Multiple HIV-1 infections with evidence of recombination in heterosexual partnerships in a low risk Rural Clinical Cohort in Uganda.

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Transmitted Antiretroviral Drug Resistance among drug-naïve Commercial Sex Workers with recent infection in Kampala Uganda.

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DeMarino Pleet Cowen Barclay Akpamagbo Erickson Ndembi Charurat Jumare Kashanchi

Sci Rep.

To date, the most effective treatment of HIV-1 is a combination antiretroviral therapy (cART), which reduces viral replication and reverses pathology. We investigated the effect of cART (RT and protease inhibitors) on the content of extracellular vesicles (EVs) released from HIV-1-infected cells. We have previously shown that EVs contain non-coding HIV-1 RNA, which can elicit responses in recipient cells. In this manuscript, we show that TAR RNA levels demonstrate little change with the addition of cART treatment in cell lines, primary macrophages, and patient biofluids. We determined possible mechanisms involved in the selective packaging of HIV-1 RNA into EVs, specifically an increase in EV-associated hnRNP A2/B1. More recent experiments have shown that several other FDA-approved drugs have the ability to alter the content of exosomes released from HIV-1-infected cells. These findings on cART-altered EV content can also be applied to general viral inhibitors (interferons) which are used to treat other chronic infections. Additionally, we describe unique mechanisms of ESCRT pathway manipulation by antivirals, specifically the targeting of VPS4. Collectively, these data imply that, despite antiretroviral therapy, EVs containing viral products are continually released and may cause neurocognitive and immunological dysfunction.

0018-05-28

Chaplin Akanmu Inzaule Samuels Okonkwo Ilesanmi Adewole Asadu Khamofu Mpazanje Ndembi

J Antimicrob Chemother.

Background: Many lines of evidence point to HIV-1 subtype-specific differences in
the development of drug resistance mutations. While variation between subtype C
and others has been extensively explored, there has been less emphasis on
subtypes common to West Africa. We examined a previously described national
survey of pretreatment drug resistance in HIV-1-infected Nigerian children aged
<18 months, to explore the association between subtypes and patterns of
resistance.
Methods: Five hundred and forty-nine dried blood spots, from 15 early infant
diagnostic facilities in Nigeria, were amplified and HIV-1 polymerase was
sequenced. Four hundred and twenty-four were analysed for surveillance drug
resistance mutations (SDRMs). Associations between subtype and SDRMs were
evaluated by Fisher's exact test and logistic regression analysis, controlling
for geographical region and exposure.
Results: Using the sub-subtypes of HIV-1 G defined by Delatorre et al. (PLoS One
2014.
9: e98908) the most common subtypes were CRF02_AG (174, 41.0%), GWA-I (128,
30.2%), GWA-II (24, 5.7%), GCA (11, 2.6%), A (21, 5.0%) and CRF06_cpx (18, 4.2%).
One hundred and ninety infants (44.8%) had ≥1 NNRTI mutation, 92 infants (21.7%)
had ≥1 NRTI mutation and 6 infants (1.4%) had ≥1 PI mutation. By logistic
regression, 67N was more common in GWA-II/GCA than CRF02_AG (OR 12.0, P = 0.006),
as was 70R (OR 23.1, P = 0.007), 184I/V (OR 2.92, P = 0.020), the presence of ≥1
thymidine analogue mutation (TAM) (OR 3.87, P = 0.014), ≥1 type 2 TAM (OR 7.61,
P = 0.001) and ≥1 NRTI mutation (OR 3.26, P = 0.005).
Conclusions: This dataset reveals differences among SDRMs by subtype; in
particular, between the GWA-II and GCA subclades, compared with CRF02_AG and
GWA-I.

2019-01-01

HIV-1 subtype distribution multiple infections sexual networks and partnership histories in Commercial Sex Workers in Kampala Uganda.

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Transmitted antiretroviral drug resistance among newly HIV-1 diagnosed young individuals in Kampala.

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