Human immunodeficiency virus and human papillomavirus infections in Mozambique : from epidemiological reports to clinical trials and vaccine implementation
Author: Viegas, Edna Omar
Date: 2017-09-29
Location: Lecture Hall, Hillarp, Retzius väg 8, Karolinska Institutet, Solna
Time: 09.00
Department: Inst för laboratoriemedicin / Dept of Laboratory Medicine
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Thesis (5.533Mb)
Abstract
Human immunodeficiency virus (HIV) and human papillomavirus (HPV) are sexually transmitted
microorganisms responsible for two major infectious diseases and public health concerns,
particularly in developing countries and in sub-Saharan Africa. HIV is the causative agent of the
acquired immunodeficiency syndrome (AIDS) that has so far claimed more than 35 million lives.
HPV is responsible for virtually all cervical cancers (CC), the seventh most common cancer in the
world and the fourth in women. Mozambique is highly affected by both HIV and HPV epidemics.
The country has the fifth highest prevalence of HIV in the world and the second highest rates of CC
in Africa. The national seroprevalence of HIV in 2015 was estimated to be 13.2% in populations
aged 15-49 years. A previous report from Southern Mozambique has demonstrated a high
prevalence of HPV in women aged 14-61 years (75.9%).
This thesis aimed at describing the epidemiology of HIV and HPV infections in young adults in Maputo city, Mozambique and to evaluate preventive strategies for control of HIV and HPV. This thesis embraces a total of four studies (I-IV). Study I aimed at determining the HIV incidence in youths aged 18-24 years. In this study 1380 subjects were screened for HIV, hepatitis B virus and syphilis. HIV-uninfected individuals (n=1309) were prospectively followed for one year with quarterly study visits to determine the HIV status. The HIV, hepatitis B and syphilis prevalence found at baseline were 5.1%, 12.2% and 0.36%, respectively. The overall HIV incidence was 1.14/100 PY and was slightly higher in the female population (1.49/100 WY). The relatively low prevalence and incidence of HIV and the low prevalence of syphilis described in this study associated to the considerable stable visit retention rates, suggest that this cohort is suitable for recruitment into phase I/II HIV vaccine trials. Study II was a phase I HIV vaccine trial that recruited 24 healthy HIV-uninfected individuals from the cohort established in study I and aimed at exploring the safety and immunogenicity of an HIV-DNA/HIV-MVA prime-boost strategy using a low-dose (600 μg, 2 x 0.1 mL) and a high-dose (1200 μg, 2 x 0.2 mL) of HIV-DNA prime, delivered intradermally using a needle-free device, the ZetajetTM. This was the first HIV vaccine trial ever conducted in Mozambique and the first to assess the use of the ZetajetTM in a higher injection volume. The vaccines were safe and well tolerated. After the first HIV-MVA, Env responses were significantly higher in the high-dose group compared to the low-dose group (median 420 vs. 157.5 SFC/million PBMC, p = 0.014). Four weeks after the 2nd HIV-MVA, binding antibodies to recombinant CN54 subtype C gp140 and to native subtype B gp160 were induced in all vaccinees, with a median titer of 800 and 400, respectively. The findings suggest that the higher 1200 μg HIV-DNA dose should be considered in the future. Study III describes HPV genotypes in young women and men recruited from the cohort established in study I. Cervical and urethral samples were collected in women and men, respectively and analyzed using the Clart® Human Papillomavirus 2 (Genomica, Madrid, Spain), a target amplification assay capable of detecting 35 different low- and high-risk HPV genotypes. The overall prevalence of HPV was 40.8% (63.6% and 10.2% in women and men, respectively). In women HPV52, 35, 16, 53, 58, 6, and 51 were the most frequently found genotypes and HPV6, 11, 52, 59, and 70 in men. These results show a 50% homology with the genotypes detected in CC specimens in the country. Study IV was a two-round post-vaccination survey conducted after an HPV vaccine demonstration project (in 2014 and 2015), in which an HPV vaccine was given to girls aged 9-10 years, in two rural districts of Mozambique (Manica and Mocímboa da Praia). This study aimed at assessing the HPV vaccine coverage, awareness, knowledge, and acceptance; to explore reasons for not-vaccinating; and to identify the best vaccine communication strategies. Parents or guardians of girls eligible for vaccination were interviewed within 4 months after the last HPV injection had been administered to the girls. Vaccine coverage in 2014 was 50% and 14% and in 2015 was 47% and 32% for Manica and Mocímboa da Praia, respectively. The most frequent reason to vaccinate the girls was the belief that the vaccine could contribute to the girl´s health. The reasons for not vaccinating were the absence of girls from school and the lack of knowledge about the campaign. The radio spot was the communication strategy that reached the majority of respondents. These results show that provision of information about the benefits of vaccines can lead to a positive decision by the parents/guardians and improved planning and communications may increase the vaccination rates. Lessons learned from this study may give important insights on the implementation of a future HIV vaccine in adolescents, a group that will most likely be prioritized.
This thesis aimed at describing the epidemiology of HIV and HPV infections in young adults in Maputo city, Mozambique and to evaluate preventive strategies for control of HIV and HPV. This thesis embraces a total of four studies (I-IV). Study I aimed at determining the HIV incidence in youths aged 18-24 years. In this study 1380 subjects were screened for HIV, hepatitis B virus and syphilis. HIV-uninfected individuals (n=1309) were prospectively followed for one year with quarterly study visits to determine the HIV status. The HIV, hepatitis B and syphilis prevalence found at baseline were 5.1%, 12.2% and 0.36%, respectively. The overall HIV incidence was 1.14/100 PY and was slightly higher in the female population (1.49/100 WY). The relatively low prevalence and incidence of HIV and the low prevalence of syphilis described in this study associated to the considerable stable visit retention rates, suggest that this cohort is suitable for recruitment into phase I/II HIV vaccine trials. Study II was a phase I HIV vaccine trial that recruited 24 healthy HIV-uninfected individuals from the cohort established in study I and aimed at exploring the safety and immunogenicity of an HIV-DNA/HIV-MVA prime-boost strategy using a low-dose (600 μg, 2 x 0.1 mL) and a high-dose (1200 μg, 2 x 0.2 mL) of HIV-DNA prime, delivered intradermally using a needle-free device, the ZetajetTM. This was the first HIV vaccine trial ever conducted in Mozambique and the first to assess the use of the ZetajetTM in a higher injection volume. The vaccines were safe and well tolerated. After the first HIV-MVA, Env responses were significantly higher in the high-dose group compared to the low-dose group (median 420 vs. 157.5 SFC/million PBMC, p = 0.014). Four weeks after the 2nd HIV-MVA, binding antibodies to recombinant CN54 subtype C gp140 and to native subtype B gp160 were induced in all vaccinees, with a median titer of 800 and 400, respectively. The findings suggest that the higher 1200 μg HIV-DNA dose should be considered in the future. Study III describes HPV genotypes in young women and men recruited from the cohort established in study I. Cervical and urethral samples were collected in women and men, respectively and analyzed using the Clart® Human Papillomavirus 2 (Genomica, Madrid, Spain), a target amplification assay capable of detecting 35 different low- and high-risk HPV genotypes. The overall prevalence of HPV was 40.8% (63.6% and 10.2% in women and men, respectively). In women HPV52, 35, 16, 53, 58, 6, and 51 were the most frequently found genotypes and HPV6, 11, 52, 59, and 70 in men. These results show a 50% homology with the genotypes detected in CC specimens in the country. Study IV was a two-round post-vaccination survey conducted after an HPV vaccine demonstration project (in 2014 and 2015), in which an HPV vaccine was given to girls aged 9-10 years, in two rural districts of Mozambique (Manica and Mocímboa da Praia). This study aimed at assessing the HPV vaccine coverage, awareness, knowledge, and acceptance; to explore reasons for not-vaccinating; and to identify the best vaccine communication strategies. Parents or guardians of girls eligible for vaccination were interviewed within 4 months after the last HPV injection had been administered to the girls. Vaccine coverage in 2014 was 50% and 14% and in 2015 was 47% and 32% for Manica and Mocímboa da Praia, respectively. The most frequent reason to vaccinate the girls was the belief that the vaccine could contribute to the girl´s health. The reasons for not vaccinating were the absence of girls from school and the lack of knowledge about the campaign. The radio spot was the communication strategy that reached the majority of respondents. These results show that provision of information about the benefits of vaccines can lead to a positive decision by the parents/guardians and improved planning and communications may increase the vaccination rates. Lessons learned from this study may give important insights on the implementation of a future HIV vaccine in adolescents, a group that will most likely be prioritized.
List of papers:
I. Viegas EO, Tembe N, Macovela E, Gonçalves E, Augusto O, Ismael N, Sitoe N, De Schacht C, Bhatt N, Meggi B, Araujo C, Sandström E, Biberfeld G, Nilsson C, Andersson S, Jani I, Osman N. Incidence of HIV and the prevalence of HIV, hepatitis B and syphilis among youths in Maputo, Mozambique : a cohort study. PLoS One;10(3): e0121452.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Viegas EO, Tembe N, Nilsson C, Meggi B, Maueia C, Augusto O, Stout R, Scarlatti G, Ferrari G, Earl PL, Wahren B, Andersson S, Robb ML, Osman N, Biberfeld G, Jani I, Sandström E and the TaMoVac study group. Intradermal HIV-1 DNA immunization using needle-free Zetajet™ injection followed by HIV-modified vaccinia virus Ankara vaccination is safe and highly immunogenic in Mozambican young adult s: a phase I randomized controlled trial. [Submitted]
III. Viegas EO, Augusto O, Ismael N, Kaliff M, Lillsunde-Larsson G, Ramqvist T, Nilsson C, Falk K, Osman N, Jani IV, Andersson S. Human papillomavirus prevalence and genotype distribution among young women and men in Maputo city, Mozambique. BMJ Open 2017;0:e015653.
Fulltext (DOI)
Pubmed
IV. Viegas EO, Ramgi P, Maiane J, Mahomed M, Guimarães A, Matsinhe G, Andersson S, Jani I, De Schacht C. Human papillomavirus vaccine coverage, awareness, knowledge and acceptance : a post-vaccination survey among parents and guardians of girls eligible for vaccination in the districts of Manica and Mocímboa da Praia, Mozambique. [Manuscript]
I. Viegas EO, Tembe N, Macovela E, Gonçalves E, Augusto O, Ismael N, Sitoe N, De Schacht C, Bhatt N, Meggi B, Araujo C, Sandström E, Biberfeld G, Nilsson C, Andersson S, Jani I, Osman N. Incidence of HIV and the prevalence of HIV, hepatitis B and syphilis among youths in Maputo, Mozambique : a cohort study. PLoS One;10(3): e0121452.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Viegas EO, Tembe N, Nilsson C, Meggi B, Maueia C, Augusto O, Stout R, Scarlatti G, Ferrari G, Earl PL, Wahren B, Andersson S, Robb ML, Osman N, Biberfeld G, Jani I, Sandström E and the TaMoVac study group. Intradermal HIV-1 DNA immunization using needle-free Zetajet™ injection followed by HIV-modified vaccinia virus Ankara vaccination is safe and highly immunogenic in Mozambican young adult s: a phase I randomized controlled trial. [Submitted]
III. Viegas EO, Augusto O, Ismael N, Kaliff M, Lillsunde-Larsson G, Ramqvist T, Nilsson C, Falk K, Osman N, Jani IV, Andersson S. Human papillomavirus prevalence and genotype distribution among young women and men in Maputo city, Mozambique. BMJ Open 2017;0:e015653.
Fulltext (DOI)
Pubmed
IV. Viegas EO, Ramgi P, Maiane J, Mahomed M, Guimarães A, Matsinhe G, Andersson S, Jani I, De Schacht C. Human papillomavirus vaccine coverage, awareness, knowledge and acceptance : a post-vaccination survey among parents and guardians of girls eligible for vaccination in the districts of Manica and Mocímboa da Praia, Mozambique. [Manuscript]
Institution: Karolinska Institutet
Supervisor: Nilsson, Charlotta
Co-supervisor: Andersson, Sören; Jani, Ilesh; Sandström, Eric
Issue date: 2017-09-08
Rights:
Publication year: 2017
ISBN: 978-91-7676-795-5
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