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1.  Afri-Can Forum 2 
Mukudu, Hillary | Martinson, Neil | Sartorius, Benn | Coetzee, Jenny | Dietrich, Janan | Mokgatswana, Kgaugelo | Jewkes, Rachel | Gray, Glenda E. | Dugas, Marylène | Béhanzin, Luc | Guédou, Fernand A. | Gagnon, Marie-Pierre | Alary, Michel | Rutakumwa, Rwamahe | Mbonye, Martin | Kiwanuka, Thadeus | Nakamanya, Sarah | Muhumuza, Richard | Nalukenge, Winfred | Seeley, Janet | Atujuna, Millicent | Wallace, Melissa | Brown, Ben | Bekker, Linda Gail | Newman, Peter A. | Harryparsad, Rushil | Olivier, Abraham J. | Jaspan, Heather B. | Wilson, Douglas | Dietrich, Janan | Martinson, Neil | Mukudu, Hillary | Mkhize, Nonhlanhla | Morris, Lynn | Cianci, Gianguido | Dinh, Minh | Hope, Thomas | Passmore, Jo-Ann S. | Gray, Clive M. | Henrick, Bethany M. | Yao, Xiao-Dan | Rosenthal, Kenneth L. | Henrick, Bethany M. | Yao, Xiao-Dan | Drannik, Anna G. | Abimiku, Alash’le | Rosenthal, Kenneth L. | Chanzu, Nadia | Mwanda, Walter | Oyugi, Julius | Anzala, Omu | Mbow, Moustapha | Jallow, Sabelle | Thiam, Moussa | Davis, Alberta | Diouf, Assane | Ndour, Cheikh T. | Seydi, Moussa | Dieye, Tandakha N. | Mboup, Souleymane | Goodier, Martin | Rilley, Eleanor | Jaye, Assan | Yao, Xiao-Dan | Omange, RW. | Henrick, Bethany M. | Lester, Richard T. | Kimani, Joshua | Ball, T. Blake | Plummer, Francis A. | Rosenthal, Kenneth L. | Béhanzin, Luc | Guédou, Fernand A. | Geraldo, Nassirou | Mastétsé, Ella Goma | Sossa, Jerôme Charles | Zannou, Marcel Djimon | Alary, Michel | Osawe, Sophia | Okpokoro, Evaezi | Okolo, Felicia | Umaru, Stephen | Abimiku, Rebecca | Audu, Sam | Datong, Pam | Abimiku, Alash’le | Nyange, Jacquelyn | Olenja, Joyce | Mutua, Gaudensia | Jaoko, Walter | Omosa-Manyonyi, Gloria | Farah, Bashir | Khaniri, Maureen | Anzala, Omu | Cockcroft, Anne | Tonkin, Kendra | Girish, Indu | Mhati, Puna | Cunningham, Ashley | Andersson, Neil | Farah, Bashir | Indangasi, Jackton | Jaoko, Walter | Mutua, Gaudensia | Khaniri, Maureen | Nyange, Jacquelyn | Anzala, Omu | Diphoko, Thabo | Gaseitsiwe, Simani | Maiswe, Victoria | Iketleng, Thato | Maruapula, Dorcas | Bedi, Keabetswe | Moyo, Sikhulile | Musonda, Rosemary | Wainberg, Mark | Makhema, Joseph | Novitsky, Vladimir | Marlink, Richard | Essex, Max | Okoboi, Stephen | Ssali, Livingstone | Kalibala, Sam | Birungi, Josephine | Egessa, Aggrey | Wangisi, Jonathan | Okullu, Lyavala Joanne | Bakanda, Celestin | Obare, Francis | Boer, I. Marion Sumari-de | Semvua, Hadija H. | van den Boogaard, Jossy | Kiwango, Krisanta W. | Ngowi, Kennedy M. | Nieuwkerk, Pythia T. | Aarnoutse, Rob E. | Kiwelu, Ireen | Muro, Eva | Kibiki, Gibson S. | Datiri, Ruth | Choji, Grace | Osawe, Sophia | Okpokoro, Evaezi | Okolo, Felicia | Umaru, Stephen | Abimiku, Rebecca | Audu, Samuel | Datong, Pam | Abimiku, Alash’le | Fomsgaard, A. | Karlsson, I. | Jensen, K. J. | Jensen, S. S. | Leo-Hansen, C. | Jespersen, S. | Da Silva Té, D. | Rodrigues, C. M. | da Silva, Z. J. | Janitzek, C. M. | Gerstoft, J. | Kronborg, G. | Okpokoro, Evaezi | Osawe, Sophia | Daitiri, Ruth | Choji, Grace | Umaru, Stephen | Okolo, Felicia | Datong, Pam | Abimiku, Alash’le | Emily, Nyariki | Joyce, Olenja | Robert, Lorway R. | Anzala, Anzala | Viljoen, Katie | Wendoh, Jerome | Kidzeru, Elvis | Karaoz, Ulas | Brodie, Eoin | Botha, Gerrit | Mulder, Nicola | Gray, Clive | Cameron, William | Stintzi, Alain | Jaspan, Heather | Levett, Paul N. | Alexander, David | Gulzar, Naveed | Grewal, Prabvir S. | Poon, Art F. Y. | Brumme, Zabrina | Harrigan, P. Richard | Brooks, James I. | Sandstrom, Paul A. | Calvez, Stryker | Sanche, Stephen E. | Scott, Jamie K. | Swartz, Leslie | Kagee, Ashraf | Lesch, Anthea | Kafaar, Zuhayr | De Wet, Anneliese | Okpokoro, Evaezi | Osawe, Sophia | Daitiri, Ruth | Choji, Grace | Umaru, Stephen | Okolo, Felicia | Datong, Pam | Abimiku, Alash’le | Dietrich, Janan | Smith, Tricia | Cotton, Laura | Hornschuh, Stefanie | van der Watt, Martin | Miller, Cari L. | Gray, Glenda | Smit, Jenni | Jaggernath, Manjeetha | Ndung’u, Thumbi | Brockman, Mark | Kaida, Angela | Akolo, Maureen | Kimani, Joshua | Gelmon, Larry | Chitwa, Michael | Osero, Justus | Cockcroft, Anne | Marokoane, Nobantu | Kgakole, Leagajang | Maswabi, Boikhutso | Mpofu, Neo | Ansari, Umaira | Andersson, Neil | Nakinobe, Elizabeth | Miiro, George Mukalazi | Zalwango, Flavia | Nakiyingi-Miiro, Jessica | Kaleebu, Potiano | Semwanga, John Ross | Nyanzi, Emily | Musoke, Saidat Namuli | Nakinobe, Elizabeth | Miiro, George | Mbidde, Edward Katongole | Lutalo, Tom | Kaleebu, Pontiano | Handema, Ray | Chianzu, Graham P. | Thiam, Moussa | Diagne-Gueye, Diabou | Ndiaye, Mame K. | Mbow, Moustapha | Ndiaye, Birahim P. | Traore, Ibrahima | Dia, Mamadou C. | Thomas, Gilleh | Tour-Kane, Coumba | Mboup, Souleymane | Jaye, Assan | Nyanzi, Emily | Mbidde, Edward Katongole | Kaleebu, Pontiano | Mpendo, Juliet | Kimani, Joshua | Birungi, Josephine | Muyindike, Winnie | Kambugu, Andrew | Sebastian, Hachizovu | Ray, Handema | Mike, Chaponda | Bertin, Kabuya Jean | Modest, Mulenga | Thiam, Moussa | Janha, Omar | Davis, Alberta | Amambua-Ngwa, Alfred | Nwakanma, Davis C. | Mboup, Souleymane | Jaye, Assan | Jespersen, Sanne | Hønge, Bo Langhoff | Esbjörnsson, Joakim | Medina, Candida | Da Silva TÉ, David | Correira, Faustino Gomes | Laursen, Alex Lund | Østergaard, Lars | Andersen, Andreas | Aaby, Peter | Erikstrup, Christian | Wejse, Christian | Dieye, Siry | Sarr, Moussa | Sy, Haby | Mbodj, Helene D. | Ndiaye, Marianne | Ndiaye, Amy | Moussa, Seydi | Jaye, Assan | Mboup, Souleymane | Nyombi, Balthazar M. | Shao, Elichilia R. | Chilumba, Innocent B. | Moyo, Sikhulile | Gaseitsiwe, Simani | Musonda, Rosemary | Datong, Pam | Inyang, Bucky | Osawe, Sophia | Izang, Abel | Cole, Chundung | Okolo, Felicia | Cameron, Bill | Rosenthal, Kenneth | Gray, Clive | Jaspan, Heather | Abimiku, Alash’le | Seraise, Boitumelo | Andrea-Marobela, Kerstin | Moyo, Sikhulile | Musonda, Rosemary | Makhema, Joseph | Essex, Max | Gaseitsiwe, Simani
BMC Infectious Diseases  2016;16(Suppl 2):315.
Table of contents
A1 Introduction to the 2nd synchronicity forum of GHRI/CHVI-funded Canadian and African HIV prevention and vaccine teams
O1 Voluntary medical male circumcision for prevention of heterosexual transmission of HIV in adult males in Soweto: What do indicators and incidence rate show?
Hillary Mukudu, Neil Martinson, Benn Sartorius
O2 Developing a peer-led community mobilization program for sex workers in Soweto: HIV risk and demographics
Jenny Coetzee, Janan Dietrich, Kgaugelo Mokgatswana, Rachel Jewkes, Glenda E. Gray
O3 Salient beliefs about adherence: A qualitative survey conducted as part of the demonstration study on "treatment as prevention" (TasP) and "pre-exposure prophylaxis" (PrEP) among female sex workers (FSWS) in Cotonou, Benin
Marylène Dugas, Luc Béhanzin, Fernand A. Guédou, Marie-Pierre Gagnon, Michel Alary
O4 Relative perception of risk as a driver of unsafe sexual practices among key populations: Cases of fisherfolk and women and their partners involved in multiple sexual partnerships in Uganda
Rwamahe Rutakumwa, Martin Mbonye, Thadeus Kiwanuka, Sarah Nakamanya, Richard Muhumuza, Winfred Nalukenge, Janet Seeley
O5 Exploring the acceptability of new biomedical HIV prevention technologies among MSM, adolescents and heterosexual adults in South Africa
Millicent Atujuna, Melissa Wallace, Ben Brown, Linda Gail Bekker, Peter A. Newman
O6 HIV-susceptible target cells in foreskins after voluntary medical male circumcision in South Africa
Rushil Harryparsad, Abraham J. Olivier, Heather B. Jaspan, Douglas Wilson, Janan Dietrich, Neil Martinson, Hillary Mukudu, Nonhlanhla Mkhize, Lynn Morris, Gianguido Cianci, Minh Dinh, Thomas Hope, Jo-Ann S. Passmore, Clive M. Gray
O7 HIV-1 proteins activate innate immune responses via TLR2 heterodimers
Bethany M. Henrick, Xiao-Dan Yao, Kenneth L. Rosenthal, the INFANT Study Team
O8 Characterization of an innate factor in human milk and mechanisms of action against HIV-1
Bethany M. Henrick, Xiao-Dan Yao, Anna G. Drannik, Alash’le Abimiku, Kenneth L. Rosenthal, the INFANT Study Team
O9 Secretor status and susceptibility to HIV infections among female sex workers in Nairobi, Kenya
Nadia Chanzu, Walter Mwanda, Julius Oyugi, Omu Anzala
O10 Natural Killer cell recall responsiveness to Gag-HIV-1 peptides of HIV-1 exposed but uninfected subjects are associated with peripheral CXCR6+ NK cell subsets
Moustapha Mbow, Sabelle Jallow, Moussa Thiam, Alberta Davis, Assane Diouf, Cheikh T. Ndour, Moussa Seydi, Tandakha N. Dieye, Souleymane Mboup, Martin Goodier, Eleanor Rilley, Assan Jaye
O11 Profiles of resistance: Local innate mucosal immunity to HIV-1 in commercial sex workers
Xiao-Dan Yao, RW. Omange, Bethany M. Henrick, Richard T. Lester, Joshua Kimani, T. Blake Ball, Francis A. Plummer, Kenneth L. Rosenthal
O12 Early antiretroviral therapy and pre-exposure prophylaxis for HIV prevention among female sex workers in Cotonou, Benin: A demonstration project
Luc Béhanzin, Fernand A. Guédou, Nassirou Geraldo, Ella Goma Mastétsé, Jerôme Charles Sossa, Marcel Djimon Zannou, Michel Alary
O13 Building capacity for HIV prevention trials: Preliminary data from a Nigerian cohort of HIV exposed sero-negatives (HESN)
Sophia Osawe, Evaezi Okpokoro, Felicia Okolo, Stephen Umaru, Rebecca Abimiku, Sam Audu, Pam Datong, Alash’le Abimiku
O14 Equipping healthcare professionals with skills required for the conduct of clinical trials in an effort to build capacity. Lessons learned
Jacquelyn Nyange, Joyce Olenja, Gaudensia Mutua, Walter Jaoko, Gloria Omosa-Manyonyi, Bashir Farah, Maureen Khaniri, Omu Anzala
O15 Educational technology to support active learning for HIV researchers and planners
Anne Cockcroft, Kendra Tonkin, Indu Girish, Puna Mhati, Ashley Cunningham, Neil Andersson
O16 From Lake Kivu (Rwanda) and Lake Malawi (Tanzania) to the shores of Lake Victoria (Uganda): Strengthening laboratory capacity through Good Clinical Laboratory Practice training
Bashir Farah, Jackton Indangasi, Walter Jaoko, Gaudensia Mutua, Maureen Khaniri, Jacquelyn Nyange, Omu Anzala
O17 Rilpivirine and etravirine resistance mutations in HIV-1 subtype C infected patients on a non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy in Botswana
Thabo Diphoko, Simani Gaseitsiwe, Victoria Maiswe, Thato Iketleng, Dorcas Maruapula, Keabetswe Bedi, Sikhulile Moyo, Rosemary Musonda, Mark Wainberg, Joseph Makhema, Vladimir Novitsky, Richard Marlink, Max Essex
O18 From home-based HIV testing to initiation of treatment: The AIDS Support Organization (TASO) Experience with Home-based HIV Counselling and Testing (HBHCT) among Adolescents in Uganda, 2005-2011
Stephen Okoboi, Livingstone Ssali, Sam Kalibala, Josephine Birungi, Aggrey Egessa, Jonathan Wangisi, Lyavala Joanne Okullu, Celestin Bakanda, Francis Obare41
O19 Feasibility study on using real time medication monitoring among HIV infected and Tuberculosis patients in Kilimanjaro, Tanzania
I. Marion Sumari-de Boer, Hadija H. Semvua, Jossy van den Boogaard, Krisanta W. Kiwango, Kennedy M. Ngowi, Pythia T. Nieuwkerk, Rob E. Aarnoutse, Ireen Kiwelu, Eva Muro, Gibson S. Kibiki
O20 Deaths still among sero-discordant cohort in Nigeria despite Access to treatment
Ruth Datiri, Grace Choji, Sophia Osawe, Evaezi Okpokoro, Felicia Okolo, Stephen Umaru, Rebecca Abimiku, Samuel Audu, Pam Datong, Alash’le Abimiku
O21 Therapeutic HIV-1 vaccine trials in Denmark and Guinea-Bissau
Fomsgaard A, Karlsson I, Jensen KJ, Jensen SS, Leo-Hansen C, Jespersen S, Da Silva Té D, Rodrigues CM, da Silva ZJ, Janitzek CM, Gerstoft J, Kronborg G, the WAPHIR Group
O22 Willingness to participate in a HIV vaccine Trial among HIV exposed sero-negative (HESN) persons in Jos, Nigeria
Evaezi Okpokoro, Sophia Osawe, Ruth Daitiri, Grace Choji, Stephen Umaru, Felicia Okolo, Pam Datong, Alash'le Abimiku
O23 Clinical research volunteers’ perceptions and experiences of screening for enrolment at KAVI-Institute of Clinical Research, Kenya
Nyariki Emily, Olenja Joyce, Lorway R. Robert, Anzala Anzala
O24 Gut microbiome, HIV-exposure, and vaccine responses in South African infants
Katie Viljoen, Jerome Wendoh, Elvis Kidzeru, Ulas Karaoz, Eoin Brodie, Gerrit Botha, Nicola Mulder, Clive Gray, William Cameron, Alain Stintzi, Heather Jaspan, for the INFANT study team
O25 Analysis of HIV pol diversity in the concentrated HIV epidemic in Saskatchewan
Paul N. Levett, David Alexander, Naveed Gulzar, Prabvir S. Grewal, Art F. Y. Poon, Zabrina Brumme, P. Richard Harrigan, James I. Brooks, Paul A. Sandstrom, Stryker Calvez, Stephen E. Sanche, Jamie K. Scott
P1 Evaluating a HIV vaccine research community engagement programme at two HIV prevention research centres in the Western Cape
Leslie Swartz, Ashraf Kagee, Anthea Lesch, Zuhayr Kafaar, Anneliese De Wet
P2 Validating HIV acquisition risk score using a cohort HIV exposed sero-negative persons in a discordant relationship in Jos, Nigeria, West Africa
Evaezi Okpokoro, Sophia Osawe, Ruth Daitiri, Grace Choji, Stephen Umaru, Felicia Okolo, Pam Datong, Alash'le Abimiku
P3 Bridging the gap between adults and adolescents and youth adults (AYA) – Employing a youth-centred approach to investigate HIV risk among AYA in Soweto and Durban, South Africa
Janan Dietrich, Tricia Smith, Laura Cotton, Stefanie Hornschuh, Martin van der Watt, Cari L. Miller, Glenda Gray, Jenni Smit, Manjeetha Jaggernath, Thumbi Ndung’u, Mark Brockman, Angela Kaida, on behalf of the AYAZAZI study teams
P4 Neighbours to sex workers: A key population that has been ignored
Maureen Akolo, Joshua Kimani, Prof Larry Gelmon, Michael Chitwa, Justus Osero
P5 Young women’s access to structural support programmes in a district of Botswana
Anne Cockcroft, Nobantu Marokoane, Leagajang Kgakole, Boikhutso Maswabi, Neo Mpofu, Umaira Ansari, Neil Andersson
P6 Voices for action from peri-urban Ugandan students, teachers and parents on HIV/STI prevention: Qualitative research results
Nakinobe Elizabeth, Miiro George Mukalazi, Zalwango Flavia, Nakiyingi-Miiro Jessica, Kaleebu Potiano
P7 Engaging Social Media as an education tool on the fly: The use of Facebook for HIV and Ebola prevention and awareness amongst adolescents in Uganda
John Ross Semwanga, Emily Nyanzi, Saidat Namuli Musoke, Elizabeth Nakinobe, George Miiro, Edward Katongole Mbidde, Tom Lutalo, Pontiano Kaleebu
P8 Circulating HIV-1 subtypes among sexual minority populations in Zambia
Ray Handema, Graham P. Chianzu
P9 The Development of HIV Bio-bank resource management to support clinical trial and Intervention research: WAPHIR experience
Moussa Thiam, Diabou Diagne-Gueye, Mame K. Ndiaye, Moustapha Mbow, Birahim P. Ndiaye, Ibrahima Traore, Mamadou C. Dia, Gilleh Thomas, Coumba Tour-Kane, Souleymane Mboup, Assan Jaye
P10 Capacity building for clinical trials as a novel approach for scaling up HIV prevention research initiatives in East Africa: achievements and challenges
Emily Nyanzi, Edward Katongole Mbidde, Pontiano Kaleebu, Juliet Mpendo, Joshua Kimani, Josephine Birungi, Winnie Muyindike, Andrew Kambugu
P11 Community and media perspective of research; an advocacy workshop on HIV prevention research
Hachizovu Sebastian, Handema Ray, Chaponda Mike, Kabuya Jean Bertin, Mulenga Modest
P12 Development of a quantitative HIV-1 and HIV-2 real time PCR (qRT-PCR) viral load assay
Moussa Thiam, Omar Janha, Alberta Davis, Alfred Amambua-Ngwa, Davis C. Nwakanma, Souleymane Mboup, Assan Jaye
P13 Differential effects of sex in a West African Cohort of HIV-1, HIV-2 and HIV-1/2 dual infected patients: Men are worse off
Sanne Jespersen, Bo Langhoff Hønge, Joakim Esbjörnsson, Candida Medina, David Da Silva TÉ, Faustino Gomes Correira, Alex Lund Laursen, Lars Østergaard, Andreas Andersen, Peter Aaby, Christian Erikstrup, Christian Wejse, for the Bissau HIV Cohort study group
P14 HIV-infected adolescents in transition from pediatric to adult HIV care in Dakar, Senegal: sample characteristics and immunological and virological profiles
Siry Dieye, Moussa Sarr, Haby Sy, Helene D Mbodj, Marianne Ndiaye, Amy Ndiaye, Seydi Moussa, Assan Jaye, Souleymane Mboup100
P15 Molecular characterization of vertically transmitted HIV-1 among children born to HIV-1 seropositive mothers in Northern Tanzania
Balthazar M. Nyombi, Elichilia R. Shao, Innocent B. Chilumba, Sikhulile Moyo, Simani Gaseitsiwe, Rosemary Musonda
P16 Breast-fed HIV-1 exposed infants play catch up. A preliminary report
Pam Datong, Bucky Inyang, Sophia Osawe, Abel Izang, Chundung Cole, Felicia Okolo, Bill Cameron, Kenneth Rosenthal, Clive Gray, Heather Jaspan, Alash’le Abimiku, the INFANT study team
P17 The frequency of N348I mutation in patient failing combination antiretroviral treatment In Botswana
Boitumelo Seraise, Kerstin Andrea-Marobela, Sikhulile Moyo, Rosemary Musonda, Joseph Makhema, Max Essex, Simani Gaseitsiwe
doi:10.1186/s12879-016-1466-6
PMCID: PMC4943497  PMID: 27410689
3.  Slow CD4+ T-Cell Recovery in Human Immunodeficiency Virus/Hepatitis B Virus-Coinfected Patients Initiating Truvada-Based Combination Antiretroviral Therapy in Botswana 
Open Forum Infectious Diseases  2016;3(3):ofw140.
Background. Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection has emerged as an important cause of morbidity and mortality. We determined the response to Truvada-based first-line combination antiretroviral therapy (cART) in HIV/HBV-coinfected verus HIV-monoinfected patients in Botswana.
Methods. Hepatitis B virus surface antigen (HBsAg), HBV e antigen (HBeAg), and HBV deoxyribonucleic acid (DNA) load were determined from baseline and follow-up visits in a longitudinal cART cohort of Truvada-based regimen. We assessed predictors of HBV serostatus and viral suppression (undetectable HBV DNA) using logistic regression techniques.
Results. Of 300 participants, 28 were HBsAg positive, giving an HIV/HBV prevalence of 9.3% (95% confidence interval [CI], 6.3–13.2), and 5 of these, 17.9% (95% CI, 6.1–36.9), were HBeAg positive. There was a reduced CD4+ T-cell gain in HIV/HBV-coinfected compared with HIV-monoinfected patients. Hepatitis B virus surface antigen and HBeAg loss was 38% and 60%, respectively, at 24 months post-cART initiation. The HBV DNA suppression rates increased with time on cART from 54% to 75% in 6 and 24 months, respectively.
Conclusions. Human immunodeficiency virus/HBV coinfection negatively affected immunologic recovery compared with HIV-1C monoinfection. Hepatitis B virus screening before cART initiation could help improve HBV/HIV treatment outcomes and help determine treatment options when there is a need to switch regimens.
doi:10.1093/ofid/ofw140
PMCID: PMC5084712  PMID: 27800524
Botswana; hepatitis B virus; HIV/HBV coinfection; tenofovir; Truvada
4.  Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization 
PLoS Pathogens  2016;12(7):e1005742.
The development of biomedical interventions to reduce acquisition of HIV-1 infection remains a global priority, however their potential effectiveness is challenged by very high HIV-1 envelope diversity. Two large prophylactic trials in high incidence, clade C epidemic regions in southern Africa are imminent; passive administration of the monoclonal antibody VRC01, and active immunization with a clade C modified RV144-like vaccines. We have created a large representative panel of C clade viruses to enable assessment of antibody responses to vaccines and natural infection in Southern Africa, and we investigated the genotypic and neutralization properties of recently transmitted clade C viruses to determine how viral diversity impacted antibody recognition. We further explore the implications of these findings for the potential effectiveness of these trials. A panel of 200 HIV-1 Envelope pseudoviruses was constructed from clade C viruses collected within the first 100 days following infection. Viruses collected pre-seroconversion were significantly more resistant to serum neutralization compared to post-seroconversion viruses (p = 0.001). Over 13 years of the study as the epidemic matured, HIV-1 diversified (p = 0.0009) and became more neutralization resistant to monoclonal antibodies VRC01, PG9 and 4E10. When tested at therapeutic levels (10ug/ml), VRC01 only neutralized 80% of viruses in the panel, although it did exhibit potent neutralization activity against sensitive viruses (IC50 titres of 0.42 μg/ml). The Gp120 amino acid similarity between the clade C panel and candidate C-clade vaccine protein boosts (Ce1086 and TV1) was 77%, which is 8% more distant than between CRF01_AE viruses and the RV144 CRF01_AE immunogen. Furthermore, two vaccine signature sites, K169 in V2 and I307 in V3, associated with reduced infection risk in RV144, occurred less frequently in clade C panel viruses than in CRF01_AE viruses from Thailand. Increased resistance of pre-seroconversion viruses and evidence of antigenic drift highlights the value of using panels of very recently transmitted viruses and suggests that interventions may need to be modified over time to track the changing epidemic. Furthermore, high divergence such as that observed in the older clade C epidemic in southern Africa may impact vaccine efficacy, although the correlates of infection risk are yet to be defined in the clade C setting. Findings from this study of acute/early clade C viruses will aid vaccine development, and enable identification of new broad and potent antibodies to combat the HIV-1 C-clade epidemic in southern Africa.
Author Summary
Vaccine and passive immunization prophylactic trials that rely on antibody-mediated protection are planned for HIV-1 clade C epidemic regions of southern Africa, which have amongst the highest HIV-1 incidences globally. This includes a phase 2b trial of passively administered monoclonal antibody, VRC01; as well as a phase 3 trial using the clade C modified version of the partially efficacious RV144 vaccine. The extraordinary diversity of HIV-1 poses a major obstacle to these interventions, and our study aimed to determine the implications of viral diversity on antibody recognition. Investigations using our panel of very early viruses augment current knowledge of vulnerable targets on transmitted viruses for vaccine design and passive immunization studies. Evidence of antigenic drift with viruses becoming more resistant over time suggests that these prevention modalities will need to be updated over time and that combinations of antibodies will be necessary to achieve coverage in passive immunization studies. We further show that it may be more difficult to obtain protection in the genetically diverse clade C epidemic compared to RV144 where the epidemic is less diverse, although it should be noted that the correlates of infection risk are yet to be defined in the clade C setting.
doi:10.1371/journal.ppat.1005742
PMCID: PMC4951126  PMID: 27434311
5.  Plasma Cytokine Levels and Risk of HIV Type 1 (HIV-1) Transmission and Acquisition: A Nested Case-Control Study Among HIV-1–Serodiscordant Couples 
The Journal of Infectious Diseases  2014;211(9):1451-1460.
Background. A heightened proinflammatory state has been hypothesized to enhance human immunodeficiency virus type 1 (HIV-1) transmission – both susceptibility of HIV-1-exposed persons and infectiousness of HIV-1-infected persons.
Methods. Using prospective data from heterosexual African couples with HIV-1 serodiscordance, we conducted a nested case-control analysis to assess the relationship between cytokine concentrations and the risk of HIV-1 acquisition. Case couples (n = 120) were initially serodiscordant couples in which HIV-1 was transmitted to the seronegative partner during the study; control couples (n = 321) were serodiscordant couples in which HIV-1 was not transmitted to the seronegative partner. Differences in a panel of 30 cytokines were measured using plasma specimens from both HIV-1–susceptible and HIV-1–infected partners. Plasma was collected before seroconversion for cases.
Results. For both HIV-1–infected and HIV-1–susceptible partners, cases and controls had significantly different mean responses in cytokine panels (P < .001, by the Hotelling T2 test), suggesting a broadly different pattern of immune activation for couples in which HIV-1 was transmitted, compared with couples without transmission. Individually, log10 mean concentrations of interleukin 10 (IL-10) and CXCL10 were significantly higher for both HIV-1–susceptible and HIV-1–infected case partners, compared with HIV-1–susceptible and HIV-1–infected control partners (P < .01 for all comparisons). In multivariate analysis, HIV-1 transmission was significantly associated with elevated CXCL10 concentrations in HIV-1–susceptible partners (P = .001) and with elevated IL-10 concentrations in HIV-1–infected partners (P = .02).
Conclusions. Immune activation, as measured by levels of cytokine markers, particularly elevated levels of IL-10 and CXCL1, are associated with increased HIV-1 susceptibility and infectiousness.
doi:10.1093/infdis/jiu621
PMCID: PMC4447828  PMID: 25389306
HIV-1 acquisition; immune activation; Africa
6.  Establishing and Delivering Quality Radiation Therapy in Resource-Constrained Settings: The Story of Botswana 
Journal of Clinical Oncology  2015;34(1):27-35.
There is a global cancer crisis, and it is disproportionately affecting resource-constrained settings, especially in low- and middle-income countries (LMICs). Radiotherapy is a critical and cost-effective component of a comprehensive cancer control plan that offers the potential for cure, control, and palliation of disease in greater than 50% of patients with cancer. Globally, LMICs do not have adequate access to quality radiation therapy and this gap is particularly pronounced in sub-Saharan Africa. Although there are numerous challenges in implementing a radiation therapy program in a low-resource setting, providing more equitable global access to radiotherapy is a responsibility and investment worth prioritizing. We outline a systems approach and a series of key questions to direct strategy toward establishing quality radiation services in LMICs, and highlight the story of private-public investment in Botswana from the late 1990s to the present. After assessing the need and defining the value of radiation, we explore core investments required, barriers that need to be overcome, and assets that can be leveraged to establish a radiation program. Considerations addressed include infrastructure; machine choice; quality assurance and patient safety; acquisition, development, and retention of human capital; governmental engagement; public–private partnerships; international collaborations; and the need to critically evaluate the program to foster further growth and sustainability.
doi:10.1200/JCO.2015.62.8412
PMCID: PMC5070566  PMID: 26578607
7.  Recruitment, Follow-Up and Characteristics of HIV Infected Adults who Use Illicit Drugs in Southern Africa 
Journal of drug abuse  2015;1(1):7.
Background
With one of the worst HIV prevalence rates in the world, Botswana has made great strides in addressing AIDS. Nevertheless, to fully contain the epidemic, outreach to marginalized groups, including illicit drug users, is critical.
Objective
To conduct targeted outreach within an intervention trial to recruit HIV-infected drug users and assess HIV disease and nutritional status.
Method
Recruitment strategies included safeguarding confidentiality, involving ocal health-care professionals, advertising, and participation incentives. Urine toxicology, CD4 cell count, HIV viral load, blood chemistry, plasma micronutrients, dietary history, drug use and morbidity were assessed for two years.
Results
Targeted outreach identified 138 HIV-infected persons who used marijuana; 18.1% had CD4 cell counts ≤ 350 cells/μL and 39.9% had low BMI. Eligible marijuana users (N=52) had significantly lower BMI (21.8 3.7 vs. 24.3 ± 5.3 kg/m2, P=0.001), higher HIV viral load (4.36 ± 0.89 vs. 4.09 ± 0.89 log10, P=0.018), and higher kilocalorie intake (1924 ± 1055 vs. 1620 ± 926 Kcalories, P=0.025) than those who did not use marijuana (N=748) with similar CD4 cell count. Marijuana users ≥ 40 years old had more opportunistic diseases (P=0.020) than non-users of the same age. Benzodiazepine use was detected among 57 participants and they had higher BMI than marijuana users (24.4 ± 6.8 vs. 21.8 ± 3.7 kg/m2, P= 0.017).
Conclusion
A population stigmatized by illicit drug use and HIV-infection can be brought into a clinical research setting in Africa. HIV-infected marijuana users were at a risk for higher HIV viral load, lower BMI and more comorbidities than nonusers. Outreach to this marginalized group is important for containing the HIV epidemic.
PMCID: PMC4739794  PMID: 26855969
Marijuana; Benzodiazepines; Botswana; HIV; Recruitment; Nutritional status; HIV disease progression
8.  Long-Range HIV Genotyping Using Viral RNA and Proviral DNA for Analysis of HIV Drug Resistance and HIV Clustering 
Journal of Clinical Microbiology  2015;53(8):2581-2592.
The goal of the study was to improve the methodology of HIV genotyping for analysis of HIV drug resistance and HIV clustering. Using the protocol of Gall et al. (A. Gall, B. Ferns, C. Morris, S. Watson, M. Cotten, M. Robinson, N. Berry, D. Pillay, and P. Kellam, J Clin Microbiol 50:3838–3844, 2012, doi:10.1128/JCM.01516-12), we developed a robust methodology for amplification of two large fragments of viral genome covering about 80% of the unique HIV-1 genome sequence. Importantly, this method can be applied to both viral RNA and proviral DNA amplification templates, allowing genotyping in HIV-infected subjects with suppressed viral loads (e.g., subjects on antiretroviral therapy [ART]). The two amplicons cover critical regions across the HIV-1 genome (including pol and env), allowing analysis of mutations associated with resistance to protease inhibitors, reverse transcriptase inhibitors (nucleoside reverse transcriptase inhibitors [NRTIs] and nonnucleoside reverse transcriptase inhibitors [NNRTIs]), integrase strand transfer inhibitors, and virus entry inhibitors. The two amplicons generated span 7,124 bp, providing substantial sequence length and numbers of informative sites for comprehensive phylogenic analysis and greater refinement of viral linkage analyses in HIV prevention studies. The long-range HIV genotyping from proviral DNA was successful in about 90% of 212 targeted blood specimens collected in a cohort where the majority of patients had suppressed viral loads, including 65% of patients with undetectable levels of HIV-1 RNA loads. The generated amplicons could be sequenced by different methods, such as population Sanger sequencing, single-genome sequencing, or next-generation ultradeep sequencing. The developed method is cost-effective—the cost of the long-range HIV genotyping is under $140 per subject (by Sanger sequencing)—and has the potential to enable the scale up of public health HIV prevention interventions.
doi:10.1128/JCM.00756-15
PMCID: PMC4508442  PMID: 26041893
9.  Unintended pregnancy, contraceptive use, and childbearing desires among HIV-infected and HIV-uninfected women in Botswana: across-sectional study 
BMC Public Health  2016;16:44.
Background
Little is known about the impact of knowledge of HIV serostatus on pregnancy intention and contraceptive use in high-HIV-burden southern African settings in the era of widespread antiretroviral treatment availability.
Methods
We analyzed interview data collected among 473 HIV-uninfected and 468 HIV-infected pregnant and recently postpartum women at two sites in southern Botswana. Participants were interviewed about their knowledge of their HIV status prior to pregnancy, intendedness of the pregnancy, contraceptive use, and future childbearing desires.
Results
The median age of the 941 women was 27 years, median lifetime pregnancies was 2, and 416 (44 %) of pregnancies were unintended. Among women reporting unintended pregnancy, 36 % were not using a contraceptive method prior to conception. Among contraception users, 81 % used condoms, 13 % oral contraceptives and 5 % an injectable contraceptive. In univariable analysis, women with unintended pregnancy had a higher number of previous pregnancies (P = <0.0001), were less educated (P = 0.0002), and less likely to be married or living with a partner (P < 0.0001). Thirty-percent reported knowing that they were HIV-infected, 48 % reported knowing they were HIV-uninfected, and 22 % reported not knowing their HIV status prior to conception. In multivariable analysis, women who did not know their HIV status pre-conception were more likely to report their pregnancy as unintended compared to women who knew that they were HIV-uninfected (aOR = 1.7; 95%CI: 1.2-2.5). After controlling for other factors, unintended pregnancy was not associated with knowing one’s HIV positive status prior to conception (compared with knowing one’s negative HIV status prior to conception). Among women with unintended pregnancy, there was no association between knowing their HIV status and contraceptive use prior to pregnancy in adjusted analyses. Sixty-one percent of women reported not wanting any more children after this pregnancy, with HIV-infected women significantly more likely to report not wanting any more children compared to HIV-uninfected women (aOR = 3.9; 95%CI: 2.6-5.8).
Conclusions
The high rates of reported unintended pregnancy and contraceptive failure/misuse underscore an urgent need for better access to effective contraceptive methods for HIV-uninfected and HIV -infected women in Botswana. Lower socioeconomic status and lack of pre-conception HIV testing may indicate higher risk for unintended pregnancy in this setting.
doi:10.1186/s12889-015-2498-3
PMCID: PMC4715872  PMID: 26774918
Unintended pregnancy; Contraception; Family planning; HIV; Africa; Botswana; Tshipidi
10.  Vitamin D Insufficiency in HIV-Infected Pregnant Women Receiving Antiretroviral Therapy is not associated with Morbidity, Mortality or Growth Impairment in Their Uninfected Infants in Botswana 
Background
Low maternal 25(OH)D (vitamin D) values have been associated with higher mortality and impaired growth among HIV-exposed uninfected (HEU) infants of antiretroviral (ART)-naïve women. These associations have not been studied among HEU infants of women receiving ART.
Methods
We performed a nested case-control study in the Botswana Mma Bana Study, a study providing ART to women during pregnancy and breastfeeding. Median maternal vitamin D values, and the proportion with maternal vitamin D insufficiency, were compared between women whose HEU infants experienced morbidity/mortality during 24 months of follow-up and women with non-hospitalized HEU infants. Growth faltering was assessed for never hospitalized infants attending the 24-month-of-life visit. Multivariate logistic regression models determined associations between maternal vitamin D insufficiency and infant morbidity/mortality and growth faltering.
Results
Delivery plasma was available and vitamin D levels assayable from 119 (86%) of 139 cases and 233 (84%) of 278 controls, and did not differ significantly between cases and controls (median 36.7 ng/mL; IQR 29.1- 44.7 vs. 37.1 ng/mL; IQR 30.0 - 47.2; p = 0.32). Vitamin D insufficiency (< 32 ng/mL) was recorded among 112 (31.8%) of 352 women at delivery and occurred most frequently among women delivering in winter. Multivariate logistic regression models adjusted for maternal HIV disease progression did not show associations between maternal vitamin D insufficiency at delivery and child morbidity/mortality, or 24-month-of-life growth faltering.
Conclusions
Vitamin D insufficiency was common among ART treated pregnant women in Botswana, but was not associated with morbidity, mortality or growth impairment in their HIV-uninfected children.
doi:10.1097/INF.0000000000000428
PMCID: PMC4216630  PMID: 25037041
HIV-exposed uninfected infants; maternal vitamin D; morbidity; mortality; growth
11.  Molecular characterisation of hepatitis B virus in HIV-1 subtype C infected patients in Botswana 
BMC Infectious Diseases  2015;15:335.
Background
Hepatitis B virus (HBV) is a major global health problem especially in sub-Saharan Africa and in East Asia. Ten hepatitis B virus genotypes have been described that differ by geographic distribution, disease progression, and response to treatment. Escape mutations within the surface open reading frame (ORF) affect HBV antigenicity leading to failures in diagnosis, vaccine and hepatitis B immunoglobulin therapy. However, the molecular characteristics of HBV in Botswana, a highly endemic country, are unknown. We describe the molecular characteristics of HBV and prevalence of escape mutants among HIV/HBV coinfected individuals Botswana.
Methods
DNA was extracted from archived plasma samples from 81 HIV/HBV co-infected participants from various clinical studies at the Botswana Harvard AIDS Institute Partnership. A 415 base pair (bp) fragment of the polymerase gene was amplified by semi-nested PCR. In a subset of samples, a 2100 bp fragment was amplified. The PCR product was genotyped using Big Dye sequencing chemistry and the sequences were analysed for genotypes and mutations.
Results
Of the 81 samples included, 70 (86 %) samples were successfully genotyped. Genotype A was found in 56 (80 %) participants, D in 13 (18.6 %), and 1 (1.4 %) was genotype E. Escape mutations previously linked with failure of diagnosis or escaping active vaccination and passive immunoglobulin therapy were detected in 12 (17.1 %) participants at positions 100, 119, 122, 123, 124, 126, 129, 130, 133, 134 and 140 of the S ORF. Genotypes and escape mutations were not significantly associated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AST platelet ratio index (APRI).
Conclusion
Genotypes A, D and E were found in this cohort of HIV coinfected patients in Botswana, consistent with the findings from the sub-Saharan Africa region. Some escape mutations which have previously been associated with diagnosis failure, escaping vaccine and immunoglobulin therapy were also observed and are important in guiding future policies related to vaccine implementation, therapeutic guidelines, and diagnostic guidelines. They are also important for identifying patients who are at an increased risk of disease progression and to choose optimal therapy. Future research should focus on determining the clinical significance of the different HBV genotypes and mutations found in this population.
doi:10.1186/s12879-015-1096-4
PMCID: PMC4535680  PMID: 26268355
12.  Estimated age and gender profile of individuals missed by a home-based HIV testing and counselling campaign in a Botswana community 
Introduction
It would be useful to understand which populations are not reached by home-based HIV-1 testing and counselling (HTC) to improve strategies aimed at linking these individuals to care and reducing rates of onward HIV transmission.
Methods
We present the results of a baseline home-based HTC (HBHTC) campaign aimed at counselling and testing residents aged 16 to 64 for HIV in the north-eastern sector of Mochudi, a community in Botswana with about 44,000 inhabitants. Collected data were compared with population references for Botswana, the United Nations (UN) estimates based on the National Census data and the Botswana AIDS Impact Survey IV (BAIS-IV). Analyzed data and references were stratified by age and gender.
Results
A total of 6238 age-eligible residents were tested for HIV-1; 1247 (20.0%; 95% CI 19.0 to 21.0%) were found to be HIV positive (23.7% of women vs. 13.4% of men). HIV-1 prevalence peaked at 44% in 35- to 39-year-old women and 32% in 40- to 44-year-old men. A lower HIV prevalence rate, 10.9% (95% CI 9.5 to 12.5%), was found among individuals tested for the first time. A significant gender gap was evident in all analyzed subsets. The existing HIV transmission network was analyzed by combining phylogenetic mapping and household structure. Between 62.4 and 71.8% of all HIV-positive individuals had detectable virus. When compared with the UN and BAIS-IV estimates, the proportion of men missed by the testing campaign (48.5%; 95% CI 47.0 to 50.0%) was significantly higher than the proportion of missed women (14.2%; 95% CI 13.2 to 15.3%; p<0.0001). The estimated proportion of missed men peaked at about 60% in the age group 30 to 39 years old. The proportions of missed women were substantially smaller, at approximately 28% within the age groups 30 to 34 and 45 to 49 years old.
Conclusions
The HBHTC campaign seems to be an efficient tool for reaching individuals who have never been tested previously in southern African communities. However, about half of men from 16 to 64 years old were not reached by the HBHTC, including about 60% of men between 30 and 40 years old. Alternative HTC strategies should be developed to bring these men to care, which will contribute to reduction of HIV incidence in communities.
doi:10.7448/IAS.18.1.19918
PMCID: PMC4450241  PMID: 26028155
HIV-1; home-based HTC; Botswana; gender; age; missing individuals; individuals tested for the first time
13.  Single-Arm Evaluation of the AccuCirc Device for Early Infant Male Circumcision in Botswana 
Existing devices for early infant male circumcision (EIMC) have inherent limitations. We evaluated the newly developed AccuCirc device by circumcising 151 clinically well, full-term male infants with birth-weight ≥ 2.5 kg within the first 10 days of life from a convenience sample in two hospitals in Botswana. No major adverse events were observed. There was one local infection, five cases of minor bleeding and one case of moderate bleeding. In three cases the device made only partial incisions that were completed immediately by the provider without complications. Parental satisfaction was high: > 96% of mothers stated they would circumcise a future son. The pre-assembled, sterile AccuCirc kit has the potential to overcome obstacles related to supply chain management and on-site instrument disinfection that can pose challenges in resource-limited settings. In our study the AccuCirc was safe and it should be considered for programmatic EIMC in resource-limited settings.
doi:10.1097/QAI.0000000000000136
PMCID: PMC4041082  PMID: 24594500
14.  Effect of Micronutrient Supplementation on Disease Progression in Asymptomatic, Antiretroviral-Naive, HIV-Infected Adults in Botswana A Randomized Clinical Trial 
JAMA  2013;310(20):2154-2163.
IMPORTANCE
Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive.
OBJECTIVE
To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive.
DESIGN, SETTING, AND PARTICIPANTS
Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), seleniumalone, or multivitamins with selenium vs placebo inafactorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009.
INTERVENTIONS
Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo.
MAIN OUTCOMES AND MEASURES
Reaching a CD4 cell count less than 200/μL until May 2008; after this date, reaching a CD4 cell count of 250/μL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study.
RESULTS
There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of combined outcomes for disease progression (CD4 cell count ≤250/μL, AIDS-defining conditions, or AIDS-related death, whichever occurred earlier [adjusted HR, 0.56; 95% CI, 0.33-0.95; P = .03; AER, 6.48/100 person-years; censoring rate, 0.90; 23 events]). There was no effect of supplementation on HIV viral load. Multivitamins alone and selenium supplementation alone were not statistically different from placebo for any end point. Reported adverse events were adjudicated as unlikely to be related to the intervention, and there were no notable differences in incidence of HIV-related and health-related events among study groups.
CONCLUSIONS AND RELEVANCE
In ART-naive HIV-infected adults, 24-month supplementation with a single supplement containing multivitamins and selenium was safe and significantly
doi:10.1001/jama.2013.280923
PMCID: PMC4347896  PMID: 24281460
15.  Evaluation of the False Recent Classification Rates of Multiassay Algorithms in Estimating HIV Type 1 Subtype C Incidence 
Abstract
Laboratory cross-sectional assays are useful for the estimation of HIV incidence, but are known to misclassify individuals with long-standing infection as recently infected. The false recent rate (FRR) varies widely across geographic areas; therefore, accurate estimates of HIV incidence require a locally defined FRR. We determined FRR for Botswana, where HIV-1 subtype C infection is predominant, using the BED capture enzyme immunoassay (BED), a Bio-Rad Avidity Index (BAI) assay (a modification of the Bio-Rad HIV1/2+O EIA), and two multiassay algorithms (MAA) that included clinical data. To estimate FRR, stored blood samples from 512 antiretroviral (ARV)-naive HIV-1 subtype C-infected individuals from a prospective cohort in Botswana were tested at 18–24 months postenrollment. The following FRR mean (95% CI) values were obtained: BED 6.05% (4.15–8.48), BAI 5.57% (3.70–8.0), BED-BAI 2.25% (1.13–4.0), and a combination of BED-BAI with CD4 (>200) and viral load (>400) threshold 1.43% (0.58–2.93). The interassay agreement between BED and BAI was 92.8% (95% CI, 90.1–94.5) for recent/long-term classification. Misclassification was associated with viral suppression for BED [adjusted OR (aOR) 10.31; p=0.008], BAI [aOR 9.72; p=0.019], and MAA1 [aOR 16.6; p=0.006]. Employing MAA can reduce FRR to <2%. A local FRR can improve cross-sectional HIV incidence estimates.
doi:10.1089/aid.2013.0055
PMCID: PMC3887420  PMID: 23937344
16.  Undisclosed Antiretroviral Drug Use in a Multinational Clinical Trial (HIV Prevention Trials Network 052) 
The Journal of Infectious Diseases  2013;208(10):1624-1628.
The HIV Prevention Trials Network 052 study enrolled serodiscordant couples. Index participants infected with human immunodeficiency virus reported no prior antiretroviral (ARV) treatment at enrollment. ARV drug testing was performed retrospectively using enrollment samples from a subset of index participants. ARV drugs were detected in 45 of 96 participants (46.9%) with an undetectable viral load, 2 of 48 (4.2%) with a low viral load, and 1 of 65 (1.5%) with a high viral load (P < .0001); they were also detected in follow-up samples from participants who were not receiving study-administered treatment. ARV drug testing may be useful in addition to self-report of ARV drug use in some clinical trial settings.
doi:10.1093/infdis/jit390
PMCID: PMC3805242  PMID: 23908493
HIV; antiretroviral drug; self-report; HPTN 052; Africa; clinical trial
17.  Daily Acyclovir to Decrease Herpes Simplex Virus Type 2 (HSV-2) Transmission from HSV-2/HIV-1 Coinfected Persons: A Randomized Controlled Trial 
The Journal of Infectious Diseases  2013;208(9):1366-1374.
Background. Daily suppressive therapy with valacyclovir reduces risk of sexual transmission of herpes simplex virus type 2 (HSV-2) in HSV-2–serodiscordant heterosexual couples by 48%. Whether suppressive therapy reduces HSV-2 transmission from persons coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) is unknown.
Methods. Within a randomized trial of daily acyclovir 400 mg twice daily in African HIV-1 serodiscordant couples, in which the HIV-1–infected partner was HSV-2 seropositive, we identified partnerships in which HIV-1–susceptible partners were HSV-2 seronegative to estimate the effect of acyclovir on risk of HSV-2 transmission.
Results. We randomly assigned 911 HSV-2/HIV-1–serodiscordant couples to daily receipt of acyclovir or placebo. We observed 68 HSV-2 seroconversions, 40 and 28 in acyclovir and placebo groups, respectively (HSV-2 incidence, 5.1 cases per 100 person-years; hazard ratio [HR], 1.35 [95% confidence interval, .83–2.20]; P = .22). Among HSV-2–susceptible women, vaginal drying practices (adjusted HR, 44.35; P = .004) and unprotected sex (adjusted HR, 9.91; P = .002) were significant risk factors for HSV-2 acquisition; having more children was protective (adjusted HR, 0.47 per additional child; P = .012). Among HSV-2–susceptible men, only age ≤30 years was associated with increased risk of HSV-2 acquisition (P = .016).
Conclusions. Treatment of African HSV-2/HIV-1–infected persons with daily suppressive acyclovir did not decrease risk of HSV-2 transmission to susceptible partners. More-effective prevention strategies to reduce HSV-2 transmission from HIV-1–infected persons are needed.
doi:10.1093/infdis/jit333
PMCID: PMC3789565  PMID: 23901094
HSV-2; HIV-1; acyclovir; transmission; serodiscordant couples; Africa
18.  Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial 
The Lancet. Infectious diseases  2014;14(4):281-290.
Summary
Background
Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes.
Methods
The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratified by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00074581.
Findings
1763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group after randomisation). Median CD4 counts at randomisation were 442 (IQR 373–522) cells per μL in patients assigned to the early treatment group and 428 (357–522) cells per μL in those allocated delayed antiretroviral treatment. In the delayed group, antiretroviral treatment was initiated at a median CD4 count of 230 (IQR 197–249) cells per μL. Primary clinical events were reported in 57 individuals assigned to early treatment initiation versus 77 people allocated to delayed antiretroviral treatment (hazard ratio 0·73, 95% CI 0·52–1·03; p=0·074). New-onset AIDS events were recorded in 40 participants assigned to early antiretroviral treatment versus 61 allocated delayed initiation (0·64, 0·43–0·96; p=0·031), tuberculosis developed in 17 versus 34 patients, respectively (0·49, 0·28–0·89, p=0·018), and primary non-AIDS events were rare (12 in the early group vs nine with delayed treatment). In total, 498 primary and secondary outcomes occurred in the early treatment group (incidence 24·9 per 100 person-years, 95% CI 22·5–27·5) versus 585 in the delayed treatment group (29·2 per 100 person-years, 26·5–32·1; p=0·025). 26 people died, 11 who were allocated to early antiretroviral treatment and 15 who were assigned to the delayed treatment group.
Interpretation
Early initiation of antiretroviral treatment delayed the time to AIDS events and decreased the incidence of primary and secondary outcomes. The clinical benefits recorded, combined with the striking reduction in HIV-1 transmission risk previously reported, provides strong support for earlier initiation of antiretroviral treatment.
Funding
US National Institute of Allergy and Infectious Diseases.
doi:10.1016/S1473-3099(13)70692-3
PMCID: PMC4144040  PMID: 24602844
19.  No Clinically Significant Drug Resistance Mutations In HIV-1 subtype C Infected Women After Discontinuation Of NRTI-Based Or PI-Based HAART For PMTCT In Botswana 
Risk of developing drug resistance after stopping antiretroviral regimens to prevent mother-to-child HIV-1 transmission (PMTCT) is unknown. Mma Bana Study randomized treatment-naïve pregnant women with CD4 ≥200 cells/mm3 to receive either abacavir/zidovudine/lamivudine (triple NRTI arm) or lopinavir/ritonavir/zidovudine/lamivudine (PI arm). Drugs were discontinued after 6 months breastfeeding. One month post-discontinuation, 29 NRTI arm samples and 25 PI arm samples were successfully genotyped. No clinically significant antiretroviral resistance mutations were detected. Eight minor resistance mutations were found among 11(20%) women (3 from NRTI arm, 8 from PI arm), occurring at similar frequencies to those reported in HIV-1 subtype C treatment naive cohorts.
doi:10.1097/QAI.0b013e31829308f8
PMCID: PMC3762949  PMID: 23542639
Mother-to-Child HIV transmission; Highly Active Antiretroviral Therapy; Minor drug resistance mutations; Botswana
20.  HIV transmission and 24-month survival in a randomized trial of HAART to prevent MTCT during pregnancy and breastfeeding in Botswana (The Mma Bana Study) 
AIDS (London, England)  2013;27(12):1911-1920.
Objectives
Highly active antiretroviral therapy (HAART) for prevention of mother-to-child HIV transmission (MTCT) may impact long-term survival of mothers and children.
Design
Randomized clinical trial.
Methods
HIV–infected pregnant women with CD4 ≥200 cells/mm3 were randomly assigned to abacavir, zidovudine, lamivudine (Arm A) or lopinavir–ritonavir, zidovudine–lamivudine (Arm B) from week 26–34 gestation through planned weaning by 6 months postpartum. Women with baseline CD4 <200 received nevirapine–zidovudine–lamivudine indefinitely (Obs arm), as did randomized women later qualifying for treatment.
Results
Among 560 randomized and 170 observational women enrolled, there were 14 deaths (1.9%); 1 antenatally (Obs), 3 from delivery though 6 months postpartum (1 Arm A, 2 Obs), and 10 from 6–24 months postpartum (5 Arm A, 3 Arm B, 2 Obs). Time to death or CD4 <200 was shorter in Arm A vs. B (p=0.03). Of 709 live-born children, 97% breastfed for median 5.8 months. Of 37 (5.2%) deaths by 24 months, 9 were before breastfeeding initiated (3 Arm A, 2 Arm B, 4 Obs); 6 while breastfeeding (1 Arm A, 2 Arm B, 3 Obs); and 22 after weaning (9 Arm A, 11 Arm B, 2 Obs). Only 8 children (1.1%) were HIV-infected at 24 months (6 Arm A, 1 Arm B, 1 Obs), all before 6 months.
Conclusions
Low MTCT was maintained through extended follow-up in all arms. Disease progression appeared slower after discontinuing protease inhibitor-based HAART, but a concerning number of maternal deaths occurred after stopping either regimen. Strategies to improve maternal and child survival in the post-intervention period are required.
PMCID: PMC3987116  PMID: 24180000
HIV; MTCT; Botswana; Africa; Antiretrovirals; Infant Survival; Maternal Health
21.  Persistently Elevated Serum Interleukin-6 Predicts Mortality Among Adults Receiving Combination Antiretroviral Therapy in Botswana: Results from a Clinical Trial 
Abstract
Elevated serum levels of inflammatory biomarkers have been associated with increased mortality and morbidity among HIV-infected individuals receiving combination antiretroviral therapy (cART) in European and U.S. cohorts. Few similar data are available from sub-Saharan Africa, where most cART-treated adults reside and the prevalence of advanced immunosuppression and opportunistic infections (OIs) at cART initiation is higher. This was a retrospective nested case-control analysis of clinical trial data from the completed Adult Antiretroviral Treatment and Drug Resistance (“Tshepo”) study, 2002–2007, Gaborone, Botswana. We measured pretreatment serum levels of interleukin-6 (IL-6), high sensitivity C-reactive protein, and D-dimer in stored plasma samples from 32 deceased participants (cases) and 64 survivors (controls), matched for age, sex, baseline CD4+ cell count, and plasma HIV-1 RNA. Multivariate conditional logistic regression analyses were used to compare inflammatory biomarker levels, adjusting for pretreatment body mass index (BMI) and the presence of OIs. A total of 37 (5.7%) of 650 patients died on study, for a crude mortality rate of 20.6/1,000 person-years. Of 37 (86%) study participants who died on study 32 were included in this analysis. Causes of death (n=32) included non-AIDS-defining events (31.3%), HIV-related OIs (28.1%), cART/toxicity-related (21.9%), other infectious etiologies (15.6%), and unknown (3.1%). Median time to death was 31 weeks [interquartile range (IQR) 14–64]. Median baseline levels of all three biomarkers were higher in cases compared to matched controls. After adjusting for BMI and the presence of OIs, only baseline and most recent (near time of event) levels of IL-6 remained as significant predictors of all-cause mortality [adjusted OR (aOR)=1.25, 95% CI (1.05–1.48); p=0.012; and aOR=1.48 (1.05–2.09); p=0.027, respectively]. Serum IL-6 levels are important predictors of all-cause mortality in this adult urban sub-Saharan African cART-treated population. Future translational studies are warranted to better elucidate pathophysiology and inform the design of novel interventions to ameliorate the risk of death among these “at-risk” individuals.
doi:10.1089/aid.2012.0309
PMCID: PMC3685692  PMID: 23590237
22.  Short Communication: Effect of Short-Course Antenatal Zidovudine and Single-Dose Nevirapine on the BED Capture Enzyme Immunoassay Levels in HIV Type 1 Subtype C Infection 
Abstract
Cross-sectional prevalence studies based on immunoassays that discriminate between recent and long-term infections, such as the BED assay, have been widely used to estimate HIV incidence. However, individuals receiving highly active antiretroviral therapy tend to have lower BED levels and are associated with a higher risk for being mistakenly classified as recent infections. To assess the effect of short-term antenatal zidovudine (ZDV) and single-dose nevirapine (sdNVP) on the BED levels in HIV-1C infection, we measured longitudinal BED normalized optical density (OD-n) levels using stored plasma samples collected prenatally and postnatally from 159 pregnant HIV-infected women in Botswana who participated in the randomized clinical Mother-to-Child-Prevention study, the Mashi study. All women received ZDV from 34 weeks gestation through delivery and were randomized to receive either sdNVP or placebo during labor. Among 159 subjects, the OD-n levels decreased from baseline to delivery in 93 subjects (p=0.039), suggesting that short-course ZDV may decrease OD-n levels. sdNVP at delivery did not affect longitudinal BED OD-n levels postdelivery. However, sdNVP appeared to modify the association between CD4 count at delivery and OD-n levels postdelivery. When estimating HIV incidence with the BED assay, special care may be required regarding women who received short-term ZDV for prevention of mother-to-child transmission.
doi:10.1089/aid.2012.0294
PMCID: PMC3653368  PMID: 23521375
24.  A Randomized Trial of Mogen Clamp versus Plastibell for Neonatal Male Circumcision in Botswana 
Background
Male circumcision can reduce the risk of heterosexually-acquired HIV-1 infection in men. Neonatal male circumcision (NMC) has many potential advantages over circumcision at older ages but little is known about its feasibility and safety in resource-limited settings.
Methods
We performed a randomized trial in southeastern Botswana of Mogen clamp and Plastibell, two commonly used devices for NMC. Follow-up visits occurred at six weeks and four months postpartum. Adverse events, parental satisfaction and staff impressions were recorded.
Results
Of 302 male neonates randomized, 300 (99%) underwent circumcision, 153 (51%) with Mogen clamp and 147 (49%) with Plastibell. There were no major adverse events in the Mogen clamp arm but there were two major adverse events in the Plastibell arm (both were a proximally migrated ring that had to be removed by study staff). Minor adverse events were more common with the Mogen clamp compared with the Plastibell, specifically removal of too little skin and formation of skin bridges or adhesions (12 vs. 1 and 11 vs. 3, respectively, all P<0.05). Five (3%) infants in the Mogen clamp arm and none in the Plastibell arm had minor bleeding (P=0.03). More than 94% of mothers reported being highly or completely satisfied with the procedure.
Conclusions
NMC can be performed in Botswana with a low rate of adverse events and high parental satisfaction. Although the risk of migration and retention of the Plastibell is small, the Mogen clamp may be safer for NMC in regions where immediate emergent medical attention is not available.
doi:10.1097/QAI.0b013e318285d449
PMCID: PMC3683122  PMID: 23314413
25.  Plasma Viral Loads During Early HIV-1 Infection Are Similar in Subtype C– and Non-Subtype C–Infected African Seroconverters 
The Journal of Infectious Diseases  2013;207(7):1166-1170.
Recent data suggest that infection with human immunodeficiency virus type 1 (HIV-1) subtype C results in prolonged high-level viremia (>5 log10 copies/mL) during early infection. We examined the relationship between HIV-1 subtype and plasma viremia among 153 African seroconverters. Mean setpoint viral loads were similar for C and non-C subtypes: 4.36 vs 4.42 log10 copies/mL (P = .61). The proportion of subtype C–infected participants with viral loads >5 log10 copies/mL was not greater than the proportion for those with non-C infection. Our data do not support the hypothesis that higher early viral load accounts for the rapid spread of HIV-1 subtype C in southern Africa.
doi:10.1093/infdis/jit015
PMCID: PMC3583276  PMID: 23315322
HIV-1; group M subtype; plasma viral load; early infection; Africa

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