[Show abstract][Hide abstract] ABSTRACT: To review a quality control and quality assurance (QC/QA) model established to ensure the validity and reliability of collection, storage and analysis of biological outcome data, and to promote good laboratory practices (GLPs) and sustained operational improvements in international clinical laboratories, we conducted a two-arm randomized community-level HIV behavioural intervention trial in five countries: China, India, Peru, Russia and Zimbabwe. The trial was based on diffusion theory utilizing a Community Popular Opinion Leaders (CPOLs) intervention model with behavioural and biological outcomes. The QC/QA model was established by the Biological Outcome Workgroup, which collaborated with the Data Coordinating Center and John Hopkins University Reference Laboratory. Five international laboratories conducted chlamydia/gonorrhoea polymerase chain reaction (PRC)-based assays, herpes simplex virus type 2 enzyme immunoassay (EIA), syphilis serology (rapid plasma regain and Treponema pallidum particle agglutination assay, HIV serology (EIA/Western blot) and Trichomonas vaginalis culture. Data were collected at baseline, 12 and 24 months. Laboratory performance and infrastructure improved throughout the trial. Recommendations for improvement were consistently followed. Quality laboratories in resource-poor settings can be established, operating standards can be improved and certification can be obtained with consistent training, monitoring and technical support. Building collaborative partnership relations can establish a sustainable network for clinical trials, and can lead to accreditation and international laboratory development.
International Journal of STD & AIDS 11/2011; 22(11):645-52. DOI:10.1258/ijsa.2011.010527 · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Single-dose nevirapine (SD NVP) reduces intrapartum HIV-1 transmission, but nonnucleoside reverse transcription (NNRTI) resistance mutations can emerge. Population sequencing among 32 subtype C HIV-1-infected, SD NVP-exposed Zimbawean women demonstrated NNRTI resistance in 25/32 (78%) women: 23/30 (77%) at 2 weeks, 11/31 (35%) at 8 weeks, and 5/27 (19%) at 24 weeks. A total of 447 unique TA clones (median = 28 per time point), from four women with resistance at 8 weeks but wild-type virus by population sequence at 24 weeks, identified NNRTI mutations in a median of 76% (range: 55-96%) of individual clones at 2 weeks, 48% (range: 33-80%) at 8 weeks, and 5% (range: 0-15%) by 24 weeks. NNRTI mutations in breast milk clones at 2 and weeks from one woman varied significantly from plasma. Population sequencing underestimates the diversity of NNRTI resistance mutations within minority populations following SD NVP in subtype C HIV-1 viral RNA in plasma and breast milk.
AIDS Research and Human Retroviruses 09/2007; 23(8):1055-61. DOI:10.1089/aid.2007.0045 · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mother-to-child HIV prevention trials in sub-Saharan Africa use the US National Institutes of Health Division of AIDS (DAIDS) grading scale to monitor hematologic toxicity. A recent study of nevirapine prophylaxis given for 6 months in breast-feeding Zimbabwean infants reported several cases of relative neutropenia in clinically well infants, raising concerns of drug toxicity. However, the DAIDS tables are based on normal blood counts for white infants, although there is evidence that black African infants may have lower absolute neutrophil counts (ANCs) than white infants. To establish normal hematologic values in black Zimbabwean infants and to quantify the apparent prevalence of relative neutropenia in this population, we evaluated HIV-uninfected healthy infants born to HIV-uninfected women at birth, 10 days, 6 weeks, 3, and 4 months of life. A physical examination and blood count were performed at each visit, and an HIV test was performed at the final visit. The ANC values were graded using the DAIDS table. A total of 145 healthy term infants satisfied the inclusion criteria. The mean ANC values for Zimbabwean infants were less than half of the corresponding standard values at all 5 time points (P < 0.0001). Using the DAIDS table in use at the time that the blood was collected, 57% of these healthy infants had relative neutropenia of any grade at birth, followed by 29% at day 10, 53% at 6 weeks, 32% at 3 months, and 37% at 4 months of life. Our data indicate that relative neutropenia exists in healthy black Zimbabwean infants. The guidelines for identifying toxicity were changed in December 2004. However, even by the new DAIDS tables, 43%, 23%, 24%, 42%, and 43% of these healthy babies had relative neutropenia at the time of the 5 visits. Future HIV prevention and treatment trials in sub-Saharan Africa should use normal hematologic values derived from African infants to avoid the overestimation of antiretroviral drug toxicity.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this pilot project was to assess the feasibility and acceptability of voluntary counselling and HIV testing (VCT) by pregnant women using community volunteers in Zimbabwe to prevent mother to child transmission (MTCT) of HIV. From July 1999 to June 2001, a short-course zidovudine (ZDV)-based perinatal HIV prevention programme was initiated in two antenatal clinics. Community volunteers, recruited from local community organizations, underwent a two-week training course in VCT, which included HIV/AIDS facts, systematic counselling approach, and practical counselling techniques using scripts and role-play. Rapid HIV testing was performed after informed consent. Lay counsellors conducted individual pre- and post-test counselling for HIV. A total of 35 women community volunteers were trained in VCT; 34 graduated and committed to work four hours per week in the clinic. Of the 6051 pregnant women presenting for antenatal clinics (ANC), 1824 (30%) underwent pre-test counselling and 1547 (26%) were tested, and 429 (28%) were HIV infected. Overall, 1283 (83%) returned for their test results including 406 (95%) of HIV-infected women. Of the 406 HIV-infected women who collected their test results, only 203 (50%) opted for ZDV prophylaxis to prevent MTCT of HIV. Over the two-year study period, two counsellors died and three sought employment at other organizations. Adherence to duty roster was 97% and no breach of confidentiality was reported. Despite many challenges, VCT delivered by community volunteers is feasible and acceptable for pregnant women aiming to reduce their risk of transmitting HIV to their infants. This programme is being implemented at several urban and rural MTCT sites in Zimbabwe and can serve as a model for other resource-poor countries.
International Journal of STD & AIDS 12/2005; 16(11):755-9. DOI:10.1258/095646205774763090 · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Single-dose nevirapine reduces intrapartum human immunodeficiency virus 1 type (HIV-1) transmission but may also select for nonnucleoside reverse-transcriptase inhibitor (NNRTI) resistance in breast milk (BM) and plasma. Among 32 Zimbabwean women, median 8-week postpartum plasma and BM HIV-1 RNA levels were 4.57 and 2.13 log(10) copies/mL, respectively. BM samples from women with laboratory-diagnosed mastitis (defined as elevated BM Na(+) levels) were 5.4-fold more likely to have HIV-1 RNA levels above the median. BM RT sequences were not obtained for 12 women with BM HIV-1 RNA levels below the lower limit of detection of the assay used. In 20 paired BM and plasma samples, 65% of BM and 50% of plasma RT sequences had NNRTI-resistance mutations, with divergent mutation patterns.
The Journal of Infectious Diseases 11/2005; 192(7):1260-4. DOI:10.1086/444424 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The prevalence of cervical infection with diverse HPV types and an association with mother-to-child transmission (MTCT) among pregnant women with subtype C HIV-1 infection in Southern Africa is not defined.
HIV-1 (subtype C) positive pregnant women from a peri-urban high density setting in Zimbabwe were evaluated for prevalence and type of HPV infection by assays from cervical swab samples. Polymerase chain reaction (PCR) was performed followed by a generic (or “consensus”) HPV probe using DNA hybridization. Consensus-probe positive samples were re-probed for 29 individual HPV types. Infant infection status was determined for 45 infants by ELISA at 12-18 months and PCR assays at birth and 2-weeks.
Cervicovaginal samples from n=59 patients were assessed for presence and type of HPV. Two were excluded from analysis because of insufficient DNA. With the generic probe, 84% (48/57) of samples were positive for presence of HPV. Re-probing identified 25 unique types in 34 (71%). HPV 58 and 59 (16- and 18-like high-risk types, respectively) were the most frequent types, each found in 9 women, followed by HPV 61 and 66, each found in 8 women. Six of 45 (13%) evaluable infants acquired HIV infection. An 18-like HPV type (26, 59, 68, 69, or 70) or a 56-like HPV type (53, 56, or 66) was identified in 5 of 6 mothers (83%). Among 39 women whose infants were not infected an 18-like or 56-like HPV type was present in n=13 (33%) (P = .031). A 16-like HPV type (31, 33, or 58) was present in an additional 4 mothers of HIV-negative infants.
An unusually high proportion of HIV-positive women in a peri-urban setting in Zimbabwe show evidence of HPV infection in cervical swab samples, with broad diversity of HPV types. This preliminary assessment of HPV carriage warrants further study of HPV types, HIV cervical shedding and the association between HPV and MTCT of subtype C HIV-1.
Infectious Diseases Society of America 2005 Annual Meeting; 10/2005