SELECTED ABSTRCTS:
MoOa0108 High prevalence of undetected, acute HIV infection in a South African primary care clinic
Stevens W.1, Akkers E.2, Myers M.3, Motloung T. 3, Pilcher C.4, Venter F. 3
1University of Witwatersrand and National Health Laboratory Services, Johannesburg, South Africa, 2University of Witwatersrand, Johannesburg, South
Africa, 3Reproductive Health Research Unit, University of Witwatersrand, Johannesburg, South Africa, 4University of North Carolina, Chapel Hill, United
States of America
Introduction: Primary HIV infection (PHI) is rarely diagnosed despite a high HIV prevalence in South Africa. This phase is the most infectious stage of the disease and identification is deemed important for both prevention and treatment strategies. This cross sectional study assesses the prevalence ofantibody-negative PHI among South African men and women attending a primary health care clinic for treatment of sexually transmitted infections or toascertain their HIV status (VCT). The study also addresses the feasibility and impact of nucleic acid amplification pooling testing strategies in adeveloping world setting.
Methods: Clinic attendees were enrolled sequentially during the period of April to October 2004. Basic demographic information was collected and HIV
ELISA confirmatory testing was conducted in an anonymous, unlinked fashion. HIV antibody negative or indeterminate subjects had plasma stored for pooling and subsequent nucleic acid testing using the Roche MONITOR HIV-1 version 1.5 assay.
Results: A total of 1906 consecutive individuals were recruited to the study reflecting a relatively equal gender distribution. 672 individuals (35.2%) were HIV ELISA antibody positive. Of the 1200 HIV negative samples pooled, 3 of the pools of 100 specimens were positive for HIV-1 RNA, 3 were positive inthe pools of 50, and 7 pools of 10 were positive. Individual sample testing revealed 8 HIV RNA samples positive. 4 of 11 indeterminate HIV ELISAsamples were also positive for HIV RNA. The total number of acute HIV infections was thus 12.
Conclusions: A significant number of individuals were identified in this study as having acute primary HIV infection (0.99%), translating into an incidencerate per year of 12.9%. (C.I.: 11.01 to 14.12%). The feasibility of using pooling nucleic acid amplification testing strategies for high risk populations locally was confirmed.
MoOa0107 - Early detection of HIV infection in discordant heterosexual couples in Africa
Allen S. 1, Rwanda/Zambia HIV Research Group s.1
1EmoryUniversityRollinsSchool of Public Health, Atlanta, United States of America
Introduction: The early infection period is of interest for studies of pathogenesis. Early detection is also critical as an endpoint in clinical trials of prevention interventions. Strategies to increase identification of new infections include shorter testing intervals and antigen detection methods.
Methods: HIV discordant couples are enrolled though a couples’ VCT center and followed at 3-month intervals. The HIV negative partner is serologically tested with rapid HIV tests (Abbott Determine and Trinity Biotech Capillus), and plasma set aside for weekly p24Ag screening (Beckman-Coulter).
Antibody positive patients are counseled and additional samples taken of blood and genital fluids from both partners. Antibody negative individuals that are p24Ag+ are called in for repeat testing and sample collection. The p24Ag is considered positive at 3x the calculated cutoff for the EIA run.
Results: The seroconversion rate in counseled HIV discordant Zambian couples is 7-8/100 PY. Of 106 seroconvertors identified in 30 months of the study, 24 (23%) were p24Ag+. Six of these were antibody positive with two rapid tests at the time p24Ag was detected, the remaining 18 were antibodynegative. All 18 were antibody positive when they returned for repeat testing and sample collection, but only 1 of the 18 was still p24Ag+ at re-draw.
Conclusions: In a cohort with a seroconversion rate of approximately 2% per 3-month interval, one quarter of new infections can be identified during the early, p24Ag+ phase. The main obstacle to detection is the short duration of the antigen positive window, rather than the sensitivity of the antigen test.
Because increasing the frequency of study visits would result in decreased retention,the best strategy for obtaining study samples in early infection is more frequent batching of p24Ag testing and same-day invitations for re-draw.
WeFo0204 - E-184V study. Lamivudine monotherapy vs treatment interruption in failing HIV-1 infected subjects, harbouring the M184V mutation: 48-week final results
Castagna A. 1, Danise A. 1, Menzo S.2, Galli L. 1, Boeri E. 1, Gianotti N. 1, Carini E. 1, Tiberi S. 1, Cernuschi M. 1, Hasson H. 1, Mammarella M. 2, Guffanti M. 1,
Seminari E. 1, Clementi M. 1, Lazzarin A. 1
1Vita-Salute San Raffaele University, Milan, Italy, 2University of Marche, Ancona, Italy
Introduction: In pts with treatment failure, maintaining a virus with M184V mutation may allow a decline in CD4 cells slower than therapy interruption.
Aim of the study was to assess the frequency of immunological failure (CD4<350 cells/µL) (IF)/clinical failure (occurrence of first B or C CDC event) (CF)in failing pts who stop treatment or receive 3TC monotherapy.
Methods: This prospective, open-label, 48-week pilot study randomised 50 pts failing 3TC containing HAART, requesting therapy interruption (TI), with CD4>500 cells/µL, HIV-RNA>1000 cp/mL and with M184V mutation to stop treatment (TI-group) or to receive lamivudine 300 mg QD monotherapy (3TCgroup).
Replicative capacity was tested using a recombinant phenotypic method. Primary analysis was ITT/r.
Results: At screening, TI-group and 3TC-group median (IQR) CD4 number, CD4 percentage, HIV-RNA log10, nadir CD4 number were 629(563-768),
27.6(25.2-32), 3.78(3.33-4.30), 260(155-350), and 620(583-708), 24.7(19.3-28.8), 3.91(3.41-4.11), 283(250-341), respectively. 17/25 pts (68%, 95%CI:
48-83) in TI-group and 11/25 pts (44%, 95%CI: 24-65) in 3TC-group discontinued the study because of IF/CF in all but one pt in each group. CF occurred
in 2/25(8%) pts in TI-group only (one oesophageal candidiasis and one PID). At week 48 mean (95%CI) CD4 number, CD4 percentage, HIV-RNA log10 changes from BL were -189(-236,-141), -7.8(-9.5,-6.1), 1.23(0.96,1.5) in TI-group and -143(-202,-83), -4.3(-6.4,-2.3) (p=0.003), 0.67(0.48,0.86) (p=0.001)in 3TC-group. Median (IQR) BL and 48 week (or discontinuation) number of NRTI, NNRTI and PI resistance mutations were 4(2-6), 1(0-1), 2(1-7) and 0(0-1), 0(0-0), 1(0-2) in TI-group; 5(4-5), 1(0-1), 3(0-6) and 3(2-4), 0(0-1), 2(0-4) in 3TC-group. Increase in number of resistance mutations was never observed. Median (IQR) fold replicative capacity recovery (48-week/BL p24Ag ratio) was 9.75(3.15-26.12) in TI-group and 2.36(1.02-6.48) in 3TC-group.
Conclusions: 3TC monotherapy induces less immunological and clinical failure than TI. This strategy is associated with maintenance of reduced viral fitness, low viral rebound and reduction of resistance mutations.
TuFo0106 - Characterization of anemia in HIV-infected (HIV+) subjects treated with antiretroviral therapy (ART) with and without zidovudine (+/-
ZDV) in 54 clinical trials
Edwards M. 1, Burkle W. 1, Cutrell A. 1, Liao Q. 1, Brothers C. 1, Hernandez J. 1
1GlaxoSmithKline R&D, Research Triangle Park, North Carolina, United States of America
Introduction: Hematotoxicity (mainly anemia and neutropenia) is reported in HIV+ subjects, including those treated with ZDV. This ZDV-associated toxicity is considered dose related. Approximately 3% of subjects report moderate/severe anemia (DAIDS 1992 grades 2/4) at the currently approveddose. We performed an analysis of data from 54 trials (>12,000 subjects treated with ART +/- ZDV) to evaluate the incidence and severity of anemia.
Methods: All GSK-sponsored trials with ³24 weeks of ART finished from January 1995 to January 2004 were analyzed. Anemia was identified by Hb levels <normal, and classified with the DAIDS scale. Descriptive statistics were summarized for naïve and experienced subjects treated +/-ZDV.
Results: Baseline demographics and characteristics were comparable between subjects treated with (5174 subjects) and without (7511 subjects) ZDV.
71% and 42% of subjects respectively were ART-naive. The incidence of grade 2/4 anemia in naive subjects was similar in those receiving ZDV (1.5%,
95%CI [1.1%,1.8%]) versus those not receiving ZDV (1.3%, 95%CI [0.9%,1.7%]). In experienced subjects, the incidence of anemia was higher, (p<0.01),
in those receiving ZDV (1.7%, 95%CI [1.1%,2.4%]) than in those not receiving ZDV (0.8%, 95%CI [0.5%,1.1%]). When subjects receiving ZDV were classified as receiving ZDV as a separate drug vs. as part of a fixed combination tablet (Combivir [COM, ZDV 300mg/Lamivudine 150mg] or Trizivir [TZV,
ABC 300mg/Lamivudine 150mg/ZDV 300mg]) incidences of anemia were 2.0% (95%CI [1.5%,2.6%]) for ZDV and 1.1% (95%CI [0.7%,1.5%]) for COM/ TZV. Severe anemia (grade 3/4) was documented in 1.0% of naïve and in 1.0% of experienced subjects taking ZDV compared to 0.7% and 0.4% ofsubjects not taking ZDV.
Conclusions: The overall incidence of anemia in this cohort was low (1%). Subjects treated with ZDV had a higher incidence of anemia compared tosubjects not treated with ZDV. This incidence, however, was low and appeared to be lower when COM/TZV were used.
TuOa0304 - Acceptability of routine HIV testing in antenatal services in Zimbabwe
Perez F. 1, Zvandaziva C.2, Engelsmann B.3, Marchand D. 1, Dabis F.1
1ISPED - Université Victor Segalen Bordeaux 2, Bordeaux, France, 2Consultant, Harare, Zimbabwe, 3ISPED-Zimbabwe, Harare, Zimbabwe
Introduction: Mother-to-child transmission is the most important source of HIV infection in children. Low uptake of prevention of mother-to-childtransmission of HIV (PMTCT) interventions requires new approaches to prevent missed opportunities. Routine HIV testing (“opt-out”) in antenatal care
(ANC) has been reported to improve results of PMTCT interventions. The objective was to determine the acceptability of the opt-out strategy for HIVscreening during pregnancy in Zimbabwe, a high HIV prevalence country.
Methods: A descriptive cross sectional survey was conducted in six PMTCT sites. A set of four questionnaires was applied to interview 520 women overa three-month period. Women were identified at either postnatal services or in the OI clinic.
Results: Of 520 women sampled, 285 women (55%) had been HIV tested during pregnancy. Unemployment of partner (p=<0.001), primary education orlower (p= 0.02), not receiving group education (p<0.001) or pre-test counselling (p<0.001) and having attended less then six ANC visits (p=<0.001) wereassociated with not having been HIV tested. Women with knowledge of PMTCT were more likely to be HIV-tested (p<0.001). Amongst the 235 womennot HIV-tested in ANC, 80% would accept HIV-testing if routine testing was introduced in ANC services. Factors associated with accepting the opt-outapproach were, being married (p=0.03), secondary education or more (p=0.03) and having received group education (p=<0.001). 41 women would stillopt-out and refuse HIV-testing mainly because they fear knowing their HIV status and need to have partner consent.
Conclusions: Introduction of routine HIV testing in antenatal care is acceptable to most women and would increase uptake of PMTCT services. InZimbabwe, where 25% of pregnant women are HIV-infected, introduction of these strategies would have a far reaching public health impact. Issuesregarding, stigma, quality of post-testing counselling and staffing will need to be considered.
MoOa0203 - 6-month immunological response with HAART containing Nevirapine in HIV-infected women post exposure to single dose ofNevirapine for PMTCT. The MTCT-Plus Initiave in Abidjan, Côte d’Ivoire (2003-2005)
Bedikou G.1, Viho I. 1, Tonwe-Gold B. 1, Coffie J.P.2, Amani-Bosse C. 1, Allou G. 1, Sakarovitch C. 2, Toure S. 1, Ekouevi D.K. 1, Leroy V. 2, Abrams E.J.3,
Dabis F. 2
1Programme MTCT-Plus, Aconda, Abidjan, Côte D'Ivoire, 2Unité INSERM 593, Institut De Santé Publique, Epidémiologie Et Développement (ISPED),
Bordeaux, France, 3The MTCT-Plus Initiative, Mailman School Of Public Healths, Columbia University, New-York, United States of America
Introduction: Single-dose nevirapine (sdNVP) is known to induce viral resistance when used to prevent mother-to-child of HIV-1 transmission (PMTCT).
In resource-limited settings NNRTI based HAART, using NVP, is the WHO-recommended first-line regimen for adults. We studied the immunologicalresponse in women treated with NVP-based HAART according to their previous exposure to sdNVP (sdNVP+) for PMTCT in Abidjan.
Methods: MTCT-Plus is a multi-country care and treatment program built upon existing PMTCT services. It provides pregnant and postpartum women, their partners and children with family-centered HIV care including HAART when they meet WHO eligibility criteria (WHO stage 4, stage 2 or 3 with CD4count <350/mm3 and CD4<200/mm3).
Results: From August 2003 to February 2005, 530 women were enrolled and 209 HIV-infected women including 92 (44%) pregnant women were initiated HAART. Among these women, 115 (55%) had received previously sdNVP for PMTCT including 49 with ZDV and 66 with ZDV+3TC. The delay inmedian between PMTCT intervention and HAART initiation was 19 months. The median CD4 count was 191/mm3. The first-line regimens initiated by thewomen were ZDV+3TC+NVP (93%), D4T+3TC+NVP (3%) and other regimens (4%). Median follow-up on HAART was 7.5 months. At 6 months ontreatment, the CD4 count increased in median by 205 cells/mm3; IQR [125-313/mm3] in 127 women who had measurements available. No statisticaldifference in CD4 count was found between the 64 women sdNVP+ and the 63 women sdNVP- (189/mm3 vs 222/mm3, p=0.53). At 12 months, the CD4count increased in median of 307/mm3 [188-451] in women sdNVP+ (n=15) and 289/mm3 [161-364] (n=27) in women sdNVP- (p=0.37).
Conclusions: The 6-month immunological response was similar in women previously exposed or not to sdNVP before initiating HAART. Further followup
is necessary to fully assess the long-term, impact of sdNVP used for PMTCT on the success of NNRTI containing therapeutic regimens.
TuOa0302 Can we scale up national prevention of mother-to-child transmission (PMTCT) program in low resources settings ? Lessons learned and challenges from Cameroon’s experience
Tsague L.1, Njom Nlend A.2, Zoung-Kanyi Bissek A.1, Tchendjou P.3, Tejiokem M.3, Tih P.4, Tene G.5, Eteki N.6, Tonye R.6, Same Ekobo C.7, Engozo’o A.1, Nokouni M.1, Koulla S.8, Penda I.9, Tchendje T.10, Bella A.1
1Directorate for Disease Control, Ministry of Public Health, Yaoundé, Cameroon, 2Central Technical Group of National Aids Control Committee, Yaoundé, Cameroon, 3Centre Pasteur du Cameroun, Yaoundé, Cameroon, 4Cameroon Baptist Convention Health Board, Bamenda, Cameroon, 5Chantal Biya Foundation, Yaoundé, Cameroon, 6 Yaounde Central Hospital, Yaoundé, Cameroon, 7Essos Medical Center, Yaoundé, Cameroon, 8Central Hospital of Yaounde, Yaoundé, Cameroon, 9Laquinitinie Hospital Douala, Douala, Cameroon, 10Affixe, , Yaoundé, Cameroon
Introduction: Successful results of the pilot PMTCT project in 2000-2001 justified the extension of the program to all the country to reduce by 50% the incidence of HIV infection in children by offering PMTCT package in at least 80% of health districts by 2005.
Methods: A combination of “top-bottom” and “bottom-up” strategies in the framework of a scaling up plan were used to ensure a proper coverage of the health services. Partnership with the private sector was encouraged through agreement with the MOH. A focal PMTCT officer was defined for the management of the program at the provincial. An integrated procurement and supply system for ARV and HIV tests was designed. Training of senior counsellor trainers was organised for all the ten provinces. A “district approach” was developed to improve the coverage and the integration of PMTCT services at the district level.
Results: The program moved from less than 5% coverage of health district in 2001 to 60% by the end of 2004 with a variability of number of PMTCT sites by provinces (average per province : 27 sites, range : 4-61). From 2001 to 2004, 2,500 health providers were trained, and 200,000 pregnant women counselled for HIV in ANC. The average acceptance rate nationwide is 70% (range : 16-95%). In 2003, 70% (57,000/82,000) of pregnant women accepted to be tested for HIV in ANC and 7.5% were found positive. Among them, 63% was effectively treated with Nevirapine at delivery, and 70% of expected babies. An impact evaluation in babies at 18 months described a residual 10.6% risk of transmission.
Conclusions: The PMTCT program has effectively embarked into the scaling up phase, but some challenges remain: consolidate the existing activities and scaling up the interventions at the district level using the “district approach”, Improve into the community awareness and commitment for PMTCT.
TuOa0303Factors influencing the acceptance of HIV voluntary counselling and testing among pregnant women in Cameroon’s PMTCT program.
Tsague L.1, Njom Nlend A.2, Zoung-Kanyi A.C.1, Engozo’o A.1, Nokouni M.1, Tene G.3, Eteki N.4, Penda I.5, Same Ekobo C.6, Tejioken M.7, Tchendjou P.7, Tih P.8, Bella Hiag A.1
1Directorate of Disease Control, Ministry of Public Health, Yaounde, Cameroon, 2National AIDS Control Committee, Yaoundé, Cameroon, 3Chantal Biya Foundation, Yaoundé, Cameroon, 4Yaounde Central Hospital, Yaoundé, Cameroon, 5Laquintini Hospital Douala, Douala, Cameroon, 6National Insurance Fund Hospital, Yaoundé, Cameroon, 7Centre Pasteur du Cameroun, Yaoundé, Cameroon, 8Cameroon Baptist Convention Health Board, Bamenda, Cameroon
Introduction: Cameroon’s PMTCT program started scaling up its interventions in year 2002. Since then, a great variation in HIV testing uptake (range : 16%-95%) has been described between differents sites. We have conducted operational research in some PMTCT sites to identify why there has been such a diversity of acceptancein order to give an appropriate response.
Methods: A cross sectional study using a randomised sample of 38 PMTCT sites in all the 10 provinces was conducted. Data were collected using a standardized questionnaire, administered to the PMTCT medical team. Qualitative and quantitative data about their PTMCT activities were collected.
Results: From January to July 2003, 8,270 pregnant women were counselled for HIV with a median HIV testing uptake (HIV TU) of 65.5% (95% CI: 64.5-66.5%). The HIVTU varied from 9% to 98% according to site. The median duration of program implementation was 8 months (range: 2-46) and was correlated with an increase in HIVTU (p<0.01). 78.5%(109/139) of counsellors in PMTCT sites were trained. Median HIVTU in sites with more than 5 trained counsellors was significantly higher than in sites with less than 5 (85% versus 59%; p=0.02). Average cost of HIV testing was $2.2 (range: 0-$9.4). Median HIVTU were 75% and 59% in sites offering HIV testing at a cost less or more than $2.72 respectively. There was no association between the cost of HIV testing and the HIVTU (p=0.29), although a correlation was observed (r=0.332, p=0.032).
Conclusions: The number of trained counsellors seems to influence HIVTU in our program more than the cost of HIV testing which is only correlated. Emphasis should be made on increasing the number of well trained cousellors at PMTCT sites to ensure a quality comprehensive PMTCT package and increase the number of pregnant women accepting HIV testing.
TuFo0204 - Addition of short course Combivir (CBV) to single dose Viramune (sdNVP) for the prevention of mother-to-child transmission
(pMTCT) of HIV-1 can significantly decrease the subsequent development of maternal and paediatric NNRTI-resistant virus
McIntyre J.A.1, Martinson N.1, Gray G.E.1, Hopley M.2, Kimura T.3, Robinson P.3, Mayers D.3
1Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa, 2Boehringer Ingelheim ZA, Johannesburg, South Africa,
3Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, United States of America
Introduction: Single-dose nevirapine (sdNVP) given at the time of delivery has decreased MTCT in resource-poor settings, but concerns have been
raised about development of NNRTI-resistance limiting future treatment. A trial of sdNVP+short course CBV was conducted to determine whether postpartum
HIV-1 resistance could be reduced.
Methods: A prospective, randomized three-arm study conducted in South Africa compares sdNVP, sdNVP+4 days CBV and sdNVP+7 days CBV for