medicine, School of MedicineBackground: As countries move towards the UNAIDS's 95-95-95 targets and with strong evidence that undetectable equals untransmittable, it is increasingly important to assess whether those with HIV who are receiving antiretroviral therapy (ART) achieve viral suppression. We estimated the proportions of children and adolescents and adults with viral suppression at 1, 2, and 3 years after initiating ART. Methods: In this retrospective cohort study, seven regional cohorts from the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium contributed data from individuals initiating ART between Jan 1, 2010, and Dec 31, 2019, at 148 sites in 31 countries with annual viral load monitoring. Only people with HIV who started ART after the time a site started routine viral load monitoring were included. Data up to March 31, 2020, were analysed. We estimated the proportions of children and adolescents (aged <18 years at ART initiation) and adults (aged ≥18 years at ART initiation) with viral suppression (viral load <1000 copies per mL) at 1, 2, and 3 years after ART initiation using an intention-to-treat approach and an adjusted approach that accounted for missing viral load measurements. Findings: 21 594 children and adolescents (11 812 [55%] female, 9782 [45%] male) from 106 sites in 22 countries and 255 662 adults (163 831 [64%] female, 91 831 [36%] male) from 143 sites in 30 countries were included. Using the intention-to-treat approach, the proportion of children and adolescents with viral suppression was 7303 (36%) of 20 478 at 1 year, 5709 (30%) of 19 135 at 2 years, and 4287 (24%) of 17 589 at 3 years after ART initiation; the proportion of adults with viral suppression was 106 541 (44%) of 240 600 at 1 year, 79 141 (36%) of 220 925 at 2 years, and 57 970 (29%) of 201 124 at 3 years after ART initiation. After adjusting for missing viral load measurements among those who transferred, were lost to follow-up, or who were in follow-up without viral load testing, the proportion of children and adolescents with viral suppression was 12 048 (64% [plausible range 43-81]) of 18 835 at 1 year, 10 796 (62% [41-77]) of 17 553 at 2 years, and 9177 (59% [38-91]) of 15 667 at 3 years after ART initiation; the proportion of adults with viral suppression was 176 964 (79% [53-80]) of 225 418 at 1 year, 145 552 (72% [48-79]) of 201 238 at 2 years, and 115 260 (65% [43-69]) of 178 458 at 3 years after ART initiation. Interpretation: Although adults with HIV are approaching the global target of 95% viral suppression, progress among children and adolescents is much slower. Substantial efforts are still needed to reach the viral suppression target for children and adolescents.Item HIV infection drives IgM and IgG3 subclass bias in Plasmodium falciparum-specific and total immunoglobulin concentration in Western Kenya(BioMed Central, 2019-08-30) Odhiambo, Eliud O.; Datta, Dibyadyuti; Guyah, Bernard; Ayodo, George; Ondigo, Bartholomew N.; Abong’o, Benard O.; John, Chandy C.; Frosch, Anne E. P.; Pediatrics, School of MedicineBACKGROUND: HIV infection is associated with more frequent and severe episodes of malaria and may be the result of altered malaria-specific B cell responses. However, it is poorly understood how HIV and the associated lymphopenia and immune activation affect malaria-specific antibody responses. METHODS: HIV infected and uninfected adults were recruited from Bondo subcounty hospital in Western Kenya at the time of HIV testing (antiretroviral and co-trimoxazole prophylaxis naïve). Total and Plasmodium falciparum apical membrane antigen-1 (AMA1) and glutamate rich protein-R0 (GLURP-R0) specific IgM, IgG and IgG subclass concentrations was measured in 129 and 52 of recruited HIV-infected and uninfected individuals, respectively. In addition, HIV-1 viral load (VL), CD4+ T cell count, and C-reactive protein (CRP) concentration was quantified in study participants. Antibody levels were compared based on HIV status and the associations of antibody concentration with HIV-1 VL, CD4+ count, and CRP levels was measured using Spearman correlation testing. RESULTS: Among study participants, concentrations of IgM, IgG1 and IgG3 antibodies to AMA1 and GLURP-R0 were higher in HIV infected individuals compared to uninfected individuals (all p < 0.001). The IgG3 to IgG1 ratio to both AMA1 and GLURP-R0 was also significantly higher in HIV-infected individuals (p = 0.02). In HIV-infected participants, HIV-1 VL and CRP were weakly correlated with AMA1 and GLURP-R0 specific IgM and IgG1 concentrations and total (not antigen specific) IgM, IgG, IgG1, and IgG3 concentrations (all p < 0.05), suggesting that these changes are related in part to viral load and inflammation. CONCLUSIONS: Overall, HIV infection leads to a total and malaria antigen-specific immunoglobulin production bias towards higher levels of IgM, IgG1, and IgG3, and HIV-1 viraemia and systemic inflammation are weakly correlated with these changes. Further assessments of antibody affinity and function and correlation with risk of clinical malaria, will help to better define the effects of HIV infection on clinical and biological immunity to malaria.Item HIV viral load levels and CD4+ cell counts of youth in 14 cities(Wolters Kluwer, 2014) Ellen, Jonathan M.; Kapogiannis, Bill; Fortenberry, J. Dennis; Xu, Jiahong; Willard, Nancy; Duval, Anna; Pace, Jill; Loeb, Jackie; Monte, Dina; Bethel, James; Adolescent Medicine Trials Network for HIV/AIDS Interventions; Pediatrics, School of MedicineObjectives: To describe the HIV viral load and CD4 cell counts of youth (12-24 years) in 14 cities from March 2010 through November 2011. Methods: Baseline HIV viral load and CD4 cell count data were electronically abstracted in a central location and in an anonymous manner through a random computer-generated coding system without any ability to link codes to individual cases. Results: Among 1409 HIV reported cases, 852 participants had data on both viral load and CD4 cell counts. Of these youth, 34% had CD4 cell counts of 350 or less, 27% had cell counts from 351 to 500, and 39% had CD4 cell counts greater than 500. Youth whose transmission risk was male-to-male sexual contact had higher viral loads compared with youth whose transmission risk was perinatal or heterosexual contact. Greater than 30% of those who reported male-to-male sexual contact had viral loads greater than 50 000 copies, whereas less than 20% of heterosexual contact youth had viral loads greater than 50 000 copies. There were no differences noted in viral load by type of testing site. Conclusion: Most HIV-infected youth have CD4 cell counts and viral load levels associated with high rates of sexual transmission. Untreated, these youth may directly contribute to high rates of ongoing transmission. It is essential that any public health test and treat strategy place a strong emphasis on youth, particularly young MSM.Item Initial viral cycle threshold values in patients with COVID-19 and their clinical significance(BMC, 2022-06-28) AlBahrani, Salma; Alghamdi, Mohammed; Zakary, Nawaf; Jebakumar, Arulanantham Zechariah; AlZahrani, Samirah Jamaan; ElGezery, Mohamed Hany; Abdallah, Khaled Omar; Al‑Tawfiq, Jaffar A.; Medicine, School of MedicineBackground: The connection between initial viral cycle threshold (Ct) values of the SARS-CoV-2 with symptoms and hospital course is not clearly studied. Methods: This is a retrospective study of hospitalized COVID-19 patients from Jun 1st 2020 to March 30th, 2021 examining the relationship between initial viral cycle threshold (Ct) values of SARS-CoV-2 as obtained from nasopharyngeal samples. The clinical presentations and outcomes were analyzed in relation to the initial Ct values. Results: The study included 202 hospitalized COVID-19 patients with a mean age (± SD) of 54.75 (± 15.93) and 123 (60.9%) males and 79 (39.1%) females. Of all the patients, the most frequent comorbidity was diabetes mellitus (95; 47%) and the most frequent symptoms were fever (148; 73.3%) and cough (141; 69.8%). There was no significant difference in relation to underlying conditions, clinical presentation, radiographic and laboratory data among those with low, medium and high Ct values. The mean Ct values showed no statistical change over the 10-month study period. Conclusions: Initial SARS-CoV-2 Ct values did not show any association with clinical symptoms and did not predict the need for mechanical intubation or death.Item Outcomes After Second-Line Antiretroviral Therapy in Children Living with HIV in Latin America(Wolters Kluwer, 2021) Somerville, Kayla; Jenkins, Cathy A.; Carlucci, James G.; Person, Anna K.; Machado, Daisy Maria; Luque, Marco T.; Pinto, Jorge A.; Rouzier, Vanessa; Khalili Friedman, Ruth; McGowan, Catherine C.; Shepherd, Bryan E.; Rebeiro, Peter F.; Pediatrics, School of MedicineBackground: Little is known about the long-term outcomes of children living with HIV in Latin America. Few studies have examined antiretroviral therapy (ART) regimen switches in the years after the introduction of ART in this population. This study aimed to assess clinical outcomes among children who started second-line ART in the Caribbean, Central and South America network for HIV epidemiology. Methods: Children (<18 years old) with HIV who switched to second-line ART at sites within Caribbean, Central and South America network for HIV epidemiology were included. The cumulative incidence and relative hazards of virologic failure while on second-line ART, loss to follow-up, additional major ART regimen changes, and all-cause mortality were evaluated using competing risks methods and Cox models. Results: A total of 672 children starting second-line ART were included. Three years after starting second-line ART, the cumulative incidence of death was 0.10 [95% confidence interval (CI) 0.08 to 0.13], loss to follow-up was 0.14 (95% CI: 0.11 to 0.17), and major regimen change was 0.19 (95% CI: 0.15 to 0.22). Of those changing regimens, 35% were due to failure and 11% due to toxicities/side effects. Among the 312 children with viral load data, the cumulative incidence of virologic failure at 3 years was 0.62 (95% CI: 0.56 to 0.68); time to virologic failure and regimen change were uncorrelated (rank correlation -0.001; 95% CI -0.18 to 0.17). Conclusions: Poor outcomes after starting second-line ART in Latin America were common. The high incidence of virologic failure and its poor correlation with changing regimens was particularly worrisome. Additional efforts are needed to ensure children receive optimal ART regimens.Item Outcomes of retained and disengaged pregnant women living with HIV in Uganda(Public Library of Science, 2021-05-21) Kiragga, Agnes N.; Twinomuhwezi, Ellon; Banturaki, Grace; Achieng, Marion; Nampala, Juliet; Bagaya, Irene; Kigozi, Joanita; Castelnuovo, Barbara; Musick, Beverly S.; Hazra, Rohan; Yiannoutsos, Constantin T.; Wools-Kaloustian, Kara K.; Medicine, School of MedicineIntroduction: Loss-to-follow-up among women living with HIV (WLWHIV) may lead to unfavorable outcomes for both mother and exposed infant. This study traced WLWHIV disengaged from care and their infants and compared their outcomes with those retained in care. Methods: The study included WLWHIV who initiated ART during pregnancy at six public clinics in Uganda. A woman was defined as disengaged (DW) if she had not attended her 6-week post-partum visit by 10 weeks after her estimated date of delivery. DW were matched with retained women (RW) by age and duration on ART. Nurse counselors traced all selected DW via telephone and community visits to assess vital status, infant HIV sero-status and maternal HIV viral load through blood draws. Results: Between July 2017 and July 2018, 734 women (359 DW and 375 RW) were identified for the study. Tracing was attempted on 349 DW and 160 (44.6%) were successfully located and enrolled in the study. They were matched with 162 RW. Among DW, 52 (32.5%) transferred to another health facility. Very few DW, 39.0% were HIV virally suppressed (<1000 copies/ml) compared to RW 89.5%, P<0.001). Among 138 babies born to DW, 4.3% tested positive for HIV compared to 1.4% among babies born to RW (P = 0.163). Conclusion: Pregnant and breastfeeding WLWHIV who disengage from care are difficult to find in urban environments. Many have detectable viral loads, leading to the potential for an increased risk of MTCT. Efforts to reduce disengagement from care are critical for the successful elimination of MTCT in resource-limited settings.Item Pubertal Onset in HIV-infected Children in the Era of Combination Antiretroviral Treatment(Wolters Kluwer, 2013) Williams, Paige L.; Abzug, Mark J.; Jacobson, Denise L.; Wang, Jiajia; Van Dyke, Russell B.; Hazra, Rohan; Patel, Kunjal; Dimeglio, Linda A.; McFarland, Elizabeth J.; Silio, Margarita; Borkowsky, William; Seage, George R.; Oleske, James M.; Geffner, Mitchell E.; International Maternal Pediatric and Adolescent AIDS Clinical Trials P219219C Study; Pediatric HIVAIDS Cohort Study; Pediatrics, School of MedicineObjective: To evaluate associations of perinatal HIV infection, HIV disease severity, and combination antiretroviral treatment with age at pubertal onset. Design: Analysis of data from two US longitudinal cohort studies (IMPAACT 219C and PHACS AMP), conducted during 2000-2012, including perinatally HIV-infected (PHIV) and HIV-exposed but uninfected (HEU) youth. Tanner stage assessments of pubertal status (breast and pubic hair in girls; genitalia and pubic hair in boys) were conducted annually. Methods: We compared the timing of pubertal onset (Tanner stage ≥2) between PHIV and HEU youth using interval-censored models. For PHIV youth, we evaluated associations of HIV disease severity and combination antiretroviral treatment with age at pubertal onset, adjusting for race/ethnicity and birth cohort. Results: The mean age at pubertal onset was significantly later for the 2086 PHIV youth compared to the 453 HEU children (10.3 vs. 9.6, 10.5 vs. 10.0, 11.3 vs. 10.4, and 11.5 vs. 10.7 years according to female breast, female pubic hair, male genitalia, and male pubic hair staging, respectively, all P < 0.001). PHIV youth with HIV-1 RNA viral load above 10, 000 copies/ml (vs. ≤10, 000 copies/ml) or CD4% below 15% (vs. ≥15%) had significantly later pubertal onset (by 4-13 months). Each additional year of combination antiretroviral treatment was associated with a 0.6-1.2-month earlier mean age at pubertal onset, but this trend did not persist after adjustment for birth cohort. Conclusion: Pubertal onset occurs significantly later in PHIV than in HEU youth, especially among those with more severe HIV disease. However, in the current era, combination antiretroviral treatment may result in more normal timing of pubertal onset.