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1.  Prevalence of human papillomavirus genotypes and associated cervical squamous intraepithelial lesions in HIV-infected women in Botswana 
Journal of medical virology  2011;83(10):1689-1695.
Human papillomaviruses (HPV) constitute one of the most prevalent sexually transmitted infections and are the etiological agents for invasive cervical cancer, the predominant cancer among women in Botswana. However, the prevalence of HPV genotypes in Botswana has yet to be reported
139 endocervical swabs were taken at baseline from HIV-1 infected, HSV-2 seropositive women enrolled in a longitudinal cohort study designed to assess the influence of herpes simplex virus-2 (HSV-2) infection on genital tract shedding of HIV-1. Extracted DNA was evaluated for the presence of low-risk and high-risk HPV using the Roche Linear Array.
Genotyping identified HPV in 95 of 139 women of which 61/95 were infected with high-risk HPV and 56/95 with low-risk HPV. The median number of genotypes was 2 (IQR: 1–4). The most prevalent HPV genotype in HIV-infected women was HPV 58. Abnormal cervical cytology was detected in 87/127 women and was associated with contemporaneous HPV infection (RR=1.43, 95% CI: 1.05–1.93) (p=0.02).
HPV prevalence was high among HIV-infected women with infection by multiple genotypes being widespread. The associations attributed to specific oncogenic HPV subtypes and cervical squamous intraepithelial lesions presented here provide critical information to inform future vaccine policy within Botswana.
PMCID: PMC3156037  PMID: 21837784
HIV; Human Papillomavirus; co-infection; cervical cancer
2.  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
3.  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
4.  Viral Load and CD4+ T-Cell Dynamics in Primary HIV-1 Subtype C Infection 
Most knowledge of primary HIV-1 infection is based on subtype B studies, whereas the evolution of viral parameters in the early phase of HIV-1 subtype C infection is not well characterized.
The kinetics of viral RNA, proviral DNA, CD4+ T-cell count, and subsets of CD4+ T cells expressing CCR5 or CXCR4 were characterized in 8 acute and 62 recent subtype C infections over the first year postseroconversion.
The viral RNA peak was 6.25 ± 0.92 log10 copies per milliliter. After seroconversion, heterogeneity among acute cases was evident by patterns of change in viral load and CD4+ T-cell count over time. The patterns were supported by the rate of viral RNA decline from peak (P = 0.022), viral RNA means (P = 0.005), CD4 levels (P <0.001), and CD4 decline to 350 (P = 0.011) or 200 (P = 0.046). Proviral DNA had no apparent peak and its mean was 2.59 ± 0.69 log10 per 106 peripheral blood mononuclear cell. In recent infections, viral RNA set point was 4.00 ± 0.97 log10 and viral RNA correlated inversely with CD4+ T cells (P <0.001) and directly with proviral DNA (P <0.001).
Distinct patterns of viral RNA evolution may exist shortly after seroconversion in HIV-1 subtype C infection. The study provides better understanding of the early phase of subtype C infection.
PMCID: PMC2701379  PMID: 19295336
acute HIV-1 infection; CD4 count; HIV-1 subtype C; primary HIV-1 infection; natural history; viral load
5.  Risk Factors for Early and Late Transmission of HIV via Breast-Feeding among Infants Born to HIV-Infected Women in a Randomized Clinical Trial in Botswana 
The Journal of infectious diseases  2009;199(3):414-418.
Risk factors for mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) via breast-feeding were evaluated in a randomized trial. HIV-infected women and their infants received zidovudine as well as single-dose nevirapine or placebo. Infants were randomized to formula-feed (FF) or breast-feed (BF) in combination with zidovudine prophylaxis. Of 1116 at-risk infants, 6 (1.1%) in the FF group and 7 (1.3%) in the BF group were infected between birth and 1 month)P = .99). Maternal receipt of nevirapine did not predict early MTCT in the BF group (P = .45). Of 547 infants in the BF group at risk for late MTCT, 24 (4.4%) were infected. Maternal HIV-1 RNA levels in plasma (P<.001) and breast milk (P<.001) predicted late MTCT. These findings support the safety of 1 month of breast-feeding in combination with maternal and infant antiretroviral prophylaxis.
PMCID: PMC2696335  PMID: 19090775

Results 1-5 (5)