Tracing the origin and dynamics of the HIV-1 epidemic in Serbia

Since the first report of HIV infection in Serbia in 1985, the HIV-1 epidemic was very dynamic, changing the pattern in subtype distribution and prevailing transmission routes. To better understand the origin and epidemiological dynamics of HIV-1, we analyzed 266 (pol) sequences from Serbian patients diagnosed over a period of 14 years. Subtype distribution in Serbia is still marked by a prevailing subtype B genetic form. The transmission pattern, however, has changed from being intravenous drug user (IVDU) - driven to predominantly sexual transmission. The estimated time of initial founder strain introduction of sequences from Serbian IVDUs and MSM (men who have sex with men) is similar and dates back to the early 1980s, while introduction of subtype C occurred much more recently.

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Prevalence of different HIV-1 subtypes in sexual transmission in China: a systematic review and meta-analysis

Epidemiology and Infection ◽

10.1017/s0950268816000212 ◽

2016 ◽

Vol 144 (10) ◽

pp. 2144-2153 ◽

Cited By ~ 16

Author(s):

R. YUAN ◽

H. CHENG ◽

L.-S. CHEN ◽

X. ZHANG ◽

B. WANG

Keyword(s):

Hiv Transmission ◽

Meta Analysis ◽

Sexual Transmission ◽

Heterosexual Transmission ◽

Subtype C ◽

Comprehensive Overview ◽

Subtype B ◽

Pooled Prevalence ◽

Hiv 1 ◽

Subtype Distribution

SUMMARYSexual transmission has become the primary route of HIV transmission in China. Therefore, a comprehensive overview of HIV-1 subtype distribution is necessary for the prevention and control of the HIV epidemic. The present study aimed to provide a comprehensive prevalence estimate of different HIV-1 subtypes in sexual transmission in China. We conducted a systematic literature review for studies of HIV-1 subtypes in English and Chinese through several databases. Eligible articles were screened and selected by two authors independently. Random-effects model were applied to calculate the pooled prevalence of different HIV-1 subtypes, and subgroup analyses examined prevalence estimates across time, locations, and populations. A total of 130 eligible studies were identified, including 18 752 successfully genotyped samples. The pooled prevalence of CRF01_AE, subtype B, CRF07_BC, CRF08_BC, and subtype C were 44·54% (95% CI 40·81–48·30), 18·31% (95% CI 14·71–22·17), 16·45% (95% CI 13·82–19·25), 2·55% (95% CI 1·56–3·73), 0·37% (95% CI 0·11–0·72), respectively. The prevalence of subtype B in sexual transmission decreased, while the prevalence of CRF01_AE and CRF07_BC in sexual transmission, and CRF08_BC in heterosexual transmission increased. There is significant variation in HIV-1 subtype distribution between regions. The distribution of HIV-1 subtypes and circulating recombinant forms have changed significantly. The high genetic variability of HIV-1 poses a significant challenge for disease control and surveillance in China.

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Increase in HIV-1-transmitted drug resistance among ART-naïve youths at the China-Myanmar border during 2009 ~ 2017

BMC Infectious Diseases ◽

10.1186/s12879-021-05794-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yibo Ding ◽

Min Chen ◽

Jibao Wang ◽

Yuecheng Yang ◽

Yi Feng ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Cd4 Count ◽

Transmitted Drug Resistance ◽

Subtype C ◽

Reverse Transcriptase Inhibitors ◽

Recombination Hotspots ◽

Subtype B ◽

Sex With Men ◽

Hiv 1

Abstract Background HIV-transmitted drug resistance (TDR) is found in antiretroviral therapy (ART)-naïve populations infected with HIV-1 with TDR mutations and is important for guiding future first- and second-line ART regimens. We investigated TDR and its effect on CD4 count in ART-naïve youths from the China-Myanmar border near the Golden Triangle to better understand TDR and effectively guide ART. Methods From 2009 to 2017, 10,832 HIV-1 infected individuals were newly reported along the Dehong border of China, 573 ART-naïve youths (16 ~ 25 y) were enrolled. CD4 counts were obtained from whole blood samples. HIV pol gene sequences were amplified from RNA extracted from plasma. The Stanford REGA program and jpHMM recombination prediction tool were used to determine genotypes. TDR mutations (TDRMs) were analyzed using the Stanford Calibrated Population Resistance tool. Results The most common infection route was heterosexuals (70.51%), followed by people who inject drugs (PWID, 19.20%) and men who have sex with men (MSM) (8.90%). The distribution of HIV genotypes mainly included the unique recombinant form (URF) (44.08%), 38.68% were CRFs, 13.24% were subtype C and 4.04% were subtype B. The prevalence of TDR increased significantly from 2009 to 2017 (3.48 to 9.48%) in ART-naïve youths (4.00 to 13.16% in Burmese subjects, 3.33 to 5.93% in Chinese subjects), and the resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 3.49, 2.62, and 0.52%, respectively. Most (94.40%, n = 34) of HIV-1-infected patients with TDRM had mutation that conferred resistance to a single drug class. The most common mutations Y181I/C and K103N, were found in 7 and 9 youths, respectively. The mean CD4 count was significantly lower among individuals with TDRMs (373/mm3 vs. 496/mm3, p = 0.013). Conclusions The increase in the prevalence of HIV-1 TDR increase and a low CD4 count of patients with TDRMs in the China-Myanmar border suggests the need for considering drug resistance before initiating ART in HIV recombination hotspots.

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Intrasubtype B HIV-1 Superinfection Correlates with Delayed Neutralizing Antibody Response

Journal of Virology ◽

10.1128/jvi.00475-17 ◽

2017 ◽

Vol 91 (17) ◽

Cited By ~ 7

Author(s):

Gabriel A. Wagner ◽

Elise Landais ◽

Gemma Caballero ◽

Pham Phung ◽

Sergei L. Kosakovsky Pond ◽

...

Keyword(s):

Antibody Response ◽

Hiv Infection ◽

Primary Infection ◽

Natural Infection ◽

Neutralizing Antibody ◽

Correlates Of Protection ◽

Subtype B ◽

Tier 1 ◽

Sex With Men ◽

Hiv 1

ABSTRACT Understanding whether the neutralizing antibody (NAb) response impacts HIV-1 superinfection and how superinfection subsequently modulates the NAb response can help clarify correlates of protection from HIV exposures and better delineate pathways of NAb development. We examined associations between the development of NAb and the occurrence of superinfection in a well-characterized, antiretroviral therapy (ART)-naive, primary infection cohort of men who have sex with men. Deep sequencing was applied to blood plasma samples from the cohort to detect cases of superinfection. We compared the NAb activity against autologous and heterologous viruses between 10 participants with intrasubtype B superinfection and 19 monoinfected controls, matched to duration of infection and risk behavior. Three to 6 months after primary infection, individuals who would later become superinfected had significantly weaker NAb activity against tier 1 subtype B viruses (P = 0.003 for SF-162 and P = 0.017 for NL4-3) and marginally against autologous virus (P = 0.054). Lower presuperinfection NAb responses correlated with weaker gp120 binding and lower plasma total IgG titers. Soon after superinfection, the NAb response remained lower, but between 2 and 3 years after primary infection, NAb levels strengthened and reached those of controls. Superinfecting viruses were typically not susceptible to neutralization by presuperinfection plasma. These observations suggest that recently infected individuals with a delayed NAb response against primary infecting and tier 1 subtype B viruses are more susceptible to superinfection. IMPORTANCE Our findings suggest that within the first year after HIV infection, a relatively weak neutralizing antibody response against primary and subtype-specific neutralization-sensitive viruses increases susceptibility to superinfection in the face of repeated exposures. As natural infection progresses, the immune response strengthens significantly in some superinfected individuals. These findings will inform HIV vaccine design by providing testable correlates of protection from initial HIV infection.

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Prevalence of Different Genotypes of HIV-1 in Injection Drug Users in China: A Systematic Review and Meta-Analysis

Current HIV Research ◽

10.2174/1570162x17666190919115036 ◽

2019 ◽

Vol 17 (4) ◽

pp. 240-257

Author(s):

Yu Jiang ◽

Lincai Zhang ◽

Zongjie Hou ◽

Aixia Tu ◽

Ruijuan Qiao ◽

...

Keyword(s):

Systematic Review ◽

Injection Drug Users ◽

Drug Users ◽

Meta Analysis ◽

Sexual Transmission ◽

Injection Drug ◽

Subtype C ◽

Subtype B ◽

Prevalent Strain ◽

Hiv 1

Background: Since 1981, an increasing trend in HIV has been observed for transmission via injection drug users (IDUs), sexual transmission and mother-to-child transmission. The IDUs are blamed for early increases in HIV-positive cases in China. Objective: HIV genotypes of IDUs were comprehensively analysed to trace the source and relationships of the AIDS epidemic in China. Methods: Relevant databases written in English and Chinese were searched. Overall, 7,149 publications were identified in six databases. After screening 7,104 articles according to the inclusion and exclusion criteria, 45 studies consisting of 2,765 cases were finally identified. A meta-analysis was conducted using R MATLAB software, RevMan and SPSS. Subgroup analyses focused on time frame, region, and location of different genotypes of IDUs in China. Results: There were five dominant HIV-1 genotypes among the 2,765 IDU cases. The proportions of CRF07_BC, CRF01_AE, CRF08_BC, subtype B/B', and subtype C were 45.18% (95% CI: 33.55-57.08%), 16.00% (95% CI: 9.39-23.82%), 13.43% (95% CI: 7.32-20.84%), 3.58% (95% CI: 1.52-6.24%), and 0.90% (95% CI: 0.04-2.43%), respectively. HIV genotypes transmitted among IDUs in China are primarily CRF07-BC, followed by CRF01-AE and CRF08-BC. Across the different time frames and regions, CRF07_BC was the most prevalent HIV-1 genotype among IDUs, while CRF08_BC was the most prevalent genotype in the southwest region. Conclusion: Our study reveals that CRF07-BC was the dominant prevalent strain among IDUs from 1991 to 2015 in China, while CRF08-BC was the dominant prevalent strain among IDUs in southwestern China. This systematic review and meta-analysis shows evidence of the comprehensive prevalence of different genotypes, data and characteristics of HIV among IDUs in China.

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Molecular Characterization of HIV-1 Minority Subtypes in Hong Kong: A Recent Epidemic of CRF07_BC among the Men who have Sex with Men Population

Current HIV Research ◽

10.2174/1570162x17666190530081355 ◽

2019 ◽

Vol 17 (1) ◽

pp. 53-64 ◽

Cited By ~ 2

Author(s):

Kenneth Siu-Sing Leung ◽

Sabrina Wai-Chi To ◽

Jonathan Hon-Kwan Chen ◽

Gilman Kit-Hang Siu ◽

Kenny Chi-Wai Chan ◽

...

Keyword(s):

Phylogenetic Analysis ◽

Hong Kong ◽

Risk Groups ◽

Transmission Risk ◽

Surveillance Program ◽

Subtype C ◽

Subtype B ◽

Potential Association ◽

Sex With Men ◽

Hiv 1

Background: Over the past years, an increasing trend was noticed for non-B and non- CRF01_AE HIV-1 strains prevalence in Hong Kong. Objective: In this study, we aimed at using the available HIV-1 pol sequences collected from 1994 to 2013 through our local antiretroviral resistance surveillance program to investigate the molecular epidemiology and evolution of HIV-1 minority subtypes in Hong Kong. We also aimed at investigating their potential association and impact of those transmission risk groups. Methods: A total of 2,315 HIV-1 partial pol sequences were included. HIV-1 genotypes were determined by REGA Genotyping Tool and phylogenetic analysis with reference sequences. The viral evolutionary rates and time of the most common ancestor (tMRCA) were estimated by Bayesian Markov Chain Monte Carlo (MCMC) interference. Results: Apart from the two prevalent HIV-1 genotypes in Hong Kong (subtype B,41.6%, CRF01_AE,40.5%), phylogenetic analysis revealed a broad viral diversity including CRF07_BC(5.1%), subtype C(4.5%), CRF02_AG(1.1%), CRF08_BC(0.8%), subtype A1(0.8%), subtype G(0.4%), subtype D(0.4%), CRF06_cpx(0.4%), subtype F(0.1%), CRF12_BF(0·04%) and other recombinants(4.5%). The top five minority subtypes were further analyzed which demonstrated distinct epidemiological and phylogenetic patterns. Over 70% of subtypes A1, C and CRF02_AG infections were circulated among non-Chinese Asians or African community in Hong Kong and were mainly transmitted between heterosexual regular partners. Instead, over 90% of CRF07_BC and CRF08_BC patients were Chinese. An epidemic cluster was identified in CRF07_BC and estimated to expand from 2002 onwards based on skyline plot and molecular clock analysis. Conclusion: Our results highlighted the emergence of CRF07_BC epidemic in local MSM community, public health interventions targeting the community should be further enhanced to tackle the epidemic.

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Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil

International Journal of Molecular Sciences ◽

10.3390/ijms22105304 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5304

Author(s):

Ana Santos-Pereira ◽

Vera Triunfante ◽

Pedro M. M. Araújo ◽

Joana Martins ◽

Helena Soares ◽

...

Keyword(s):

Drug Resistance ◽

People Living With Hiv ◽

Resistance Mutations ◽

Subtype C ◽

Viral Loads ◽

Drug Resistance Mutations ◽

Subtype B ◽

Low Prevalence ◽

Living With Hiv ◽

Hiv 1

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008–2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.

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Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018

BMC Infectious Diseases ◽

10.1186/s12879-021-06312-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhen Wang ◽

Bin Zhao ◽

Minghui An ◽

Wei Song ◽

Xue Dong ◽

...

Keyword(s):

Drug Resistance ◽

Hiv Infection ◽

Northeast China ◽

Transmitted Drug Resistance ◽

Newly Diagnosed ◽

Resistance Mutations ◽

Shenyang City ◽

Subtype B ◽

Recent Hiv Infection ◽

Hiv 1

Abstract Background To assess transmitted drug resistance (TDR) to tenofovir (TDF)/emtricitabine (FTC), using as pre-exposure prophylaxis, among newly diagnosed human immunodeficiency virus-1 (HIV-1)-infected residents in Shenyang city, northeast China. Methods Demographic and epidemiological information of all newly diagnosed HIV-1 infected residents in Shenyang city from 2016 to 2018 were anonymously collected from the local HIV epidemic database. HIV-1 pol sequences were amplified from RNA in cryopreserved plasma samples and sequenced directly. Viral subtypes were inferred with phylogenetic analysis and drug resistance mutations (DRMs) were determined according to the Stanford HIVdb algorithm. Recent HIV infection was determined with HIV Limiting Antigen avidity electro immunoassay. Results A total of 2176 sequences (92.4%, 2176/2354) were obtained; 70.9% (1536/2167) were CRF01_AE, followed by CRF07_BC (18.0%, 391/2167), subtype B (4.7%, 102/2167), other subtypes (2.6%, 56/2167), and unique recombinant forms (3.8%, 82/2167). The prevalence of TDR was 4.9% (107/2167), among which, only 0.6% (13/2167) was resistance to TDF/FTC. Most of these subjects had CRF01_AE strains (76.9%, 10/13), were unmarried (76.9%, 10/13), infected through homosexual contact (92.3%, 12/13), and over 30 years old (median age: 33). The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). Recent HIV infection accounted for only 23.1% (3/13). Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%). Conclusions The prevalence of TDR to TDF/FTC is low among newly diagnosed HIV-infected cases in Shenyang, suggesting that TDR may have little impact on the protective effect of the ongoing CROPrEP project in Shenyang city.

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Genetic diversity and primary resistance among HIV-1-positive patients from Maringá, Paraná, Brazil

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652012000400005 ◽

2012 ◽

Vol 54 (4) ◽

pp. 207-213 ◽

Cited By ~ 8

Author(s):

Karine Vieira Gaspareto ◽

Flávia Myrian Martins de Almeida Mello ◽

José Ricardo Colleti Dias ◽

Vera Alice Fernandes Meneguetti ◽

Marta Evelyn Giansante Storti ◽

...

Keyword(s):

Specific Antigen ◽

Resistance Mutation ◽

Drug Resistance Mutation ◽

Subtype C ◽

Primary Resistance ◽

Subtype B ◽

Pcr Products ◽

Treatment Naïve ◽

Positive Treatment ◽

Hiv 1

The objective of this study is to identify subtypes of Human Immunodeficiency Virus type 1 (HIV-1) and to analyze the presence of mutations associated to antiretroviral resistance in the protease (PR) and reverse transcriptase (RT) regions from 48 HIV-1 positive treatment naïve patients from an outpatient clinic in Maringá, Paraná, Brazil. Sequencing was conducted using PR, partial RT and group-specific antigen gene (gag) nested PCR products from retrotranscribed RNA. Transmitted resistance was determined according to the Surveillance Drug Resistance Mutation List (SDRM) algorithm. Phylogenetic and SimPlot analysis of concatenated genetic segments classified sequences as subtype B 19/48 (39.6%), subtype C 12/48 (25%), subtype F 4/48 (8.3%), with 13/48 (27.1%) recombinant forms. Most recombinant forms were B mosaics (B/F 12.5%, B/C 10.4%), with one C/F (2.1%) and one complex B/C/F mosaic (2.1%). Low levels of transmitted resistance were found in this study, 2/48 (2.1% to NRTIs and 2.1% for PI). This preliminary data may subsidize the monitoring of the HIV evolution in the region.

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Efficiencies of Four Versions of the AMPLICOR HIV-1 MONITOR Test for Quantification of Different Subtypes of Human Immunodeficiency Virus Type 1

Journal of Clinical Microbiology ◽

10.1128/jcm.37.1.110-116.1999 ◽

1999 ◽

Vol 37 (1) ◽

pp. 110-116 ◽

Cited By ~ 74

Author(s):

K. Triques ◽

J. Coste ◽

J. L. Perret ◽

C. Segarra ◽

E. Mpoudi ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Viral Load ◽

Pcr Primers ◽

Load Test ◽

Subtype C ◽

Subtype B ◽

Immunodeficiency Virus ◽

Subtype A ◽

Hiv 1

Three versions of a commercial human immunodeficiency virus (HIV) type 1 (HIV-1) load test (the AMPLICOR HIV-1 MONITOR Test versions 1.0, 1.0+, and 1.5; Roche Diagnostics, Branchburg, N.J.) were evaluated for their ability to detect and quantify HIV-1 RNA of different genetic subtypes. Plasma samples from 96 patients infected with various subtypes of HIV-1 (55 patients infected with subtype A, 9 with subtype B, 21 with subtype C, 2 with subtype D, 7 with subtype E, and 2 with subtype G) and cultured virus from 29 HIV-1 reference strains (3 of subtype A, 6 of subtype B, 5 of subtype C, 3 of subtype D, 8 of subtype E, 3 of subtype F, and 1 of subtype G) were tested. Detection of subtypes A and E was significantly improved with versions 1.0+ and 1.5 compared to that with version 1.0, whereas detection of subtypes B, C, D, and G was equivalent with the three versions. Versions 1.0, 1.0+, and 1.5 detected 65, 98, and 100% of the subtype A-infected samples from patients, respectively, and 71, 100, and 100% of the subtype E-infected samples from patients, respectively. Version 1.5 yielded a significant increase in viral load for samples infected with subtypes A and E (greater than 1 log10 HIV RNA copies/ml). For samples infected with subtype B, C, and D and tested with version 1.5, only a slight increase in viral load was observed (<0.5 log10). We also evaluated a prototype automated version of the test that uses the same PCR primers as version 1.5. The results with the prototype automated test were highly correlated with those of the version 1.5 test for all subtypes, but were lower overall. The AMPLICOR HIV-1 MONITOR Test, version 1.5, yielded accurate measurement of the HIV load for all HIV-1 subtypes tested, which should allow the test to be used to assess disease prognosis and response to antiretroviral treatment in patients infected with a group M HIV-1 subtype.

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Effect of HIV Envelope Vaccination on the Subsequent Antibody Response to HIV Infection

mSphere ◽

10.1128/msphere.00738-19 ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Zanele Ditse ◽

Nonhlanhla N. Mkhize ◽

Michael Yin ◽

Michael Keefer ◽

David C. Montefiori ◽

...

Keyword(s):

Immune Responses ◽

Hiv Infection ◽

South African ◽

Phase 1 ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Tier 2 ◽

Subtype C ◽

Hiv Envelope ◽

Hiv 1

ABSTRACT Analysis of breakthrough HIV-1 infections could elucidate whether prior vaccination primes relevant immune responses. Here, we measured HIV-specific antibody responses in 14 South African volunteers who acquired HIV infection after participating in phase 1/2 trials of envelope-containing immunogens. Serum samples were collected annually following HIV-1 infection from participants in trials HVTN 073 (subtype C, DNA/MVA, phase 1 trial, n = 1), HVTN 086 (subtype C, DNA/MVA/gp140 protein, phase 1 trial, n = 2), and HVTN 204 (multisubtype, DNA/adenovirus serotype 5 [Ad5], phase 2 trial, n = 7) and 4 placebo recipients. Binding and neutralizing antibody responses to Env proteins and peptides were determined pre- and post-HIV infection using an enzyme-linked immunosorbent assay and the TZM-bl cell neutralization assay, respectively. HIV-infected South African individuals served as unvaccinated controls. Binding antibodies to gp41, V3, V2, the membrane-proximal external region (MPER), and the CD4 binding site were detected from the first year of HIV-1 subtype C infection, and the levels were similar in vaccinated and placebo recipients. Neutralizing antibody responses against tier 1A viruses were detected in all participants, with the highest titers being to a subtype C virus, MW965.26. No responses were observed just prior to infection, indicating that vaccine-primed HIV-specific antibodies had waned. Sporadic neutralization activity against tier 2 isolates was observed after 2 to 3 years of HIV infection, but these responses were similar in the vaccinated and placebo groups as well as the unvaccinated controls. Our data suggest that prior vaccination with these immunogens did not alter the antibody responses to HIV-1 infection, nor did it accelerate the development of HIV neutralization breadth. IMPORTANCE There is a wealth of information on HIV-specific vaccine-induced immune responses among HIV-uninfected participants; however, data on immune responses among participants who acquire HIV after vaccination are limited. Here we show that HIV-specific binding antibody responses in individuals with breakthrough HIV infections were not affected by prior vaccination with HIV envelope-containing immunogens. We also found that these vectored vaccines did not prime tier 2 virus-neutralizing antibody responses, which are thought to be required for prevention against HIV acquisition, or accelerate the development of neutralization breadth. Although this study is limited, such studies can provide insights into whether vaccine-elicited antibody responses are boosted by HIV infection to acquire broader neutralizing activity, which may help to identify antigens relevant to the design of more effective vaccines.

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