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author:("thiol, ibu")
1.  Strategies for recruiting injection drug users for HIV prevention services in Delhi, India 
We utilized multiple recruitment approaches to recruit IDUs in a longitudinal cohort study to examine HIV incidence and behavior change pre- and post-introduction of comprehensive HIV prevention services.
IDUs were recruited through peer referral, targeted outreach by outreach workers (ORWs) and as walk-in clients at drop-in centers. Participants received monetary compensation for participation (USD 0.80). Participants were given recruitment coupons to recruit peers (regardless of recruitment method). For peer referral, participants received a food coupon, as secondary compensation, for each peer he/she successfully recruited. We report the profile of IDUs by recruitment method, based on the baseline behavioral survey and HIV test results. Cost per IDU recruited by recruitment method was also calculated.
A total of 3,818 IDUs were recruited between May 2011 and October 2011. More than half of the study participants were recruited through targeted outreach (ORW: 53.6%; peer-referral: 26.3%; walk-ins: 20.1%). Of the participants who were given recruitment coupons, 92.7% recruited no peers. Those who successfully recruited at least one peer were significantly more likely to be in a stable living accommodation compared to those who did not recruit any peers (51.1% versus 42.7%; p < 0.05). Only 45.9% of the food coupons were claimed for successful recruitment of peers. Peer-referred IDUs were more likely to be living with family or relatives (50.7% versus ORW: 40.1% and walk-in: 39.8%; p < 0.001) rather than on the street or shared housings compared to the other two recruitment modes. Walk-ins were more likely than peer-referred and ORW-referred IDUs to be HIV-positive (walk-ins: 26.1%; peer-referred: 19.1%; ORW: 19.9%; p < 0.01) and have risky injection practices (walk-ins: 62.2%; ORW: 57.0%; peer-referred: 58.6%; p < 0.05). The cost per IDU recruited through ORW referral method was the most costly at USD 16.30, followed by peer-referral at USD 8.40 and walk-in at USD 7.50.
When recruiting a large number of IDUs, using multiple recruitment modes is ideal with regard to diversification of IDU characteristics and risk profile. Although it was the most costly, ORW recruitment was more effective than the other two methods. Lack of monetary compensation for successful recruitment of peers may have hampered peer-referral.
PMCID: PMC3849590  PMID: 24063610
Injection drug user; HIV prevention; Out-reach worker; Peer-referral; Harm-reduction
2.  Infant Feeding Practices Were Not Associated with Breast Milk HIV-1 RNA Levels in a Randomized Clinical Trial in Botswana 
AIDS and behavior  2012;16(5):1260-1264.
Exclusive breastfeeding has been associated with a reduced risk of late vertical HIV transmission as compared to an infant diet composed of breast milk mixed with supplemental foods or liquids. Hypothesized mechanisms include increased infectivity of breast milk from mothers who practice mixed breastfeeding (MBF), or mechanisms such as increased gastrointestinal permeability in the infant caused by mixed feeding. It has been proposed that MBF may result in subclinical mastitis and higher breast milk HIV titers. However, little is known about the relationship between feeding strategy and breast milk viral load. We measured the HIV-1 concentration in breast milk in a sub-cohort of women enrolled in a mother-to-child HIV transmission prevention trial (the "Mashi" study). We report no observed relationship between MBF and measured breast milk viral RNA load. Our findings suggest that the increased transmission risk associated with higher breast milk HIV-1 RNA during MBF is unlikely.
PMCID: PMC3523667  PMID: 21901486
exclusive; mixed; PMTCT; breast feeding; vertical HIV transmission
3.  Minor resistant variants in nevirapine-exposed infants may predict virologic failure on nevirapine-containing ART 
Single-dose nevirapine (sdNVP) is widely used to prevent mother-to-child transmission (PMTCT) of HIV-1. This may result in NVP resistance in both mother and infant. The significance of low levels of NVP resistance mutations in infants treated with NVP-containing antiretroviral treatment (ART) is unknown.
To determine the presence of pre-treatment NVP resistance in HIV-infected infants with and without prior NVP exposure.
Study Design
33 HIV-1-infected infants in a PMTCT trial received NVP-containing ART (26 infants with prior NVP exposure). Plasma and buffy coat samples obtained prior to ART initiation were evaluated for drug resistance by bulk sequencing and allele-specific PCR (ASPCR).
ViroSeq™ identified NVP resistance in 3 of 33 infants; all failed first-line therapy. Pre-ART plasma NVP resistance by ASPCR was detected in 9 of 16 children experiencing virologic failure compared to 4 of 17 children without virologic failure (risk ratio 2.4, CI 0.94-7.8, p=0.08). Proviral resistance was not associated with virologic failure (risk ratio 1.2, CI 0.8-2.0, p= 0.40). In the nevirapine-exposed infants, those who started ART before 7 months had higher risk of virologic failure (RR 2.3; CI 0.96-9.2; p=0.11).
Low level drug resistance detected in plasma after NVP exposure prior to ART initiation may be associated with virologic failure on ART, while resistance in the DNA reservoir was not predictive of treatment outcome.
PMCID: PMC2909836  PMID: 20427228
HIV; minor variant; drug resistance; nevirapine; PMTCT
4.  Temporal Reduction of HIV Type 1 Viral Load in Breast Milk by Single-Dose Nevirapine during Prevention of MTCT 
AIDS Research and Human Retroviruses  2009;25(12):1261-1264.
Short-course zidovudine (ZDV) with or without a single dose of nevirapine (sdNVP) is widely used to prevent mother-to-child HIV transmission (PMTCT). However, more data on viral load in breast milk following pMTCT regimens are needed. In a randomized PMTCT study in Botswana, in which half of the women received sdNVP in labor, stored samples from mothers assigned to breastfeed were analyzed for HIV-1 RNA in breast milk supernatant. A total of 527 samples from 282 women, collected at delivery, 2 weeks, 2 months, and 5 months postpartum were available for testing. Cell-free breast milk HIV-1 RNA was detectable (>40 copies/ml) in 44.8% (236/527) of samples analyzed. Women randomized to sdNVP + ZDV were more likely to have undetectable breast milk viral loads at 2 weeks postpartum compared with those who received ZDV alone (67.8% vs. 38.5%, p = 0.002). By 2 months postpartum the difference between study arms disappeared, and 43.8% of women who received sdNVP + ZDV had undetectable HIV-1 RNA compared to 53.8% of the ZDV alone group (p = 0.19) and 60.5% vs. 64.5%, respectively, at month 5 (p = 0.61.) The addition of sdNVP to antenatal short-course AZT resulted in significantly reduced breast milk viral loads at 2 weeks postpartum suggesting a reduced risk of MTCT during the early postpartum period. However, viral loads in both study arms were comparable at 2 and 5 months postpartum, suggesting that the receipt of sdNVP in labor may defer rather than blunt the postpartum viral load rebound seen in breast milk after the discontinuation of ZDV.
PMCID: PMC2828251  PMID: 20001515
5.  HIV-1 Subtype C-Infected Individuals Maintaining High Viral Load as Potential Targets for the “Test-and-Treat” Approach to Reduce HIV Transmission 
PLoS ONE  2010;5(4):e10148.
The first aim of the study is to assess the distribution of HIV-1 RNA levels in subtype C infection. Among 4,348 drug-naïve HIV-positive individuals participating in clinical studies in Botswana, the median baseline plasma HIV-1 RNA levels differed between the general population cohorts (4.1–4.2 log10) and cART-initiating cohorts (5.1–5.3 log10) by about one log10. The proportion of individuals with high (≥50,000 (4.7 log10) copies/ml) HIV-1 RNA levels ranged from 24%–28% in the general HIV-positive population cohorts to 65%–83% in cART-initiating cohorts. The second aim is to estimate the proportion of individuals who maintain high HIV-1 RNA levels for an extended time and the duration of this period. For this analysis, we estimate the proportion of individuals who could be identified by repeated 6- vs. 12-month-interval HIV testing, as well as the potential reduction of HIV transmission time that can be achieved by testing and ARV treating. Longitudinal analysis of 42 seroconverters revealed that 33% (95% CI: 20%–50%) of individuals maintain high HIV-1 RNA levels for at least 180 days post seroconversion (p/s) and the median duration of high viral load period was 350 (269; 428) days p/s. We found that it would be possible to identify all HIV-infected individuals with viral load ≥50,000 (4.7 log10) copies/ml using repeated six-month-interval HIV testing. Assuming individuals with high viral load initiate cART after being identified, the period of high transmissibility due to high viral load can potentially be reduced by 77% (95% CI: 71%–82%). Therefore, if HIV-infected individuals maintaining high levels of plasma HIV-1 RNA for extended period of time contribute disproportionally to HIV transmission, a modified “test-and-treat” strategy targeting such individuals by repeated HIV testing (followed by initiation of cART) might be a useful public health strategy for mitigating the HIV epidemic in some communities.
PMCID: PMC2853582  PMID: 20405044
6.  Hematologic and hepatic toxicities associated with antenatal and postnatal exposure to maternal HAART among infants 
AIDS (London, England)  2008;22(13):1633-1640.
To assess hematologic and hepatic toxicities associated with in utero and breastfeeding exposure to maternal HAART among infants in Botswana.
A nested cohort study within a randomized clinical trial (the Mashi Study). Laboratory toxicities among infants born to women who initiated HAART before delivery were compared to toxicities among those born to women who received zidovudine (ZDV) plus a single dose of nevirapine (NVP) or placebo in labor. Infants were randomized to breastfeed with extended ZDV or to formula-feed.
Hemoglobin concentrations (HB), absolute neutrophil (ANC) and platelet (PLT) counts, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were recorded from birth to 7 months of age in infants. Grade 3 and 4 toxicities were compared by infant antiretroviral exposure status.
In utero exposure to maternal HAART was associated with increased risk for neutropenia in infants up to 1 month of age; 21.7% of HAART-exposed infants were neutropenic, compared with 5.5% of the infants exposed to ZDV (P<0.01). However, neutropenia was no longer associated with antenatal exposure to HAART after 1 month of age. Postnatal exposure to HAART was not associated with hematologic or hepatic toxicities. Laboratory toxicities were clinically asymptomatic in all but one infant.
Exposure to maternal HAART in utero may increase the risk for infant neutropenia, particularly among breastfed infants, but the clinical significance of this finding is uncertain. The lack of association between exposure to HAART through breastfeeding and long-term toxicities in infants is reassuring but deserves study in larger cohorts.
PMCID: PMC2664540  PMID: 18670224
HIV; breastfeeding; mother-to-child transmission; HAART; toxicity; Botswana
7.  Voluntary counseling and testing among post-partum women in Botswana 
Patient education and counseling  2006;65(3):296-302.
To determine uptake and socio-demographics predictors of acceptance of voluntary counseling and testing (VCT) among post-partum women in Botswana.
Women attending maternal and child health clinics for their first post-partum or well baby visit in 3 sites in Botswana were offered VCT after a written informed consent. A standardized questionnaire was used to collect socio-demographic characteristics and reasons for declining VCT.
From March 1999 to November 2000, we approached 1735 post-partum women. Only 937 (54%) of those approached accepted VCT. In multiple logistic regression analysis, younger maternal age, not being married, and less formal education were significant predictors of acceptance of VCT. Thirty percent of women who accepted VCT were HIV-positive
Our results indicated that in Botswana prior to the initiation of a government Mother to Child Transmission (MTCT) prevention program, younger, unmarried, and less educated post-partum women were more likely to undergo VCT.
Practice Implications
Our results have shown that interventions to improve VCT among post-partum women and more generally among women of reproductive age are warranted in Botswana. These interventions should account for differences such age, marital status, education and partner involvement to maximize VCT uptake.
PMCID: PMC1868467  PMID: 17029865
VCT; Post-partum women; HIV; Botswana
8.  Impact of Human Immunodeficiency Virus Type 1 Subtype C on Drug Resistance Mutations in Patients from Botswana Failing a Nelfinavir-Containing Regimen 
Among 16 human immunodeficiency virus-infected (subtype C) Batswana patients who failed nelfinavir (NFV)-containing regimens, the most prevalent mutation observed was D30N (54%), followed by L90M (31%). L89I, K20T/I, and E35D polymorphic changes were also identified. These findings suggest that subtype C viruses in Botswana may develop resistance to NFV via subtype-specific pathways.
PMCID: PMC1479146  PMID: 16723586
9.  Major Histocompatibility Complex Class II (HLA-DRB and -DQB) Allele Frequencies in Botswana: Association with Human Immunodeficiency Virus Type 1 Infection 
Southern Africa is facing an unprecedented public health crisis due to the high prevalence of human immunodeficiency virus type 1 (HIV-1). Vaccine development and testing efforts, mainly based on elicitation of HIV-specific T cells, are under way. To understand the role of human leukocyte antigen (HLA) class II alleles in HIV pathogenesis and to facilitate HLA-based HIV-1 vaccine design, we analyzed the frequencies of HLA class II alleles within the southern African country of Botswana. Common HLA class II alleles were identified within the Batswana population through the molecular genotyping of DRB and DQB1 loci. The DRB1 allele groups DRB1*01, DRB1*02/15, DRB1*03, DRB1*11, and DRB1*13 were encountered at frequencies above 20%. Within the DQB1 locus, DQB1*06 (47.7%) was the most common allele group, followed by DQB1*03 (39.2%) and DQB1*04 (25.8%). We found that DRB1*01 was more common in HIV-negative than in HIV-positive individuals and that those who expressed DRB1*08 had lower median viral loads. We demonstrate that the frequencies of certain HLA class II alleles in this Batswana population differ substantially from those in North American populations, including African-Americans. Common allele groups within Botswana cover large percentages of other African populations and could be targeted in regional vaccine designs.
PMCID: PMC1235800  PMID: 16148166
10.  A Microchip CD4 Counting Method for HIV Monitoring in Resource-Poor Settings 
PLoS Medicine  2005;2(7):e182.
More than 35 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 3 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed.
Methods and Findings
Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a miniaturized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r = 0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity.
Advances in the adaptation of new technologies to biomedical detection systems, such as the one described here, promise to make complex diagnostics for HIV and other infectious diseases a practical global reality.
A rapid affordable method for counting CD4 cells may be useful for management of HIV in resource poor settings.
PMCID: PMC1176233  PMID: 16013921
11.  Low CD4+ T-Lymphocyte Values in Human Immunodeficiency Virus-Negative Adults in Botswana 
CD4+-lymphocyte counts (LCs) play a crucial role in the management and monitoring of HIV infection. Variability in CD4+ LCs has been reported to occur as a result of measurement techniques and/or biological variations. We report on the CD4+ LCs of healthy human immunodeficiency virus (HIV)-seronegative adults in Botswana. Samples were obtained from HIV-seronegative blood donors. The median CD4+ LC was 726 cells/mm3 (for females, 782 cells/mm3; for males, 698 cells/mm3). The median CD8+ LC was 488 cells/mm3 (for females, 494 cells/mm3; for males, 485 cells/mm3). The median CD4+-to-CD8+ ratio was 1.57 (for females, 1.66; for males, 1.51). Our findings of low CD4+ LCs among HIV-negative adults in Botswana are significant and have important implications for the management of HIV disease in the population of this sub-Saharan African country.
PMCID: PMC515279  PMID: 15358655
12.  Molecular Epidemiology of Genital Chlamydia trachomatis Infection in High-Risk Women in Senegal, West Africa 
Journal of Clinical Microbiology  2000;38(1):138-145.
The prevalence and heterogeneity of Chlamydia trachomatis infections in a cohort of female sex workers in Dakar (Senegal) were determined by using endocervical-swab-based PCR DNA amplification assays. The overall prevalence of cervical chlamydial infection was 28.5% (206 of 722), and most of these infections were asymptomatic. An increased number of sexual partners was significantly associated with infection (adjusted odds ratio [AOR] = 1.37; 95% confidence interval [CI] = 1.06 to 1.77), while the presence of a yeast infection was negatively associated with chlamydial infection (AOR = 0.28; 95% CI = 0.10 to 0.83). Six different C. trachomatis genotypes were identified based on phylogenetic analysis of the omp1 gene sequences. Interestingly, genotype E predominated (47.6%) and was not associated with visible signs of cervical inflammation compared to non-E genotypes (P < 0.05). Overall, the high rate of asymptomatic C. trachomatis infection by genotype E may suggest genotype-specific properties that confer a transmission advantage in this high risk population.
PMCID: PMC86040  PMID: 10618077

Results 1-12 (12)