Effect of Treatment of Asymptomatic Bacterial Vaginosis on HIV‐1 Shedding in the Genital Tract among Women on Antiretroviral Therapy: A Pilot Study

Abstract Background: Antiretroviral therapy for HIV-1 infection has become increasingly complex. The availability of new and potent drugs and progress in understanding the pathogenesis of HIV-1 infection have led to the establishment of new treatment paradigms. The varying dosing regimens, associated toxicities, and the potential for drug-drug and food-drug interactions further complicate treatment. This complexity contributes to patient nonadherence. Because clinicians have no tools to monitor adherence or drug-drug interactions and because response requires that therapy exceed the known inhibiting concentration, serum monitoring of antiretroviral therapy may play a role in improving treatment of HIV-1 infection. We report methods to quantify serum concentrations of antiretroviral drugs used to treat HIV-1 infection, precision and interference studies of these methods, and results observed in a pilot evaluation of blood serum concentrations from 12 human subjects. Methods: HPLC offers adequate sensitivity to measure peak or trough serum concentrations of delavirdine, lamivudine, nevirapine, indinavir, nelfinavir, ritonavir, and saquinavir and peak serum concentrations of stavudine, zidovudine, and didanosine with reasonable precision. Results: Peak indinavir serum concentrations in most patients were in the range of 1–10 mg/L, and trough concentrations were in the range of 0.1–0.5 mg/L. Peak stavudine concentrations were in the range of 0.3–1.3 mg/L, and trough concentrations were in the range of 0.1–0.5 mg/L. Peak zidovudine concentrations were in the range of 0.1–1.1 mg/L. Conclusions: Because this was a blood serum concentration-seeking pilot study to evaluate analytic performance, we do not report on the correlation of drug response to blood concentration. However, the concentrations observed in patients are generally consistent with blood concentrations reported from studies of monotherapy.

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Bacterial Vaginosis–Associated Microflora Isolated From the Female Genital Tract Activates HIV-1 Expression

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/00126334-199907010-00003 ◽

1999 ◽

Vol 21 (3) ◽

pp. 194 ◽

Cited By ~ 52

Author(s):

Lena Al-Harthi ◽

Kenneth A. Roebuck ◽

Gene G. Olinger ◽

Alan Landay ◽

Beverly E. Sha ◽

...

Keyword(s):

Bacterial Vaginosis ◽

Genital Tract ◽

Female Genital Tract ◽

Hiv 1 ◽

Female Genital

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Association of indicators of bacterial vaginosis with a female genital tract factor that induces expression of HIV-1

AIDS ◽

10.1097/00002030-199910010-00013 ◽

1999 ◽

Vol 13 (14) ◽

pp. 1905-1912 ◽

Cited By ~ 24

Author(s):

Gene G. Olinger ◽

Farhad B. Hashemi ◽

Beverly E. Sha ◽

Gregory T. Spear

Keyword(s):

Bacterial Vaginosis ◽

Genital Tract ◽

Female Genital Tract ◽

Hiv 1 ◽

Female Genital

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Directly observed antiretroviral therapy to reduce genital tract and plasma HIV-1 RNA in women with poor adherence

AIDS ◽

10.1097/00002030-200309050-00021 ◽

2003 ◽

Vol 17 (13) ◽

pp. 1990-1993 ◽

Cited By ~ 6

Author(s):

Joseph I Harwell ◽

Timothy P Flanigan ◽

Jennifer A Mitty ◽

Grace E Macalino ◽

Angela M Caliendo ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Genital Tract ◽

Poor Adherence ◽

Hiv 1

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Noninferiority of Simplified Dolutegravir Monotherapy Compared to Continued Combination Antiretroviral Therapy That Was Initiated During Primary Human Immunodeficiency Virus Infection: A Randomized, Controlled, Multisite, Open-label, Noninferiority Trial

Clinical Infectious Diseases ◽

10.1093/cid/ciy1131 ◽

2019 ◽

Vol 69 (9) ◽

pp. 1489-1497 ◽

Cited By ~ 5

Author(s):

Dominique L Braun ◽

Teja Turk ◽

Fabian Tschumi ◽

Christina Grube ◽

Benjamin Hampel ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Antiretroviral Therapy ◽

Pilot Study ◽

Latent Reservoir ◽

Combination Antiretroviral Therapy ◽

Open Label ◽

Once Daily ◽

Noninferiority Trial ◽

Immunodeficiency Virus ◽

Hiv 1

Abstract Background Patients who start combination antiretroviral therapy (cART) during primary human immunodeficiency virus type 1 (HIV-1) infection show a smaller HIV-1 latent reservoir, less immune activation, and less viral diversity compared to patients who start cART during chronic infection. We conducted a pilot study to determine whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir monotherapy. Methods EARLY-SIMPLIFIED is a randomized, open-label, noninferiority trial. Patients who started cART <180 days after a documented primary HIV-1 infection and had an HIV-1 RNA <50 copies/mL plasma for at least 48 weeks were randomized (2:1) to monotherapy with dolutegravir 50 mg once daily or to continuation of cART. The primary efficacy endpoint was the proportion of patients with <50 HIV-1 RNA copies/mL on or before week 48; noninferiority margin 10%. Results Of the 101 patients randomized, 68 were assigned to simplification to dolutegravir monotherapy and 33 to continuation of cART. At week 48 in the per-protocol population, 67/67 (100%) had virological response in the dolutegravir monotherapy group vs 32/32 (100%) in the cART group (difference, 0.00%; 95% confidence interval, –100%, 4.76%). This showed noninferiority of the dolutegravir monotherapy at the prespecified level. Conclusion In this pilot study consisting of patients who initiated cART during primary HIV-1 infection and had <50 HIV-1 RNA copies/mL for at least 48 weeks, monotherapy with once-daily dolutegravir was noninferior to cART. Our results suggest that future simplification studies should use a stratification according to time of HIV infection and start of first cART. Clinical Trials Registration NCT02551523.

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Faculty Opinions recommendation of Aspirin attenuates platelet activation and immune activation in HIV-1-infected subjects on antiretroviral therapy: a pilot study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717978778.793473200 ◽

2013 ◽

Author(s):

Gene Shearer ◽

Adriano Boasso

Keyword(s):

Antiretroviral Therapy ◽

Pilot Study ◽

Platelet Activation ◽

Immune Activation ◽

Hiv 1

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Etravirine Concentrations in the Cervicovaginal Compartment in HIV-1-Infected Women Receiving Etravirine-Containing Antiretroviral Therapy: DIVA 02 Study

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.06474-11 ◽

2012 ◽

Vol 56 (7) ◽

pp. 4018-4020 ◽

Cited By ~ 9

Author(s):

C. Clavel ◽

G. Peytavin ◽

R. Tubiana ◽

C. Soulié ◽

E. Courbon ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Viral Replication ◽

Blood Plasma ◽

Genital Tract ◽

Female Genital Tract ◽

Hiv Rna ◽

Good Penetration ◽

Hiv 1 ◽

Cervicovaginal Fluid ◽

Female Genital

ABSTRACTWe studied the penetration of etravirine and HIV shedding in the genital tract among 12 HIV-1-infected women receiving an etravirine-containing regimen who had <40 copies/ml blood plasma (BP) HIV RNA. None of the cervicovaginal fluid (CVF) samples showed detectable HIV RNA. Median etravirine concentrations were 663 ng/ml in BP and 857 ng/ml in CVF, with a CVF/BP etravirine ratio of approximately 1.2. This good penetration of etravirine may contribute to the control of viral replication in the female genital tract.

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