Long-term hepatitis B virus (HBV) response to lamivudine-containing highly active antiretroviral therapy in HIV-HBV co-infected patients in Thailand

Woottichai Khamduang, Catherine Gaudy-Graffin, Nicole Ngo-Giang-Huong, Gonzague Jourdain, Alain Moreau, Nuananong Luekamlung, Guttiga Halue, Yuwadee Buranawanitchakorn, Sura Kunkongkapan, Sudanee Buranabanjasatean, Marc Lallemant, Wasna Sirirungsi, Alain Goudeau, Program for HIV Prevention and Treatment Study Group, Prattana Leenasirimakul, Sudanee Buranabanjasatean, Chureeratana Bowonwatanuwong, Pacharee Kantipong, Rattakarn Paramee, Sukit Banchongkit, Sinart Prommas, Somboon Tansuphasawasdikul, Malee Techapornroong, Pakorn Wittayapraparat, Surachai Pipatnakulchai, Ampaipith Nilmanat, Naruepon Yutthakasemsunt, Apichat Chutanunta, Pensiriwan Sang-a-gad, Guttiga Halue, Nuananong Luekamlung, Virat Klinbuayaem, Doi Saket, Preecha Sirichithaporn, Maharaj Nakornratchasrima, Rittha Lertkoonalak, Suchart Thongpaen, Khon Kaen, Kraisorn Vivatpatanakul, Nopporn Pattanapornpun, Worawut Cowatcharagul, Naree Eiamsirikit, Panita Pathipvanich, Rapat Pittayanon, Chiang Kham, Yuwadee Buranawanitchakorn, Sookchai Theansavettrakul, Khon Kaen, Janyaporn Ratanakosol, Somdej Prapinklao, Pasri Maharom, Patinun Chirawatthanaphan, Kranuan Crown Prince, Amporn Rattanaparinya, Boonyong Jeerasuwannakul, Nopparat Rajathanee, Jeerapat Wongchinsri, Prateep Kanjanavikai, Narongdej Pipattanawong, Woottichai Khamduang, Catherine Gaudy-Graffin, Nicole Ngo-Giang-Huong, Gonzague Jourdain, Alain Moreau, Nuananong Luekamlung, Guttiga Halue, Yuwadee Buranawanitchakorn, Sura Kunkongkapan, Sudanee Buranabanjasatean, Marc Lallemant, Wasna Sirirungsi, Alain Goudeau, Program for HIV Prevention and Treatment Study Group, Prattana Leenasirimakul, Sudanee Buranabanjasatean, Chureeratana Bowonwatanuwong, Pacharee Kantipong, Rattakarn Paramee, Sukit Banchongkit, Sinart Prommas, Somboon Tansuphasawasdikul, Malee Techapornroong, Pakorn Wittayapraparat, Surachai Pipatnakulchai, Ampaipith Nilmanat, Naruepon Yutthakasemsunt, Apichat Chutanunta, Pensiriwan Sang-a-gad, Guttiga Halue, Nuananong Luekamlung, Virat Klinbuayaem, Doi Saket, Preecha Sirichithaporn, Maharaj Nakornratchasrima, Rittha Lertkoonalak, Suchart Thongpaen, Khon Kaen, Kraisorn Vivatpatanakul, Nopporn Pattanapornpun, Worawut Cowatcharagul, Naree Eiamsirikit, Panita Pathipvanich, Rapat Pittayanon, Chiang Kham, Yuwadee Buranawanitchakorn, Sookchai Theansavettrakul, Khon Kaen, Janyaporn Ratanakosol, Somdej Prapinklao, Pasri Maharom, Patinun Chirawatthanaphan, Kranuan Crown Prince, Amporn Rattanaparinya, Boonyong Jeerasuwannakul, Nopparat Rajathanee, Jeerapat Wongchinsri, Prateep Kanjanavikai, Narongdej Pipattanawong

Abstract

Background: Approximately 4 million of people are co-infected with HIV and Hepatitis B virus (HBV). In resource-limited settings, the majority of HIV-infected patients initiate first-line highly active antiretroviral therapy containing lamivudine (3TC-containing-HAART) and long-term virological response of HBV to lamivudine-containing HAART in co-infected patients is not well known.

Methodology/principal finding: HIV-HBV co-infected patients enrolled in the PHPT cohort (ClinicalTrials.gov NCT00433030) and initiating a 3TC-containing-HAART regimen were included. HBV-DNA, HIV-RNA, CD4+ T-cell counts and alanine transaminase were measured at baseline, 3 months, 12 months and then every 6 months up to 5 years. Kaplan-Meier analysis was used to estimate the cumulative rates of patients who achieved and maintained HBV-DNA suppression. Of 30 co-infected patients, 19 were positive for HBe antigen (HBeAg). At initiation of 3TC-containing-HAART, median HBV DNA and HIV RNA levels were 7.35 log(10) IU/mL and 4.47 log(10) copies/mL, respectively. At 12 months, 67% of patients achieved HBV DNA suppression: 100% of HBeAg-negative patients and 47% of HBeAg-positive. Seventy-three percent of patients had HIV RNA below 50 copies/mL. The cumulative rates of maintained HBV-DNA suppression among the 23 patients who achieved HBV-DNA suppression were 91%, 87%, and 80% at 1, 2, and 4 years respectively. Of 17 patients who maintained HBV-DNA suppression while still on 3TC, 4 (24%) lost HBsAg and 7 of 8 (88%) HBeAg-positive patients lost HBeAg at their last visit (median duration, 59 months). HBV breakthrough was observed only in HBeAg-positive patients and 6 of 7 patients presenting HBV breakthrough had the rtM204I/V mutations associated with 3TC resistance along with rtL180M and/or rtV173L.

Conclusions: All HBeAg-negative patients and 63% of HBeAg-positive HIV-HBV co-infected patients achieved long-term HBV DNA suppression while on 3TC-containing-HAART. This study provides information useful for the management of co-infected patients in resource-limited countries where the vast majority of co-infected patients are currently receiving 3TC.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Disposition of patients included in…
Figure 1. Disposition of patients included in this study.
Figure 2. HBV DNA and HIV RNA…
Figure 2. HBV DNA and HIV RNA load in HIV-HBV co-infected patients after initiation of 3TC-containing-HAART.
Dotted line indicates the lower limit of detection for HBV DNA (2.18 log10 IU/mL).
Figure 3. Kaplan-Meier curve of time to…
Figure 3. Kaplan-Meier curve of time to loss of HBV DNA suppression in 23 HIV-HBV co-infected patients who had achieved HBV DNA suppression during the course of 3TC-containing-HAART.
Figure 4. Serum ALT level and CD4+…
Figure 4. Serum ALT level and CD4+ T-cells count in HIV-HBV co-infected patients after initiation of 3TC-containing-HAART.

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Source: PubMed

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