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Proposes three HTLV-IIa phylogroups and four HTLV-IIb phylogroups culled from phylogenetic analysis of long terminal repeat (LTR) sequences from 29 HTLV-II strains from endemic and nonendemic populations. Sequences from American and European intravenous drug users; Clustering of sequences from an African Pygmy and Seminole and Pueblo Indians and other non-Indian American samples.

Objective: To estimate time of HIV infection in participants from the Bangkok Tenofovir Study (BTS) with daily oral tenofovir disoproxil fumarate (TDF) for preexposure prophylaxis (PrEP) and relate infection with adherence patterns., Design: We used the diversity structure of the virus population at the first HIV RNA-positive sample to estimate the date of infection, and mapped these estimates to medication diaries obtained under daily directly observed therapy (DOT)., Methods: HIV genetic diversity was investigated in all 17 PrEP breakthrough infections and in 16 placebo recipients. We generated 10-25 HIV env sequences from each participant by single genome amplification, and calculated time since infection (and 95% confidence interval) using Poisson models of early virus evolution. Study medication diaries obtained under daily DOT were then used to compute the number of missed TDF doses at the approximate date of infection., Results: Fifteen of the 17 PrEP breakthrough infections were successfully amplified. Of these, 13 were initiated by a single genetic variant and generated reliable estimates of time since infection (median = 47 [IQR = 35] days). Eleven of these 13 were under daily DOT at the estimated time of infection. Analysis of medication diaries in these 11 participants showed 100% adherence in five, 90-95% adherence in two, 55% adherence in one, and nonadherence in three., Conclusion: We estimated time of infection in participants from BTS and found several infections when high levels of adherence to TDF were reported. Our results suggest that the biological efficacy of daily TDF against parenteral HIV exposure is not 100%.

Objective: To examine the association of majority and minority-level transmitted HIV drug resistance (TDR) among diverse demographic populations in the United States and assess what different mutations may infer about TDR risk and engagement in care., Design: Used sensitive assays to screen 1070 deidentified convenience plasma specimens from United States national HIV surveillance conducted in 2009-2011 on newly diagnosed persons with no evidence of antiretroviral drug use., Methods: We applied validated allele-specific PCR for five HIV reverse transcriptase mutations as sentinel markers of TDR. The total and minority-level prevalence of TDR by demographic characteristics was compared., Results: Sensitive screening identified 72% more TDR than conventional sequencing for the five mutations assessed (13.6 vs. 7.9%, P < 0.0001), with K65R having the greatest increase (0-1.7%). One-third of K65R was in persons who also had at least one of the other mutations screened. The total TDR prevalence among whites (16.4%) and blacks (14.9%) was significantly higher than that among Hispanics/Latinos (6.4%) (P = 0.005 and 0.013, respectively). TDR prevalence was highest (23.1%) in those 13-19 years (85% black). TDR prevalence among women (72% black) was nearly as high as among MSM (47% black) (14.3 vs. 15.1%, respectively)., Conclusion: A significant proportion of TDR, primarily in older, white MSM, was undetected by conventional testing. The greatest underestimation was for rapid-decaying mutations typically associated with the source virus having recent exposure to antiretroviral therapy. However, total TDR prevalence was highest in the less than 20-year age group who were predominantly black, underscoring the importance of prevention efforts for at-risk youth.

Objective: To determine the distribution of HIV-1 subtypes and the prevalence of transmitted drug resistance-associated mutations (TDRM) among persons newly diagnosed with HIV-1 infection in the United States., Methods: We used sequence data from Variant, Atypical, and Resistant HIV Surveillance (VARHS) collected from newly diagnosed persons in 10 states and 1 county health department in 2006. To evaluate TDRM, we used a mutation list for surveillance of TDRM appropriate for the primarily subtype B HIV epidemic in the United States., Results: Sequences were obtained from 2030 of 10,860 persons newly diagnosed with HIV in 11 surveillance areas. Mutations associated with transmitted drug resistance occurred in 292 (14.6%) persons; TDRM associated with a specific drug class occurred in 156 (7.8%) for non-nucleoside reverse transcriptase inhibitors, 111 (5.6%) for nucleoside reverse transcriptase inhibitors and 90 (4.5%) for protease inhibitors. There were no significant differences in prevalence of TDRM by demographic characteristic. The HIV-1 subtype B was the most prevalent subtype occurring in 1922 (96.2%) persons; subtype C (1.3%) was the most prevalent non-B subtype., Conclusion: We presented a clade B-optimized mutation list for evaluating surveillance of TDRM in the United States and analyzed the largest collection of sequence data obtained from individuals newly diagnosed with HIV. The prevalence of TDRM in persons newly diagnosed with HIV is higher than in previous U.S. studies; however, this is not necessarily a significant trend. Continued reporting of sequence data for public health purposes from all sources will improve representativeness and accuracy in analyzing trends in transmitted drug resistance and genetic diversity.

Objective: To assess the impact of prior exposure to single-dose nevirapine (sdNVP) on mother-to-child transmission and genotypic resistance in HIV-infected women., Design: Prospective study of 120 women exposed to the HIVNET 012 sdNVP regimen in two successive pregnancies and 240 antiretroviral (ARV)-naïve, multiparous women who received sdNVP for the first time., Results: One hundred and eight of 120 and 193 of 240 women returned for a postpartum visit by 6 weeks. HIV-1 was detected in 11.1% (95% confidence interval = 5.9-18.6) of the infants of women previously exposed to sdNVP and 4.2% (95% confidence interval = 1.3-7.0) of those exposed for the first time (P = 0.028). Rates of maternal HIV-1 genotypic resistance at 6 weeks postdelivery were 37.5% and 46.4%, respectively (P = 0.119). Sensitive mutation-specific real-time PCR testing found three of 12 previously exposed women who transmitted HIV-1 to their infants had either K103N or Y181C at baseline compared with one of eight ARV-naïve, transmitting women who had Y181C. None of 40 randomly selected nontransmitting women from either group had detectable NVP resistance mutations prior to sdNVP exposure., Conclusion: This study shows that effectiveness of sdNVP may be compromised by prior exposure to sdNVP, although the increase in transmission rate after prior exposure could not be explained by the detection of NVP resistance mutations prior to re-exposure as measured both by standard genotyping and highly sensitive allele-specific PCR assays. Furthermore, transmission rates of women with prior exposure were not higher than those reported elsewhere.

Objective: Dried blood spots (DBS) are a convenient alternative to plasma for drug resistance testing in resource-limited settings. We investigated the correlation between resistance genotypes generated from DBS and plasma., Design: Sixty DBS specimens from HIV-1 subtype B-infected antiretroviral-experienced (n = 58) and naive patients (n = 2) were tested. DBS were prepared using 50 mul blood and were stored with desiccant at -20 degrees C., Methods: Resistance genotypes from DBS were obtained using the ViroSeq HIV-1 assay and were compared with genotypes derived from plasma. The frequency of amplification of proviral DNA from DBS was evaluated using an in-house nested polymerase chain reaction assay., Results: : Fifty of the 60 DBS specimens were successfully genotyped including all 38 specimens collected from patients with plasma viral loads greater than 2000 copies/ml and 12 of 22 DBS (54.5%) from patients with viral loads less than 2000 copies/ml. HIV-1 DNA was detected in 44.4% of the DBS. Despite the presence of DNA, genotypes from DBS and plasma were highly concordant. Of the 316 mutations found in plasma sequences, 306 (96.8%) were also found in DBS. Discrepancies were mostly caused by mixtures at minor protease positions or unusual amino acid changes, and in only two cases were caused by major protease (M46L) or reverse transcriptase (K103N) mutations absent in DBS sequences., Conclusion: : We demonstrated a high concordance between resistance genotypes from plasma and DBS, and that resistance testing from DBS can achieve sensitive levels similar to those seen using plasma. Our results indicate that DBS may represent a feasible alternative to plasma for drug resistance testing in treated individuals.

Background: Xenotransplantation offers a solution to the shortage of organ donors and may offer resistance to human-specific pathogens. Baboons are resistant to productive infection with HIV-1. A baboon bone-marrow transplant (BMT) was performed in an attempt to reconstitute the immune system of a patient with advanced AIDS. The aims of this pilot study were to evaluate the safety of the procedure and develop an approach to prevent and monitor for xenozoonoses., Methods: A source animal was selected on the basis of infectious disease surveillance protocols. Baboon bone marrow, engineered to remove graft-versus-host-disease-producing mature lineages, but to retain hematopoietic stem cells and facilitating cells, was infused into the patient after nonmyeloablative conditioning. Serial clinical, virologic, immunologic, and hematologic evaluations were performed., Results: A 38-year-old male with advanced AIDS, who had failed to respond to triple-drug antiretroviral therapy, underwent baboon BMT in 1995. The patient tolerated the procedure without complication. Baboon cells were detected in the peripheral blood on days 5 and 13 after transplantation. Baboon endogenous virus (BaEV) was detected on day 5 but not subsequently. Antibody to BaEV was not detected. HIV-1 viral load declined 1.5 log and remained low until 11 months. The patient improved clinically, and no adverse events occurred. The patient is alive 8 years after the procedure., Conclusions: Baboon BMT to treat AIDS was attempted using nonmyeloablative conditioning and resulted in transient microchimerism and clinical and virologic improvements. Long-term improvement was not achieved; however, no adverse events occurred, and no evidence of transmission of xenogeneic infections was found.

Background: HIV-1 protease inhibitors (PI) have been used for treating HIV-2-infected persons but little is known about amino acid mutations associated with PI resistance in HIV-2 and whether they are similar to those seen in HIV-1., Objective: To determine the frequency of HIV-1 PI resistance-associated mutations in PI-naive HIV-2-infected individuals., Design: Using PCR, protease genes were amplified from 76 individuals, directly sequenced, phylogenetically subtyped, and translated into amino acids to analyze PI-associated major and minor mutations., Results: Of the 76 HIV-2 sequences, 68% belonged to subtype A and 32% to subtype B. All sequences contained at least four codon changes giving substitutions at 10, 30, 32, 36, 46, 47, 71 or 77. The frequency of these mutations was similar in subtype A and B viruses. Two major resistance-conferring mutations, 30N and 46I, were identified in one (1%) and 68 (89%) specimens, respectively. Minor mutations 10V/I, 32I, 36I, 47V, and 71V were predominant (89%-100%), followed by the rare mutation 77I (1%). Of the 76 strains, 89% harbored multiple PI resistance-associated substitutions comprising both the major 46I and minor mutations: 10V/I, 32I, 36I, 46I, 47V, 71V (76%); 10V, 32I, 36I, 46I, 47V (9%); and 10V, 32I, 36I, 46I, 47V 71V, 77I (1.3%), 10V, 32I, 46I, 47V, 71V (1.3%), and 10V, 30N, 32I, 36I, 46I, 47V, 71V (1.3%). The remaining 11% of the sequences had patterns with only minor mutations: 10V, 32I, 36I, 47V, 71V (9%) and 10V, 32I, 36I, 47V (1.3%)., Conclusions: The high frequency of multiple PI-associated substitutions represent natural polymorphisms occurring in HIV-2 strains of subtypes A and B. Phenotypic and clinical studies are needed to determine the relevance of these substitutions.

Objective: To describe changes in plasma viral load, CD4+ cell counts, and drug resistance profiles of HIV-2-infected patients receiving antiretroviral (ARV) therapy in Abidjan, Côte d'Ivoire., Methods: Consecutive blood samples were collected from 18 HIV-2-infected ARV-naive patients who had received ARV therapy in the UNAIDS drug access initiative (UNAIDS-DAI) in Abidjan between August 1998 and July 2000. Changes in HIV-2 plasma viral load, CD4+ cell counts, and genotypic and phenotypic drug resistance testing were determined., Results: At baseline, 11 (61%) of the 18 patients initiated highly active antiretroviral therapy (HAART) and seven (39%) received dual therapy. No significant change in median viral load was observed at 2 months (P = 0.09), at 6 months (P = 0.06), and at 12 months of therapy (P = 0.26). No significant increase in CD4+ cell counts was observed at 12 months (P = 0.10). All four patients on indinavir-containing HAART had undetectable viral loads at 2-4 months of therapy. However, none of seven patients on nelfinavir-containing HAART had a substantial decrease in viral load. Viruses from 14 patients were analyzed, 12 of which (86%) had at least one primary resistance mutation that is known to confer resistance to HIV-1 virus. Three patients had the multi-drug-resistant mutation, Q151M, two of whom showed reduced susceptibility to zidovudine, didanosine, stavudine and zalcitabine., Conclusion: Our limited findings show that nelfinavir-containing regimens may have limited virologic benefit to HIV-2-infected patients.