Changes in HIV-1 Subtypes B and C Genital Tract RNA in Women and Men After Initiation of Antiretroviral Therapy

Background. Combination antiretroviral therapy (cART) reduces genital tract human immunodeficiency virus type 1 (HIV-1) load and reduces the risk of sexual transmission, but little is known about the efficacy of cART for decreasing genital tract viral load (GTVL) and differences in sex or HIV-1 subtype

Infectious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Virus in Symptomatic Coronavirus Disease 2019 (COVID-19) Outpatients: Host, Disease, and Viral Correlates

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectious virus isolation in outpatients with coronavirus disease 2019 (COVID-19) has been associated with viral RNA levels and symptom duration, little is known about the host, disease, and viral determinants of infectious virus detection.COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay.Among 204 participants with mild-to-moderate symptomatic COVID-19, the median nasopharyngeal viral RNA was 6.5 (interquartile range [IQR] 4.7–7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (immunoglobulin (Ig)A, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (prevalence ratio [PR] = 0.12, 95% confidence interval [CI]: .04, .36; P = .00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; P < .0001) and fewer days since symptom onset (PR = 0.79, 95% CI: .71, .88 per day; P < .0001).The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion.NCT04405570

HIV Dynamics in Seminal Plasma during Primary HIV Infection

HIV dynamics in seminal plasma during primary HIV infection was evaluated through an observational study of individuals with primary HIV infection at the University of Washington Primary Infection Clinic. Seminal plasma HIV RNA was quantified using a real-time reverse transcription PCR assay. Blood plasma RNA was quantified by bDNA or PCR-based assays. Longitudinal analyses of HIV RNA levels over time used random effects regression analysis. From 1993 to 2005, 110 men collected 327 semen specimens. Initial blood and seminal plasma RNA levels in untreated men were only moderately correlated (Spearman r = 0.38, p = 0.0002). Estimated peak and set point levels were lower in semen than blood by 0.8 (p = 0.001) and 0.7 (p < 0.001) log10 copies/ml, respectively. RNA decay rates were similar in the two compartments (p = 0.4). For 2 months after infection, mean HIV RNA levels in seminal plasma remained above a threshold level (3.8 log10 copies/ml) that has been associated with recovery of infectious virus in vitro. HIV-positive men are likely to be most infectious in the first months following HIV acquisition. However, the modest relationship between HIV RNA levels in blood and seminal plasma suggests that the relative risk of HIV transmission during primary infection may vary from current estimates that are solely based on blood levels. Incorporating seminal plasma HIV levels into future mathematical models may increase the accuracy of these models

Median Log₁₀ HIV-1 RNA Level During the First Month of Antiretroviral Therapy among 13 Kenyan Men.

<p>P values given are for paired comparisons to baseline levels for each sample type.</p><p>IQR  =  Inter-quartile range.</p>*<p>Due to public holidays or other scheduling difficulties, eleven visits (15.9%) occurred one day before or one day after the scheduled visit date.</p>†<p>One day 7 visit was missed and two day 28 visits were missed. All semen samples were missing for one participant. Blood samples were missing on day 7 (2 samples) and day 14 (1 sample).</p

Decrease in HIV-1 RNA in blood and semen during the first month of antiretroviral therapy.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043086#pone-0043086-g001" target="_blank">Figure 1a</a> presents results for blood plasma, and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043086#pone-0043086-g001" target="_blank">Figure 1b</a> presents results for seminal plasma. Open, connected circles represent included data points (see methods). The bold line represents the modeled estimate. Delta (δ) is the estimate for the initial, rapid phase of decay, and mu (μ) the estimate for the subsequent, slower phase of decay. The half-life in days for each phase is equal to ln(2) divided by the decay rate in log₁₀ virions/day. P values are presented for comparisons of the two decay rates in seminal plasma to those seen in blood plasma. NA = not applicable.</p

Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) are among the treatments recommended for high-risk ambulatory persons with coronavirus 2019 (COVID-19). Here, we study viral culture dynamics post-treatment in a subset of participants receiving the mAb bamlanivimab in the ACTIV-2 trial (ClinicalTrials.gov: NCT04518410). Viral load by qPCR and viral culture are performed from anterior nasal swabs collected on study days 0 (day of treatment), 1, 2, 3, and 7. Treatment with mAbs results in rapid clearance of culturable virus. One day after treatment, 0 of 28 (0%) participants receiving mAbs and 16 of 39 (41%) receiving placebo still have culturable virus (p&nbsp;&lt;&nbsp;0.0001). Recrudescence of culturable virus is detected in three participants with emerging mAb resistance and viral RNA rebound. While further studies are necessary to fully define the relationship between shed culturable virus and transmission, these results raise the possibility that mAbs may offer immediate (household) and public-health benefits by reducing onward transmission