Browsing by Author "Kalibbala, Sarah"
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Item Antiretroviral Therapy is Highly Effective Against Incident Hepatitis B Disease Acquisition Among HIV-Infected Adults in Rakai, Uganda(American Society of Clinical Oncology, 2016) Seremba, Emmanuel; Ssempijja, Victor; Kalibbala, Sarah; Gray, Ronald; Wawer, Maria; Nalugoda, Fred; Casper, Corey; Phipps, Warren T.; Ocama, Ponsiano; Thomas, David L.; Reynolds, Steven J.Co-infection with HepatitisB(HBV) and HIV iscommonin sub-Saharan Africa (SSA) and accelerates progression of liver disease to cirrhosis, hepatocellular carcinoma (HCC) andother complications. About 60% of HCC in Africa is attributed to HBV. In Uganda, 80% of HCC patients have HBVand20%have HIV/HBV coinfection.HCCis the 4th commonest cancer among Ugandan males and the 6th commonest in females. It is almost always a fatal malignancy in SSA. Prevention of HBV is best achieved through vaccination. Vaccination of HIV-infected adults for HBV is standard of care in developed countries but not in SSA where HBV is believed to be acquired in childhood and where there is lack of HBV incidence data. We investigated the incidence and risk factors associated with HBV among HIV-infected adults in Rakai, Uganda.Item Decreased Monocyte Activation with daily Acyclovir use in HIV-1/HSV-2 Coinfected Women(Sexually transmitted infections, 2015) Redd, Andrew D.; Nalugoda, Fred; Ssebbowa, Paschal; Kalibbala, SarahSeveral clinical trials have demonstrated that daily treatment of HIV-infected individuals with the antiherpes drug acyclovir slightly decreases HIV-1 viral load and slows disease progression. This study examines if this slowing in clinical progression is a direct cause of the decrease in viral load or an indirect effect of lower immune activation due to lower levels of herpetic reactivation. Women who participated in a randomised clinical trial of daily acyclovir use (n=301) were monitored every 6 months for changes in immune activation. Soluble CD14 (sCD14), a marker for monocyte activation, and C-reactive protein (CRP), a marker for general immune activation, were measured by ELISA.Initial levels of sCD14 and CRP were not predictive of HIV disease progression when controlling for initial CD4+ cell count and HIV viral load. sCD14 levels, but not CRP, decreased in the acyclovir treatment arm at a significantly faster rate than the placebo group, which was independent of changes in HIV viral load and CD4+ cell count in a multivariant mixed-effects model (p=0.039). However, the magnitude of this decrease was relatively small with a total estimated decrease of sCD14 of 15% of initial levels.These data suggest that decreased monocyte activation may play a minor role in the ability of daily acyclovir use to slow HIV disease progression.Item The Effect of Antiretroviral Therapy Initiation on the Vaginal Microbiome in HIV-Infected Women(The Journal of infectious diseases, 2021) Liu, Cindy M.; Packman, Zoe R.; Abraham, Alison G.; Serwadda, David M.; Nalugoda, Fred; Aziz, Maliha; Prodger, Jessica L.; Kaul, Rupert; Kalibbala, Sarah; Gray, Ronald H.; Price, Lance B.; Quinn, Thomas C.; Tobian, Aaron A.R.; Reynolds, Steven J.The impact of antiretroviral therapy (ART) initiation on the vaginal microbiome is unknown. This is of particular importance among women living in sub-Saharan Africa. Understanding this relationship could help elucidate if and how the host immune system interacts with the vaginal microbiome. Methods. The vaginal microbiome of HIV-1/HSV-2-coinfected women (n = 92) in Uganda was evaluated from self-collected vaginal swabs 1 month pre-ART and at 4 and 6 months post–ART initiation. The vaginal microbiome was characterized by 16S rRNA genebased sequencing and quantitative polymerase chain reaction. Vaginal community state types (CSTs) were identified using proportional abundance data. Changes in microbiome composition were assessed with permutational analyses of variance (PerMANOVA).Item Evaluation of current rapid HIV test algorithms in Rakai, Uganda(Journal of virological methods, 2013) Galiwango, Ronald M.; Musoke, Richard; Lubyayi, Lawrence; Ssekubugu, Robert; Kalibbala, Sarah; Ssekweyama, Viola; Mirembe, Viola; Nakigozi, Gertrude; Reynolds, Steven J.; Serwadda, David; Gray, Ronald H.; Kigozi, GodfreyRapid HIV tests are a crucial component of HIV diagnosis in resource limited settings. In Uganda, the Ministry of Health allows for both serial and parallel HIV rapid testing using Determine, Stat- Pak and Uni-Gold. In serial testing, a non-reactive result on Determine ends testing. The performance of serial and parallel algorithms with Determine and Stat-Pak test kits was assessed. A cross-sectional diagnostic test accuracy evaluation using three rapid HIV test kits as per the recommended parallel test algorithm was followed by EIA-WB testing with estimates of the performance of serial testing algorithm. In 2520 participants tested by parallel rapid algorithms, 0.6% had weakly reactive result. Parallel testing had 99.7% sensitivity and 99.8% specificity. If Stat-Pak was used as the first screening test for a serial algorithm, the sensitivity was 99.6% and specificity 99.7%. However, if Determine was used as the screening test, sensitivity was 97.3% and specificity 99.9%. Serial testing with Stat-Pak as the initial screening test performed as well as parallel testing, but Determine was a less sensitive screen. Serial testing could be cost saving.Item HIV serologically indeterminate individuals: Future HIV status and risk factors(PLoS ONE, 2020) Mwinnyaa, George; Grabowski, Mary K.; Gray, Ronald H.; Wawer, Maria; Chang, Larry W.; Ssekasanvu, Joseph; Kagaayi, Joseph; Kigozi, Godfrey; Kalibbala, Sarah; Galiwango, Ronald M.; Ndyanabo, Anthony; Serwadda, David; Quinn, Thomas C.; Reynolds, Steven J.; Laeyendecker, OliverIndeterminate HIV test results are common, but little is known about the evolution of indeterminate serology and itssociodemographic and behavioral correlates. We assessed future HIV serological outcomes for individuals with indeterminate results and associated factors in Rakai, Uganda. Methods 115,944 serological results, defined by two enzyme immunoassay (EIAs), among 39,440 individuals aged 15–49 years in the Rakai Community Cohort Study were assessed. Indeterminate results were defined as contradictory EIAs. Modified Poisson regression models with generalized estimating equations were used to assess prevalence ratios (PRs) of subsequent HIV serological outcomes and factors associated with HIV indeterminate results.Item Immunological Signaling During Herpes Simplex Virus-2 and Cytomegalovirus Vaginal Shedding After Initiation of Antiretroviral Treatment(Oxford University Press, 2016) Nason, Martha C.; Patel, Eshan U.; Kirkpatrick, Allison R.; Prodger, Jessica L.; Shahabi, Kamnoosh; Tobian, Aaron A. R.; Gianella, Sara; Kalibbala, Sarah; Ssebbowa, Paschal; Kaul, Rupert; Gray, Ronald H.; Quinn, Thomas C.; Serwadda, David; Reynolds, Steven J.; Redd, Andrew D.Vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus infected women before and after initiation of antiretroviral therapy (ART). Vaginal swabs were screened for levels of cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)-α, and interferon- γ. The relative risk (RR) of herpes simplex virus-2 or cytomegalovirus (CMV) shedding being associated with cytokine levels above the median were estimated. Herpes simplex virus-2 shedding was significantly associated with higher levels of IL-6 (RR = 1.4, P = .003) and TNF-α (RR = 1.3, P = .010), whereas CMV shedding was associated with higher IL-6 (RR = 1.3, P = .006) and IL-2 (RR = 1.4, P = .01). The association of viral shedding with higher IL-6 levels suggests that herpes virus reactivation may be playing a role in immune activation after ART initiation.Item Prevalence and Predictors of Persistent Human Immunodeficiency Virus Viremia and Viral Rebound After Universal Test and Treat: A Population-Based Study(The Journal of infectious diseases, 2021) Grabowski, M. Kate; Patel, Eshan U.; Nakigozi, Gertrude; Ssempijja, Victor; Ssekubugu, Robert; Ssekasanvu, Joseph; Ndyanabo, Anthony; Kigozi, Godfrey; Nalugoda, Fred; Gray, Ronald H.; Kalibbala, Sarah; Serwadda, David M.; Laeyendecker, Oliver; Wawer, Maria J.; Chang, Larry W.; Quinn, Thomas C.; Kagaayi, Joseph; Tobian, Aaron A. R.; Reynolds, Steven J.UNAIDS targets for human immunodeficiency virus (HIV) epidemic control by 2030 include that 86% of all HIV-positive persons be on antiretroviral therapy (ART) and achieve HIV viral load (VL) suppression [1]. The major policy initiative underpinning this target is universal test and treat (UTT), whereby all HIV-positive persons, irrespective of CD4 count or severity of illness, are immediately prescribed ART [2]. In sub-Saharan Africa, which accounts for more than half of all new HIV diagnoses globally, there has been considerable progress in increasing ART coverage [Item Quantifying HIV transmission flow between high-prevalence hotspots and surrounding communities: a population-based study in Rakai, Uganda(The Lancet HIV, 2020) Ratmann, Oliver; Kagaayi, Joseph; Hall, Matthew; Golubchick, Tanya; Kigozi, Godfrey; Nakigozi, Gertrude; Bazaale, Jeremiah; Kalibbala, Sarah; Nalugoda, Fred; Ssekubugu, Robert; Serwadda, DavidInternational and global organisations advocate targeting interventions to areas of high HIV prevalence (ie, hotspots). To better understand the potential benefits of geo-targeted control, we assessed the extent to which HIV hotspots along Lake Victoria sustain transmission in neighbouring populations in south-central Uganda. Methods We did a population-based survey in Rakai, Uganda, using data from the Rakai Community Cohort Study. The study surveyed all individuals aged 15–49 years in four high-prevalence Lake Victoria fishing communities and 36 neighbouring inland communities. Viral RNA was deep sequenced from participants infected with HIV who were antiretroviral therapy-naive during the observation period. Phylogenetic analysis was used to infer partial HIV transmission networks, including direction of transmission. Reconstructed networks were interpreted through data for current residence and migration history. HIV transmission flows within and between high-prevalence and low-prevalence areas were quantified adjusting for incomplete sampling of the population. Findings Between Aug 10, 2011, and Jan 30, 2015, data were collected for the Rakai Community Cohort Study. 25 882 individuals participated, including an estimated 75·7% of the lakeside population and 16·2% of the inland population in the Rakai region of Uganda. 5142 participants were HIV-positive (2703 [13·7%] in inland and 2439 [40·1%] in fishing communities). 3878 (75·4%) people who were HIV-positive did not report antiretroviral therapy use, of whom 2652 (68·4%) had virus deep-sequenced at sufficient quality for phylogenetic analysis. 446 transmission networks were reconstructed, including 293 linked pairs with inferred direction of transmission. Adjusting for incomplete sampling, an estimated 5·7% (95% credibility interval 4·4–7·3) of transmissions occurred within lakeside areas, 89·2% (86·0–91·8) within inland areas, 1·3% (0·6–2·6) from lakeside to inland areas, and 3·7% (2·3–5·8) from inland to lakeside areas.Item Vaginal Cytomegalovirus Shedding Before and After Initiation of Antiretroviral Therapy in Rakai, Uganda(The Journal of infectious diseases, 2015) Gianella, Sara; Redd, Andrew D.; Grabowski, Mary K.; Tobian, Aaron A. R.; Serwadda, David; Newell, Kevin; Patel, Eshan U.; Kalibbala, Sarah; Ssebbowa, Paschal; Gray, Ronald H.; Quinn, Thomas C.; Reynolds, Steven J.Vaginal shedding of cytomegalovirus (CMV) DNA was determined longitudinally among 96 women coinfected with human immunodeficiency virus (HIV), herpes simplex virus 2, and CMV starting antiretroviral therapy (ART) during a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Vaginal CMV was detected in 75 of 96 women (78.0%) and 379 of 1080 individual visits (35.1%). ART status, higher HIV RNAviral load before ART initiation, and younger age were significantly associated with increased frequency of CMV shedding (P < .01). Compared to pre- ART, CMV shedding peaked from month 2 to month 4 after ART initiation, suggesting possible immune reconstitution inflammatory syndrome. Further studies need to determine the clinical significance of asymptomatic CMV shedding.