Combination anti-HIV-1 antibody therapy is associated with increased virus-specific T cell immunity.

Combination antiretroviral therapy (ART) is highly effective in controlling human immunodeficiency virus (HIV)-1 but requires lifelong medication due to the existence of a latent viral reservoir1,2. Potent broadly neutralizing antibodies (bNAbs) represent a potential alternative or adjuvant to ART. In addition to suppressing viremia, bNAbs may have T cell immunomodulatory effects as seen for other forms of immunotherapy3. However, this has not been established in individuals who are infected with HIV-1. Here, we document increased HIV-1 Gag-specific CD8+ T cell responses in the peripheral blood of all nine study participants who were infected with HIV-1 with suppressed blood viremia, while receiving bNAb therapy during ART interruption4. Increased CD4+ T cell responses were detected in eight individuals. The increased T cell responses were due both to newly detectable reactivity to HIV-1 Gag epitopes and the expansion of pre-existing measurable responses. These data demonstrate that bNAb therapy during ART interruption is associated with enhanced HIV-1-specific T cell responses. Whether these augmented T cell responses can contribute to bNAb-mediated viral control remains to be determined.

Combination of quadruplex qPCR and next-generation sequencing for qualitative and quantitative analysis of the HIV-1 latent reservoir.

HIV-1 infection requires lifelong therapy with antiretroviral drugs due to the existence of a latent reservoir of transcriptionally inactive integrated proviruses. The goal of HIV-1 cure research is to eliminate or functionally silence this reservoir. To this end, there are numerous ongoing studies to evaluate immunological approaches, including monoclonal antibody therapies. Evaluating the results of these studies requires sensitive and specific measures of the reservoir. Here, we describe a relatively high-throughput combined quantitative PCR (qPCR) and next-generation sequencing method. Four different qPCR probes covering the packaging signal (PS), group-specific antigen (gag), polymerase (pol), and envelope (env) are combined in a single multiplex reaction to detect the HIV-1 genome in limiting dilution samples followed by sequence verification of individual reactions that are positive for combinations of any two of the four probes (Q4PCR). This sensitive and specific approach allows for an unbiased characterization of the HIV-1 latent reservoir.

Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption.

The role of lymphoid tissue as a potential source of HIV-1 rebound following interruption of antiretroviral therapy (ART) is uncertain. To address this issue, we compared the latent viruses obtained from CD4+ T cells in peripheral blood and lymph nodes to viruses emerging during treatment interruption. Latent viruses were characterized by sequencing near-full-length (NFL) proviral DNA and env from viral outgrowth assays (VOAs). Five HIV-1-infected individuals on ART were studied, four of whom participated in a clinical trial of a TLR9 agonist that included an analytical treatment interruption. We found that 98% of intact or replication-competent clonal sequences overlapped between blood and lymph node. In contrast, there was no overlap between 205 latent reservoir and 125 rebound sequences in the four individuals who underwent treatment interruption. However, rebound viruses could be accounted for by recombination. The data suggest that CD4+ T cells carrying latent viruses circulate between blood and lymphoid tissues in individuals on ART and support the idea that recombination may play a role in the emergence of rebound viremia.IMPORTANCE HIV-1 persists as a latent infection in CD4+ T cells that can be found in lymphoid tissues in infected individuals during ART. However, the importance of this tissue reservoir and its contribution to viral rebound upon ART interruption are not clear. In this study, we sought to compare latent HIV-1 from blood and lymph node CD4+ T cells from five HIV-1-infected individuals. Further, we analyzed the contribution of lymph node viruses to viral rebound. We observed that the frequencies of intact proviruses were the same in blood and lymph node. Moreover, expanded clones of T cells bearing identical proviruses were found in blood and lymph node. These latent reservoir sequences did not appear to be the direct origin of rebound virus. Instead, latent proviruses were found to contribute to the rebound compartment by recombination.

Relationship between intact HIV-1 proviruses in circulating CD4+ T cells and rebound viruses emerging during treatment interruption.

Combination antiretroviral therapy controls but does not cure HIV-1 infection because a small fraction of cells harbor latent viruses that can produce rebound viremia when therapy is interrupted. The circulating latent virus reservoir has been documented by a variety of methods, most prominently by viral outgrowth assays (VOAs) in which CD4+ T cells are activated to produce virus in vitro, or more recently by amplifying proviral near full-length (NFL) sequences from DNA. Analysis of samples obtained in clinical studies in which individuals underwent analytical treatment interruption (ATI), showed little if any overlap between circulating latent viruses obtained from outgrowth cultures and rebound viruses from plasma. To determine whether intact proviruses amplified from DNA are more closely related to rebound viruses than those obtained from VOAs, we assayed 12 individuals who underwent ATI after infusion of a combination of two monoclonal anti-HIV-1 antibodies. A total of 435 intact proviruses obtained by NFL sequencing were compared with 650 latent viruses from VOAs and 246 plasma rebound viruses. Although, intact NFL and outgrowth culture sequences showed similar levels of stability and diversity with 39% overlap, the size of the reservoir estimated from NFL sequencing was larger than and did not correlate with VOAs. Finally, intact proviruses documented by NFL sequencing showed no sequence overlap with rebound viruses; however, they appear to contribute to recombinant viruses found in plasma during rebound.

Combination therapy with anti-HIV-1 antibodies maintains viral suppression.

Individuals infected with HIV-1 require lifelong antiretroviral therapy, because interruption of treatment leads to rapid rebound viraemia. Here we report on a phase 1b clinical trial in which a combination of 3BNC117 and 10-1074, two potent monoclonal anti-HIV-1 broadly neutralizing antibodies that target independent sites on the HIV-1 envelope spike, was administered during analytical treatment interruption. Participants received three infusions of 30 mg kg-1 of each antibody at 0, 3 and 6 weeks. Infusions of the two antibodies were generally well-tolerated. The nine enrolled individuals with antibody-sensitive latent viral reservoirs maintained suppression for between 15 and more than 30 weeks (median of 21 weeks), and none developed viruses that were resistant to both antibodies. We conclude that the combination of the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 can maintain long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.

Relationship between latent and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117.

A clinical trial was performed to evaluate 3BNC117, a potent anti-HIV-1 antibody, in infected individuals during suppressive antiretroviral therapy and subsequent analytical treatment interruption (ATI). The circulating reservoir was evaluated by quantitative and qualitative viral outgrowth assay (Q2VOA) at entry and after 6 mo. There were no significant quantitative changes in the size of the reservoir before ATI, and the composition of circulating reservoir clones varied in a manner that did not correlate with 3BNC117 sensitivity. 3BNC117 binding site amino acid variants found in rebound viruses preexisted in the latent reservoir. However, only 3 of 217 rebound viruses were identical to 868 latent viruses isolated by Q2VOA and near full-length sequencing. Instead, 63% of the rebound viruses appeared to be recombinants, even in individuals with 3BNC117-resistant reservoir viruses. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating latent reservoir, but frequently appear to represent recombinants of latent viruses.

Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo.

Non-neutralizing antibodies (nnAbs) to HIV-1 show little measurable activity in prevention or therapy in animal models yet were the only correlate of protection in the RV144 vaccine trial. To investigate the role of nnAbs on HIV-1 infection in vivo, we devised a replication-competent HIV-1 reporter virus that expresses a heterologous HA-tag on the surface of infected cells and virions. Anti-HA antibodies bind to, but do not neutralize, the reporter virus in vitro. However, anti-HA protects against infection in humanized mice and strongly selects for nnAb-resistant viruses in an entirely Fc-dependent manner. Similar results were also obtained with tier 2 HIV-1 viruses using a human anti-gp41 nnAb, 246D. While nnAbs are demonstrably less effective than broadly neutralizing antibodies (bNAbs) against HIV-1 in vitro and in vivo, the data show that nnAbs can protect against and alter the course of HIV-1 infection in vivo. PAPERCLIP.

HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption.

Interruption of combination antiretroviral therapy in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117,a broad and potent neutralizing antibody against the CD4 binding site of the HIV-1 Env protein, during analytical treatment interruption in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Results show that two or four 30 mg kg(-1) 3BNC117 infusions,separated by 3 or 2 weeks, respectively, are generally well tolerated.Infusions are associated with a delay in viral rebound of 5-9 weeks after two infusions, and up to 19 weeks after four infusions, or an average of 6.7 and 9.9 weeks, respectively, compared with 2.6 weeks for historical controls (P < 0.00001). Rebound viruses arise predominantly from a single provirus. In most individuals,emerging viruses show increased resistance, indicating escape.However, 30% of participants remained suppressed until antibody concentrations waned below 20 µg ml(-1), and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9-19 weeks.We conclude that the administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during analytical treatment interruption in humans.

Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo.

Antiretroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life cycle. In addition, antibodies also have the potential to guide host immune effector cells to kill HIV-1-infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by passively administered 3BNC117, a broadly neutralizing antibody, suggested that the effects of the antibody are not limited to free viral clearance and blocking new infection but also include acceleration of infected cell clearance. Consistent with these observations, we find that broadly neutralizing antibodies can target CD4(+) T cells infected with patient viruses and can decrease their in vivo half-lives by a mechanism that requires Fcγ receptor engagement in a humanized mouse model. The results indicate that passive immunotherapy can accelerate elimination of HIV-1-infected cells.

Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice.

Latent reservoirs of HIV-1-infected cells are refractory to antiretroviral therapies (ART) and remain the major barrier to curing HIV-1. Because latently infected cells are long-lived, immunologically invisible, and may undergo homeostatic proliferation, a "shock and kill" approach has been proposed to eradicate this reservoir by combining ART with inducers of viral transcription. However, all attempts to alter the HIV-1 reservoir in vivo have failed to date. Using humanized mice, we show that broadly neutralizing antibodies (bNAbs) can interfere with establishment of a silent reservoir by Fc-FcR-mediated mechanisms. In established infection, bNAbs or bNAbs plus single inducers are ineffective in preventing viral rebound. However, bNAbs plus a combination of inducers that act by independent mechanisms synergize to decrease the reservoir as measured by viral rebound. Thus, combinations of inducers and bNAbs constitute a therapeutic strategy that impacts the establishment and maintenance of the HIV-1 reservoir in humanized mice.

Revaccination with 7-valent pneumococcal conjugate vaccine elicits better serologic response than 23-valent pneumococcal polysaccharide vaccine in HIV-infected adult patients who have undergone primary vaccination with 23-valent pneumococcal polysaccharide vaccine in the era of combination antiretroviral therapy.

HIV-infected adults who had received 23-valent pneumococcal polysaccharide vaccine (PPV23) five years or more earlier consecutively underwent revaccination with one dose of PPV23 (127 subjects) from December 2005 through October 2007, or upon change in standard of care, non-randomly one (50) or two doses (44) of 7-valent pneumococcal conjugate vaccine (PCV7) from October 2008 through June 2010. Serologic response was defined as ≥ 2-fold increase in the IgG level plus a level ≥ 1000ng/ml 48 weeks following revaccination. At week 48, the response rate was significantly higher in the 2-dose PCV7 group compared with that in the 1-dose PCV7 or PPV23 group (63.6% vs 32.0% vs 8.7%, respectively; P<0.05). Revaccination with one dose of PCV7 (AOR, 4.57), two doses of PCV7 (AOR, 22.66), and CD4 >350 cells/µl (AOR, 3.24) and undetectable viral load (AOR, 3.87) at revaccination were statistically significantly associated with a better serologic response at week 48. Despite the limitation that study arms were neither randomized nor contemporaneous, we conclude that revaccination with PCV7 appears to elicit a better serologic response than PPV23 in the HIV-infected adults who have received PPV23 five years or more earlier (clinical trial registration number: NCT00885625).

Serologic response to primary vaccination with 7-valent pneumococcal conjugate vaccine is better than with 23-valent pneumococcal polysaccharide vaccine in HIV-infected patients in the era of combination antiretroviral therapy.

OBJECTIVES: The objectives of this study were to compare the serologic responses at week 48 to primary vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV) vs. 7-valent pneumococcal conjugate vaccine (PCV); and to identify factors associated with serologic response in HIV-infected adult patients with access to combination antiretroviral therapy (cART). METHODS: One hundred and four CD4-matched pairs of HIV-infected patients who underwent primary pneumococcal vaccination with 23-valent PPV or 7-valent PCV were enrolled for determinations of anti-capsular antibody responses against four serotypes (6B, 14, 19F and 23F) at baseline, 24 weeks and 48 weeks following vaccination. Significant antibody responses were defined as 2-fold or greater increase of antibody levels at week 48 compared with baseline. The logistic regression model was used to determine the factors associated with serologic response to at least one and two serotypes. RESULTS: At week 48, patients who received PCV demonstrated a statistically significantly higher response rate to at least 2 serotypes than those who received PPV (37.5% vs. 20.2%, p = 0.006). In multivariate analysis, factors associated with significant antibody responses to at least one or two serotypes included receipt of PCV (adjusted odds ratio [AOR], 2.42 [95% CI, 1.23-4.78] and 3.58 [95% CI. 1.76-7.28], respectively), and undetectable plasma HIV RNA load (< 400 copies/ml) at vaccination (AOR, 1.47 [95% CI, 0.60-3.64] and 3.62 [95% CI, 1.11-11.81], respectively). CONCLUSIONS: Primary vaccination with 7-valent PCV achieved a significantly better serologic responses to one or two out of the four serotypes studied at week 48 than with 23-valent PPV in HIV-infected patients in the cART era. Suppression of HIV replication when primary vaccination was administered was associated with better serologic responses.

Mycobacterium avium complex infection-related immune reconstitution inflammatory syndrome of the central nervous system in an HIV-infected patient: case report and review.

Disseminated Mycobacterium avium complex (MAC) infection involves the central nervous system (CNS) less frequently than tuberculosis, and MAC-related immune reconstitution inflammatory syndrome (IRIS) of the CNS in AIDS patients is even more rarely described. We report a case of MAC-related IRIS of the CNS in an HIV-infected patient who presented with meningoencephalitis and myelitis 2 months after discontinuation of antiMAC therapy, when he had achieved prolonged suppression of HIV replication and restoration of CD4 counts to >100 cells/µL for 1 year. Cases of MAC-related IRIS of the CNS reported in the literature are reviewed.

Immune reconstitution inflammatory syndrome of Kaposi's sarcoma in an HIV-infected patient.

We present a case of Kaposi's sarcoma-related immune reconstitution inflammatory syndrome in an HIV-infected patient who developed fever, worsening pulmonary infiltrates with respiratory distress, and progression of skin tumors at the popliteal region and thigh that resulted in limitation on movement of the right knee joint at 3.5 months following a significant increase of CD4 count after combination antiretroviral therapy.

Comparative effectiveness of two doses versus three doses of hepatitis A vaccine in human immunodeficiency virus-infected and -uninfected men who have sex with men.

UNLABELLED: The purpose of this prospective cohort study was to compare the serologic response between human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) receiving two and three doses of hepatitis A virus (HAV) vaccine and HIV-uninfected MSM receiving two doses of HAV vaccine. Between June 2009 and December 2010, 582 MSM aged 18 to 40 years who were seronegative for HAV were enrolled in the study. HIV-infected MSM received either two doses of HAV vaccine (1,440 enzyme-linked immunosorbent assay units) (n = 140) with the second dose given at week 24 or three doses (n = 225) with the second and third dose given at weeks 4 and 24, respectively, while HIV-uninfected MSM (n = 217) received two doses. The primary endpoint was seroconversion at week 48. The geometric mean concentration (GMC) of anti-HAV antibody was determined at weeks 48 and 72. At week 48, the seroconversion rate was 75.7%, 77.8%, and 88.5% in intention-to-treat analysis for two-dose HIV-infected, three-dose HIV-infected, and two-dose HIV-uninfected MSM, respectively. The GMC of anti-HAV antibody at week 48 for three-dose HIV-infected MSM (2.29 ± 0.73 log10 mIU/mL) was significantly higher than that for two-dose HIV-infected MSM (1.94 ± 0.66; P < 0.01), but was lower than HIV-uninfected MSM (2.49 ± 0.42; P < 0.01). Multivariate analysis revealed higher CD4 counts (adjusted odds ratio [AOR] for per 50 cells/µL increase, 1.13; 95% confidence interval [CI], 1.05-1.21) and undetectable plasma HIV RNA load (AOR, 1.90; 95% CI, 1.10-3.28) before HAV vaccination were predictive of seroconversion in HIV-infected patients. CONCLUSION: Serologic response rate to three and two doses of HAV vaccine was similar in HIV-infected MSM, which was lower than that in HIV-uninfected MSM receiving two doses. HAV vaccination in HIV-infected patients with a higher CD4 count and suppression of HIV replication increased the seroconversion rate.

Seroprevalence of hepatitis virus infection in men who have sex with men aged 18-40 years in Taiwan.

BACKGROUND/PURPOSE: Men who have sex with men (MSM) are at increased risk for hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections than the general population. Comparisons of the seroprevalence rates of these hepatitis viruses between HIV-positive and HIV-negative MSM are rarely performed in Taiwan. METHODS: Between January 2009 and June 2010, data on the serologies for HAV, HBV, and HCV were collected from two groups of patients: HIV-negative MSM, aged 18-40 years, who sought voluntary counseling and testing (VCT) for HIV infection, and HIV-positive MSM of the same age group who sought HIV care at the National Taiwan University Hospital. Both groups of patients were also tested for syphilis. RESULTS: During the 18-month study period, 690 HIV-negative MSM and 438 HIV-positive MSM were enrolled and tested for anti-HAV antibody, HBV surface antigen (HBsAg), hepatitis B core antibody (anti-HBc antibody), and anti-HCV antibody. HIV-positive MSM were older than HIV-negative MSM (30.5 ± 5.4 vs. 25.8 ± 4.7 years, p < 0.01). For HIV-positive MSM, the mean CD4 lymphocyte count was 477.6 ± 230.0 cells/µL and 46% of them had undetectable plasma HIV RNA load (< 40 copies/mL by reverse transcription-polymerase chain reaction assay). The overall seroprevalence rates of HAV, HBsAg, and HCV in HIV-positive MSM were 15.1%, 16.4%, and 5.5%, respectively, while in HIV-negative MSM, they were 7.4%, 6.2%, and 0.4%, respectively. In the multivariate analysis, age was significantly associated with seropositivity for HAV (OR [per one age group increase]: 1.96; 95% CI: 1.6-2.5), HBsAg (OR: 2.02; 95% CI: 1.6-2.6), anti-HBc (OR: 2.68; 95% CI: 2.3-3.2), anti-HCV (OR: 1.67; 95% CI: 1.0-2.7), and anti-HBs (OR: 1.25; 95% CI: 1.0-1.5). HIV infection was associated with seropositivity for HBsAg (OR: 1.73; 95% CI: 1.1-2.7), anti-HBc (OR: 2.44; 95% CI: 1.8-3.3), HCV (OR: 8.91; 95% CI: 2.5-31.4), and syphilis (OR: 11.21; 95% CI: 6.7-18.9). CONCLUSION: HIV-positive MSM have a higher seroprevalence rate of HBV and HCV infection than HIV-negative MSM in Taiwan. Vaccination and safe-sex counseling should be provided to prevent the transmission of hepatitis viruses among MSM who may be engaged in high-risk behaviors.

Impact of vaccination with seven-valent pneumococcal conjugate vaccine on virologic and immunologic outcomes among HIV-infected adult patients in the era of highly active antiretroviral therapy.

BACKGROUND/PURPOSE: Pneumococcal polysaccharide vaccination may be associated with adverse outcomes in HIV-infected individuals who did not receive highly active antiretroviral therapy (HAART). Our aim was to evaluate the impact of vaccination with seven-valent pneumococcal conjugate vaccine (PCV) on the short-term clinical, virologic, and immunologic outcomes among HIV-infected adult patients in the HAART era. METHODS: A total of 429 HIV-infected adult patients were enrolled from October 2008 to March 2010: 213 received two doses of seven-valent PCV given at a 4-week interval and 216 received one dose. All patients were given 1-week diary to record any discomfort after vaccination. Data of serial CD4 and plasma HIV RNA load measurements were recorded. RESULTS: Of the 429 patients with a mean CD4 count of 305 cells/µL, 289 (67.4%) were receiving HAART and 175 (40.8%) had plasma HIV RNA load <40 copies/mL at vaccination. Of the 396 patients (92.3%) who returned the diary, injection site soreness (24.0%) and pain (10.4%) were the most commonly reported adverse effects. After 3-4 months of vaccination, CD4 count increased by 40 cells/µL in 278 patients (68.2%) who continued HAART, compared with a decrease of 38 cells/µL in 131 patients (31.8%) who were not on HAART (p < 0.001), while the respective change in plasma HIV RNA load was 0.8 versus 0.2 log(10) copies/mL (p = 0.09). One patient died, two developed opportunistic infections, and one developed pneumococcal pneumonia following vaccination. CONCLUSION: Vaccination with seven-valent PCV among HIV-infected patients is generally safe, which has no detrimental effect on CD4 count and plasma HIV RNA load in patients receiving HAART. (ClinicalTrials.gov number, NCT00885628).

Microbiological and clinical characteristics of vancomycin-resistant Enterococcus faecium bacteraemia in Taiwan: implication of sequence type for prognosis.

OBJECTIVES: Vancomycin-resistant enterococci (VRE), particularly vancomycin-resistant Enterococcus faecium (VREfm), have emerged among the leading pathogens causing hospital-acquired infections worldwide. We aimed to examine whether there were newly introduced clones contributing to this increase and to assess the risk factors for mortality in patients with VREfm bacteraemia. METHODS: Between 2003 and 2010, all medical records of adult patients diagnosed with VREfm bacteraemia at a university hospital in Taiwan were reviewed. Antibiotic susceptibility, genotyping and multilocus sequence typing of the VREfm isolates were performed. RESULTS: During the study period, the prevalence of non-duplicated blood VRE isolates increased significantly from 3.9% in 2003 to 18.9% in 2010 (P < 0.0001). One-hundred-and-forty-nine patients with VREfm bacteraemia were noted and 102 isolates of VREfm were available for microbiological characterization. All isolates were susceptible to daptomycin and linezolid. Sequence type (ST) 18 and ST414 were the two predominant emerging STs from 2009 to 2010, accounting for 29.7% and 25.0% of all isolates, respectively. Patients who received immunosuppressives, had a high Charlson comorbidity index or experienced septic shock had a significantly higher 14 day mortality rate. Patients who had bacteraemia caused by ST414 isolates and received appropriate antibiotics had a lower 14 day mortality rate. CONCLUSIONS: The prevalence of the VRE that caused bacteraemia increased from 2003 to 2010. This increase might be attributed to the clonal spread of VREfm belonging to ST18 and ST414. The all-cause 14 day mortality rate was lower in patients with bacteraemia due to VREfm isolates that belonged to ST414.

Comparison of serologic responses to vaccination with one dose or two doses of 7-valent pneumococcal conjugate vaccine in HIV-infected adult patients.

BACKGROUND: Vaccination with 7-valent pneumococcal conjugate vaccine (PCV) has been shown to decrease the incidence of recurrent invasive pneumococcal disease among HIV-infected adults in Africa. Longitudinal follow-up studies of serologic responses to different doses of 7-valent PCV are rarely performed in HIV-infected adult patients receiving combination antiretroviral therapy (cART). METHODS: From October 2008 to June 2010, 115 CD4-matched pairs of HIV-infected patients aged ≥ 20 years who had no prior pneumococcal vaccination received one or two doses of 7-valent PCV. Anticapsular antibodies against 4 serotypes (6B, 14, 19F, and 23F) were examined at the 12th, 24th, 36th, and 48th week following vaccination. Significant antibody responses were defined as ≥ 2-fold increase in the IgG level plus a post-vaccination antibody level ≥ 1000 ng/ml. RESULTS: The most common reported adverse effects were injection site soreness (19.3%) and pain (4.8%). Significant antibody response rate was highest for serotype 14, followed by 23F, 19F, and 6B in all of the four time points examined. At week 48, patients who received two doses of 7-valent PCV had a significantly higher response rate to serotype 6B (P=0.03) and 23F (P=0.01) than those who received one dose; moreover, the former group also had a higher response rate to at least one (P=0.03) and two serotypes (P=0.02) in intention-to-treat analysis than the latter group. CONCLUSIONS: HIV-infected adult patients on cART who received two doses of 7-valent PCV achieved better serological responses to at least one serotype than those who received one dose during the 48 weeks of follow-up.