Browsing by Author "Lyagoba, Fred"

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    Lack of Effectiveness of Antiretroviral Therapy in Preventing HIV Infection in Serodiscordant Couples in Uganda: An Observational Study.
    (2015-07-14) Birungi, Josephine; Min, Jeong Eun; Muldoon, Katherine A.; Kaleebu, Pontiano; King, Rachel; Khanakwa, Sarah; Nyonyintono, Maureen; Chen, YaLin; Mills, Edward J.; Lyagoba, Fred; Ragonnet-Cronin, Manon; Wangisi, Jonathan; Lourenco, Lillian; Moore, David M.
    Background We examined the real-world effectiveness of ART as an HIV prevention tool among HIV serodiscordant couples in a programmatic setting in a low-income country. Methods We enrolled individuals from HIV serodiscordant couples aged >18 years of age in Jinja, Uganda from June 2009 – June 2011. In one group of couples the HIV positive partner was receiving ART as they met clinical eligibility criteria (a CD4 cell count >250 cells/ μL or WHO Stage III/IV disease). In the second group the infected partner was not yet ARTeligible. We measured HIV incidence by testing the uninfected partner every three months. We conducted genetic linkage studies to determine the source of new infections in seroconverting participants. Results A total of 586 couples were enrolled of which 249 (42%) of the HIV positive participants were receiving ART at enrollment, and an additional 99 (17%) initiated ART during the study. The median duration of follow-up was 1.5 years. We found 9 new infections among partners of participants who had been receiving ART for at least three months and 8 new infections in partners of participants who had not received ART or received it for less than three months, for incidence rates of 2.09 per 100 person-years (PYRs) and 2.30 per 100 PYRs, respectively. The incidence rate ratio for ART-use was 0.91 (95% confidence interval 0.31-2.70; p=0.999). The hazard ratio for HIV seroconversion associated with ART-use by the positive partner was 1.07 (95% CI 0.41-2.80). A total of 5/7 (71%) of the transmissions on ART and 6/7 (86%) of those not on ART were genetically linked. Conclusion Overall HIV incidence was low in comparison to previous studies of serodiscordant couples. However, ART-use was not associated with a reduced risk of HIV transmission in this study.
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    Short Communication HIV Type 1 Transmitted Drug Resistance and Evidence of Transmission Clusters among Recently Infected Antiretroviral-Naive Individuals from Ugandan Fishing Communities of Lake Victoria
    (Aids Research and Human Retroviruses, 2013) Nazziwa, Jamirah; Njai, Harr Freeya; Ndembi, Nicaise; Birungi, Josephine; Lyagoba, Fred; Gershim, Asiki; Nakiyingi-Miiro, Jessica; Nielsen, Leslie; Mpendo, Juliet; Nanvubya, Annet; Debont, Jan; Grosskurth, Heiner; Kamali, Anatoli; Seeley, Janet; Kaleebu, Pontiano
    Human immunodeficiency virus type 1 (HIV-1) prevalence and incidence in the fishing communities on Lake Victoria in Uganda are high. This population may play a role in driving the HIV epidemic in Uganda including the spread of transmitted drug resistance (TDR). We report data on TDR in this population among antiretroviral (ARV)-naive, recently infected individuals about 5 years after ARV scaling-up in Uganda. We identified phylogenetic transmission clusters and combined these with volunteer life histories in order to understand the sexual networks within this population. From a prospective cohort of 1,000 HIV-negative individuals recruited from five communities, 51 seroconverters were identified over a period of 2 years. From these, whole blood was collected and population sequencing of the HIV-1 pol gene (protease/reverse transcriptase) was performed from plasma. Drug resistance mutations (DRMs) were scored using the 2009 WHO list for surveillance of TDR. TDR prevalence categories were estimated using the WHO recommended truncated sampling technique for the surveillance of TDR for use in resource-limited settings (RLS). Of the samples 92% (47/51) were successfully genotyped. HIV-1 subtype frequencies were 15/47 (32%) A1, 20/47 (43%) D, 1/47 (2%) C, 1/47 (2%) G, and 10/ 47 (21%) unique recombinant forms. Nonnucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutation K103N was identified in two individuals and V106A in one (6%) suggesting that the level of TDR was moderate in this population. No nucleoside/tide reverse transcriptase inhibitor (NRTI) or protease inhibitor (PI) DRMs were detected. In this study, we identified five transmission clusters supported by high bootstrap values and low genetic distances. Of these, one pair included the two individuals with K103N. Two of the genotypic clusters corresponded with reported sexual partnerships as detected through prior in-depth interviews. The level of TDR to NNRTIs in these ARV-naive individuals was moderate by WHO threshold survey categorization. The transmission clusters suggest a high degree of sexual partner mixing between members of these communities.