Development of a multiassay algorithm (MAA) to identify recent HIV infection in newly diagnosed individuals in Indonesia.

Ongoing HIV transmission is a public health priority in Indonesia. We developed a new multiassay algorithm (MAA) to identify recent HIV infection. The MAA is a sequential decision tree based on multiple biomarkers, starting with CD4+ T cells >200/µL, followed by plasma viral load (pVL) > 1,000 copies/ml, avidity index (AI) < 0 · 7, and pol ambiguity <0 · 47%. Plasma from 140 HIV-infected adults from 19 hospitals across Indonesia (January 2018 - June 2020) was studied, consisting of a training set (N = 60) of longstanding infection (>12-month) and a test set (N = 80) of newly diagnosed (≤1-month) antiretroviral (ARV) drug naive individuals. Ten of eighty (12 · 5%) newly diagnosed individuals were classified as recent infections. Drug resistance mutations (DRMs) against reverse transcriptase inhibitors were identified in two individuals: one infected with HIV subtype C (K219Q, V179T) and the other with CRF01_AE (V179D). Ongoing HIV transmission, including infections with DRMs, is substantial in Indonesia.

Imaging and biopsy of HIV-infected individuals undergoing analytic treatment interruption.

Background: HIV persistence during antiretroviral therapy (ART) is the principal obstacle to cure. Lymphoid tissue is a compartment for HIV, but mechanisms of persistence during ART and viral rebound when ART is interrupted are inadequately understood. Metabolic activity in lymphoid tissue of patients on long-term ART is relatively low, and increases when ART is stopped. Increases in metabolic activity can be detected by 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and may represent sites of HIV replication or immune activation in response to HIV replication. Methods: FDG-PET imaging will be used to identify areas of high and low metabolic uptake in lymphoid tissue of individuals undergoing long-term ART. Baseline tissue samples will be collected. Participants will then be randomized 1:1 to continue or interrupt ART via analytic treatment interruption (ATI). Image-guided biopsy will be repeated 10 days after ATI initiation. After ART restart criteria are met, image-guided biopsy will be repeated once viral suppression is re-achieved. Participants who continued ART will have a second FDG-PET and biopsies 12-16 weeks after the first. Genetic characteristics of HIV populations in areas of high and low FDG uptake will be assesed. Optional assessments of non-lymphoid anatomic compartments may be performed to evaluate HIV populations in distinct anatomic compartments. Anticipated results: We anticipate that PET standardized uptake values (SUV) will correlate with HIV viral RNA in biopsies of those regions and that lymph nodes with high SUV will have more viral RNA than those with low SUV within a patient. Individuals who undergo ATI are expected to have diverse viral populations upon viral rebound in lymphoid tissue. HIV populations in tissues may initially be phylogenetically diverse after ATI, with emergence of dominant viral species (clone) over time in plasma. Dominant viral species may represent the same HIV population seen before ATI. Discussion: This study will allow us to explore utility of PET for identification of HIV infected cells and determine whether high FDG uptake respresents areas of HIV replication, immune activation or both. We will also characterize HIV infected cell populations in different anatomic locations. The protocol will represent a platform to investigate persistence and agents that may target HIV populations. Study protocol registration: Identifier: NCT05419024.

High-level dolutegravir resistance can emerge rapidly from few variants and spread by recombination: implications for integrase strand transfer inhibitor salvage therapy.

The integrase strand transfer inhibitor (INSTI) dolutegravir is commonly used in combination antiretroviral therapy regimens and retains strong potency even with primary resistance mutations to some other INSTIs. Acquisition of accessory mutations to primary mutations results in significant increases in dolutegravir resistance. Previously, we reported that addition of the secondary mutation T97A can result in rapid treatment failure in individuals with INSTI mutations at positions 140 and 148. Here, we conducted a detailed case study of one of these individuals and find that T97A-containing HIV emerged from a large replicating population from only a few (≤4) viral lineages. When combined with primary INSTI resistance mutations, T97A provides a strong selective advantage; the finding that T97A-containing variants spread by replication and recombination, and persisted for months after discontinuing dolutegravir, has important implications as dolutegravir is rolled out worldwide.

Insights into HIV-1 Transmission Dynamics Using Routinely Collected Data in the Mid-Atlantic United States.

Background: Molecular epidemiological approaches provide opportunities to characterize HIV transmission dynamics. We analyzed HIV sequences and virus load (VL) results obtained during routine clinical care, and individual's zip-code location to determine utility of this approach. Methods: HIV-1 pol sequences aligned using ClustalW were subtyped using REGA. A maximum likelihood (ML) tree was generated using IQTree. Transmission clusters with ≤3% genetic distance (GD) and ≥90% bootstrap support were identified using ClusterPicker. We conducted Bayesian analysis using BEAST to confirm transmission clusters. The proportion of nucleotides with ambiguity ≤0.5% was considered indicative of early infection. Descriptive statistics were applied to characterize clusters and group comparisons were performed using chi-square or t-test. Results: Among 2775 adults with data from 2014−2015, 2589 (93%) had subtype B HIV-1, mean age was 44 years (SD 12.7), 66.4% were male, and 25% had nucleotide ambiguity ≤0.5. There were 456 individuals in 193 clusters: 149 dyads, 32 triads, and 12 groups with ≥ four individuals per cluster. More commonly in clusters were males than females, 349 (76.5%) vs. 107 (23.5%), p < 0.0001; younger individuals, 35.3 years (SD 12.1) vs. 44.7 (SD 12.3), p < 0.0001; and those with early HIV-1 infection by nucleotide ambiguity, 202/456 (44.3%) vs. 442/2133 (20.7%), p < 0.0001. Members of 43/193 (22.3%) of clusters included individuals in different jurisdictions. Clusters ≥ four individuals were similarly found using BEAST. HIV-1 viral load (VL) ≥3.0 log10 c/mL was most common among individuals in clusters ≥ four, 18/21, (85.7%) compared to 137/208 (65.8%) in clusters sized 2−3, and 927/1169 (79.3%) who were not in a cluster (p < 0.0001). Discussion: HIV sequence data obtained for HIV clinical management provide insights into regional transmission dynamics. Our findings demonstrate the additional utility of HIV-1 VL data in combination with phylogenetic inferences as an enhanced contact tracing tool to direct HIV treatment and prevention services. Trans-jurisdictional approaches are needed to optimize efforts to end the HIV epidemic.

Corrigendum: A 28-Year History of HIV-1 Drug Resistance and Transmission in Washington, DC.

[This corrects the article DOI: 10.3389/fmicb.2019.00369.].

Transmission Dynamics of HIV Subtype A in Tel Aviv, Israel: Implications for HIV Spread and Eradication.

OBJECTIVE: Subtype-A HIV was introduced into Israel in the mid-1990s, predominantly by immigrants from the former Soviet Union (FSU) infected via intravenous drug use (IVDU). HIV subsequently spread beyond the FSU-IVDU community. In 2012, a mini-HIV outbreak, associated with injection of amphetamine cathinone derivatives, started in Tel Aviv, prompting public health response. To assess current trends and the impact of the outbreak and control measures, we conducted a phyloepidemiologic analysis. METHOD: Demographic and clinical records and HIV sequences were compiled from 312 subtype-A HIV-infected individuals attending the Tel-Aviv Sourasky Medical Center between 2005-2016, where >40% of all subtype-A HIV-infected individuals in Israel are undergoing care. Molecular evolutionary genetics analysis (MEGA) and ayesian evolutionary analysis sampling trees (BEAST) programs were implemented in a phylogenetic analysis of pol sequences. Reconstructed phylogenies were assessed in the context of demographic information and drug-resistance profiles. Clusters were identified as sequence populations with posterior probability ≥0.95 of having a recent common ancestor. RESULTS: After 2010, the subtype-A epidemic acquired substantial phylogenetic structure, having been unrecognized in studies covering the earlier period. Nearly 50% of all sequences were present in 11 distinct clusters consisting of 4-43 individuals. Cluster composition reflected transmission across ethnic groups, with men who have sex with men (MSM) playing an increasing role. The cathinone-associated cluster was larger than previously documented, containing variants that continued to spread within and beyond the IVDU community. CONCLUSIONS: Phyloepidemiologic analysis revealed diverse clusters of HIV infection with MSM having a central role in transmission across ethic groups. A mini outbreak was reduced by public health measures, but molecular evidence of ongoing transmission suggests additional measures are necessary.

A 28-Year History of HIV-1 Drug Resistance and Transmission in Washington, DC.

Washington, DC consistently has one of the highest annual rates of new HIV-1 diagnoses in the United States over the last 10 years. To guide intervention and prevention strategies to combat DC HIV infection, it is helpful to understand HIV transmission dynamics in a historical context. Toward this aim, we conducted a retrospective study (years 1987-2015) of 3,349 HIV pol sequences (1,026 bp) from 1,996 individuals living in the DC area belonging to three different cohorts. We coupled HIV sequence data with clinical information (sex, risk factor, race/ethnicity, viral load, subtype, anti-retroviral regimen) to identify circulating drug resistant mutations (DRM) and transmission clusters and assess their persistence over time. Of the transmission clusters identified in the DC area, 78.0 and 31.7% involved MSM and heterosexuals, respectively. The longest spread of time for a single cluster was 5 years (2007-2012) using a distance-based network inference approach and 27 years (1987-2014) using a maximum likelihood phylogenetic approach. We found eight subtypes and nine recombinants. Genetic diversity increased steadily over time with a slight peak in 2009 and remained constant thereafter until 2015. Nucleotide diversity also increased over time while relative genetic diversity (BEAST) remained relatively steady over the last 28 years with slight increases since 2000 in subtypes B and C. Sequences from individuals on drug therapy contained the highest total number of DRMs (1,104-1,600) and unique DRMs (63-97) and the highest proportion (>20%) of resistant individuals. Heterosexuals (43.94%), MSM (40.13%), and unknown (44.26%) risk factors showed similar prevalence of DRMs, while injection drug users had a lower prevalence (33.33%). Finally, there was a 60% spike in the number of codons with DRMs between 2007 and 2010. Past patterns of HIV transmission and DRM accumulation over time described here will help to predict future efficacy of ART drugs based on DRMs persisting over time and identify risk groups of interest for prevention and intervention efforts within the DC population. Our results show how longitudinal data can help to understand the temporal dynamics of HIV-1 at the local level.

Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir.

HIV integrase mutation T97A emerges after suboptimal therapy with integrase strand transfer inhibitors (INSTIs), but the contribution of T97A to dolutegravir resistance remains uncertain. Here we report >10-fold increase in dolutegravir resistance after the single addition of T97A in 2 individuals with prior INSTI resistance receiving dolutegravir salvage therapy.

Early Presence of HIV-1 Subtype C in Washington, D.C.

The presence of non-B HIV subtypes in the USA has been documented during the epidemic, although the timing of early introductions of different subtypes remains uncertain. Subtype C, the most common HIV variant worldwide, was first reported in the USA in 1996-97, after subtype C had expanded greatly in sub-Saharan Africa. In this study, we report a patient with subtype C infection acquired by mother-to-child transmission, born in the USA in 1990 to a Washington, D.C. resident who never traveled outside the USA, demonstrating that subtype C was present in the USA much earlier. Comparative analysis of the sequence from this patient and subtype C sequences in the USA and elsewhere suggest multiple independent introductions of this subtype into the USA have taken place, many of which are traced to sub-Saharan or East Africa. These data indicate subtype C HIV was already present in the USA years earlier than previously reported, and during the early period of subtype C expansion.

Does parvovirus infection have a role in systemic lupus erythematosus?

We sought to evaluate a possible link between parvovirus B19 infection and the clinical and laboratory expression of systemic lupus erythematosus (SLE). SLE patients were examined to evaluate their clinical status and disease activity. A complete Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was obtained for each patient. In addition, we determined the level of systemic involvement throughout the course of the disease. Blood levels of IgM and IgG antibodies to parvovirus B19, levels of anti-dsDNA, C3, and C4 were measured. A PCR real-time assay was used to determine the presence of parvovirus B19 genetic material. The viral genome was found in sera of 2 of 51(3.9%) patients with SLE. There was no correlation between viral serology and the clinical and serological parameters of the disease. More SLE patients with secondary antiphospholipid syndrome (APS) had IgG and IgM antibodies to the virus (p < 0.029 and p < 0.018, respectively). These patients also had a higher titer of IgG antibodies to parvovirus B19 compared to SLE patients without APS. In this group of SLE patients, no association was found between parvovirus infection and the presence or activity of SLE. The results of the study suggest an association between parvovirus infection and antibody production directed against phospholipids.

Large cluster outbreaks sustain the HIV epidemic among MSM in Quebec.

OBJECTIVE: HIV-1 epidemics among MSM remain unchecked despite advances in treatment and prevention paradigms. This study combined viral phylogenetic and behavioural risk data to better understand underlying factors governing the temporal growth of the HIV epidemic among MSM in Quebec (2002-2015). METHODS: Phylogenetic analysis of pol sequences was used to deduce HIV-1 transmission dynamics (cluster size, size distribution and growth rate) in first genotypes of treatment-naïve MSM (2002-2015, n = 3901). Low sequence diversity of first genotypes (0-0.44% mixed base calls) was used as an indication of early-stage infection. Behavioural risk data were obtained from the Montreal rapid testing site and primary HIV-1-infection cohorts. RESULTS: Phylogenetic analyses uncovered high proportion of clustering of new MSM infections. Overall, 27, 45, 48, 53 and 57% of first genotypes within one (singleton, n = 1359), 2-4 (n = 692), 5-9 (n = 367), 10-19 (n = 405) and 20+ (n = 1277) cluster size groups were early infections (<0.44% diversity). Thirty viruses within large 20+ clusters disproportionately fuelled the epidemic, representing 13, 25 and 42% of infections, first genotyped in 2004-2007 (n = 1314), 2008-2011 (n = 1356) and 2012-2015 (n = 1033), respectively. Of note, 35, 21 and 14% of MSM belonging to 20+, 2-19 and one (singleton) cluster groups were under 30 years of age, respectively. Half of persons seen at the rapid testing site (2009-2011, n = 1781) were untested in the prior year. Poor testing propensity was associated with fewer reported partnerships. CONCLUSION: Addressing the heterogeneity in transmission dynamics among HIV-1-infected MSM populations may help guide testing, treatment and prevention strategies.

Transmitted HIV Drug Resistance Is High and Longstanding in Metropolitan Washington, DC.

BACKGROUND: Washington, DC, has 2.5% human immunodeficiency virus (HIV) prevalence, 3.9% among African Americans. Antiretrovirals (ARTs) are the cornerstone for treatment and prevention. Monitoring changes in transmitted drug resistance (TDR) is critical for effective HIV care. METHODS: HIV genotype data for individuals enrolled in research studies in metropolitan Washington, D.C., were used to identify TDR using the World Health Organization mutation list [Bennett DE, Camacho RJ, Otelea D, et al. Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PloS One 2009; 4:e4724]. HIV phylogenies were reconstructed using maximum likelihood and Bayesian methods. HIV transmission clusters were supported by 1000 bootstrap values >0.70 and posterior probability >0.95 of having a common ancestor. RESULTS: Among 710 individuals enrolled in 1994-2013, the median age was 38.6 years, 46.2% were female, and 53.3% were African-American. TDR was 22.5% among 566 treatment-naive individuals; 15.8% had nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance, 9.8% had nonnucleoside reverse-transcriptase inhibitor (NNRTI) resistance, and 4.2% had protease inhibitor (PI) resistance. Single class TDR was 10.0%, 5.1%, and 1.6% to NRTIs, NNRTIs, and PIs. Dual TDR to PI and NRTI was seen in 1.6%, NRTI and NNRTI in 3.4%, and triple class TDR in 0.9%. TDR frequency decreased from 1994-2006 (27.1%) to 2007-2013 (19.4%; P = .02). Only 6/79 (7.6%) individuals within transmission clusters had evidence of TDR. DISCUSSIONS: We identified high prevalence of TDR among HIV-infected individuals in metropolitan Washington, DC, regardless of gender. Active surveillance for TDR is needed to guide ART usage and analyses of risk group contributions to HIV transmission and resistance.

The global spread of HIV-1 subtype B epidemic.

Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood. Here we analyze a large dataset of globally representative HIV-1 subtype B strains to map their spread around the world over the last 50years and describe significant spread patterns. We show that subtype B travelled from North America to Western Europe in different occasions, while Central/Eastern Europe remained isolated for the most part of the early epidemic. Looking with more detail in European countries we see that the United Kingdom, France and Switzerland exchanged viral isolates with non-European countries than with European ones. The observed pattern is likely to mirror geopolitical landmarks in the post-World War II era, namely the rise and the fall of the Iron Curtain and the European colonialism. In conclusion, HIV-1 spread through specific migration routes which are consistent with geopolitical factors that affected human activities during the last 50years, such as migration, tourism and trade. Our findings support the argument that epidemic control policies should be global and incorporate political and socioeconomic factors.

Characteristics and Outcome of Patients Diagnosed With HIV at Older Age.

To characterize the clinical, virological, and immunological status at presentation as well as the outcome of patients diagnosed with HIV above the age of 50. A retrospective study of 418 patients newly diagnosed with HIV in 1 Israeli center, between the years 2004 and 2013. Patients with new HIV diagnosis ≥ 50 years of age defined as "older' and < 50 defined as "younger.' Patients were evaluated every 1 to 3 months (mean follow-up 53 ± 33 months). Patients with < 2 CD4/viral-load measurements or with < 1 year of follow-up were excluded. Time of HIV infection was estimated by HIV sequence ambiguity assay. Ambiguity index ≤ 0.43 indicated recent (≤ 1 year) HIV infection. Eighty nine (21%) patients were diagnosed with HIV at an older age. Those older patients presented with significant lower CD4 cell counts and higher viral-load compared with the younger patients. At the end of the study, the older patients had higher mortality rate (21% vs 3.5%; P < 0.001) and lower CD4 cell counts (381 ± 228 vs 483 ± 26 cells/µL; P < 0.001) compared with the younger patients. This difference was also observed between older and younger patients with similar CD4 cell counts and viral load at the time of HIV diagnosis and among patients with a recent (≤ 1 year) HIV infection. One-fifth of HIV patients are diagnosed at older age (≥ 50 years). Those older patients have less favorable outcome compared with the younger patients. This point to the need of educational and screening programs within older populations and for a closer follow-up of older HIV patients.

A Population-Structured HIV Epidemic in Israel: Roles of Risk and Ethnicity.

BACKGROUND: HIV in Israel started with a subtype-B epidemic among men who have sex with men, followed in the 1980s and 1990s by introductions of subtype C from Ethiopia (predominantly acquired by heterosexual transmission) and subtype A from the former Soviet Union (FSU, most often acquired by intravenous drug use). The epidemic matured over the last 15 years without additional large influx of exogenous infections. Between 2005 and 2013 the number of infected men who have sex with men (MSM) increased 2.9-fold, compared to 1.6-fold and 1.3-fold for intravenous drug users (IVDU) and Ethiopian-origin residents. Understanding contemporary spread is essential for effective public health planning. METHODS: We analyzed demographic and virologic data from 1,427 HIV-infected individuals diagnosed with HIV-I during 1998-2012. HIV phylogenies were reconstructed with maximum-likelihood and Bayesian methods. RESULTS: Subtype-B viruses, but not A or C, demonstrated a striking number of large clusters with common ancestors having posterior probability ≥0.95, including some suggesting presence of transmission networks. Transmitted drug resistance was highest in subtype B (13%). MSM represented a frequent risk factor in cross-ethnic transmission, demonstrated by the presence of Israeli-born with non-B virus infections and FSU immigrants with non-A subtypes. CONCLUSIONS: Reconstructed phylogenetic trees demonstrated substantial grouping in subtype B, but not in non-MSM subtype-A or in subtype-C, reflecting differences in transmission dynamics linked to HIV transmission categories. Cross-ethnic spread occurred through multiple independent introductions, with MSM playing a prevalent role in the transmission of the virus. Such data provide a baseline to track epidemic trends and will be useful in informing and quantifying efforts to reduce HIV transmission.

Global Dispersal Pattern of HIV Type 1 Subtype CRF01_AE: A Genetic Trace of Human Mobility Related to Heterosexual Sexual Activities Centralized in Southeast Asia.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) subtype CRF01_AE originated in Africa and then passed to Thailand, where it established a major epidemic. Despite the global presence of CRF01_AE, little is known about its subsequent dispersal pattern. METHODS: We assembled a global data set of 2736 CRF01_AE sequences by pooling sequences from public databases and patient-cohort studies. We estimated viral dispersal patterns, using statistical phylogeographic analysis run over bootstrap trees estimated by the maximum likelihood method. RESULTS: We show that Thailand has been the source of viral dispersal to most areas worldwide, including 17 of 20 sampled countries in Europe. Japan, Singapore, Vietnam, and other Asian countries have played a secondary role in the viral dissemination. In contrast, China and Taiwan have mainly imported strains from neighboring Asian countries, North America, and Africa without any significant viral exportation. DISCUSSION: The central role of Thailand in the global spread of CRF01_AE can be probably explained by the popularity of Thailand as a vacation destination characterized by sex tourism and by Thai emigration to the Western world. Our study highlights the unique case of CRF01_AE, the only globally distributed non-B clade whose global dispersal did not originate in Africa.

Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe.

BACKGROUND: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program. METHODS: Clinical, epidemiological and virological data from 4317 patients newly diagnosed with HIV-1 infection between 2002 and 2007 were analysed. Patients were enrolled using a pre-defined sampling strategy. RESULTS: The overall prevalence of TDRM in this period was 8.9% (95% CI: 8.1-9.8). Interestingly, significant changes over time in TDRM caused by the different drug classes were found. Whereas nucleoside resistance mutations remained constant at 5%, a significant decline in protease inhibitors resistance mutations was observed, from 3.9% in 2002 to 1.6% in 2007 (p = 0.001). In contrast, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) doubled from 2.0% in 2002 to 4.1% in 2007 (p = 0.004) with 58% of viral strains carrying a K103N mutation. Phylogenetic analysis showed that these temporal changes could not be explained by large clusters of TDRM. CONCLUSION: During the years 2002 to 2007 transmitted resistance to NNRTI has doubled to 4% in Europe. The frequent use of NNRTI in first-line regimens and the clinical impact of NNRTI mutations warrants continued monitoring.

Patterns of transmitted HIV drug resistance in Europe vary by risk group.

BACKGROUND: In Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported. METHODS: HIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression. RESULTS: From the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more often from Western Europe origin, infected with subtype B virus, and recently infected (<1 year) (p<0.001). The prevalence of TDRM was highest in MSM (prevalence of 11.1%), followed by heterosexuals (6.6%) and IDU (5.1%, p<0.001). TDRM was predominantly ascribed to nucleoside reverse transcriptase inhibitors (NRTI) with a prevalence of 6.6% in MSM, 3.3% in heterosexuals and 2.0% in IDU (p = 0.001). A significant increase in resistance to non- nucleoside reverse transcriptase inhibitors (NNRTIs) and a decrease in resistance to protease inhibitors was observed in MSM (p = 0.008 and p = 0.006, respectively), but not in heterosexual patients (p = 0.68 and p = 0.14, respectively). CONCLUSIONS: MSM showed to have significantly higher TDRM prevalence compared to heterosexuals and IDU. The increasing NNRTI resistance in MSM is likely to negatively influence the therapy response of first-line therapy, as most include NNRTI drugs.

Comparable long-term efficacy of Lopinavir/Ritonavir and similar drug-resistance profiles in different HIV-1 subtypes.

BACKGROUND: Analysis of potentially different impact of Lopinavir/Ritonavir (LPV/r) on non-B subtypes is confounded by dissimilarities in the conditions existing in different countries. We retrospectively compared its impact on populations infected with subtypes B and C in Israel, where patients infected with different subtypes receive the same treatment. METHODS: Clinical and demographic data were reported by physicians. Resistance was tested after treatment failure. Statistical analyses were conducted using SPSS. RESULTS: 607 LPV/r treated patients (365 male) were included. 139 had HIV subtype B, 391 C, and 77 other subtypes. At study end 429 (71%) were receiving LPV/r. No significant differences in PI treatment history and in median viral-load (VL) at treatment initiation and termination existed between subtypes. MSM discontinued LPV/r more often than others even when the virologic outcome was good (p = 0.001). VL was below detection level in 81% of patients for whom LPV/r was first PI and in 67% when it was second (P = 0.001). Median VL decrease from baseline was 1.9±0.1 logs and was not significantly associated with subtype. Median CD4 increase was: 162 and 92cells/µl, respectively, for patients receiving LPV/r as first and second PI (P = 0.001), and 175 and 98, respectively, for subtypes B and C (P<0.001). Only 52 (22%) of 237 patients genotyped while under LPV/r were fully resistant to the drug; 12(5%) were partially resistant. In48%, population sequencing did not reveal resistance to any drug notwithstanding the virologic failure. No difference was found in the rates of resistance development between B and C (p = 0.16). CONCLUSIONS: Treatment with LPV/r appeared efficient and tolerable in both subtypes, B and C, but CD4 recovery was significantly better in virologically suppressed subtype-B patients. In both subtypes, LPV/r was more beneficial when given as first PI. Mostly, reasons other than resistance development caused discontinuation of treatment.

[HIV testing: the medical laboratory role in HIV diagnosis and monitoring].

Diagnosis of HIV infection is performed via enzyme immunoassay (EIA), an assay based on screening for antibodies against HIV. Confirmation of diagnosis is performed by Western-Blot, a more specific assay directed at a number of viral proteins for which antibodies exist. Routine follow-up of HIV-infected individuals includes measurement of CD4 cell count to evaluate the immune status, of viral load to assess virus replication, and of changes in the viral genome to characterize resistance to drugs and tropism. In addition, absence of the HLA B*57:01 allele is verified before prescription of abacavir, and drug levels of protease-inhibitors are determined in treatment-failing individuals after ruling out other causes of failure. Rapid diagnosis and regular follow-up improve the quality of life of patients and extend their life expectancy, also helping to control the spread of the epidemic at the national level.