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1.
J Acquir Immune Defic Syndr ; 90(1): 56-61, 2022 05 01.
Article in English | MEDLINE | ID: mdl-35044991

ABSTRACT

BACKGROUND: Persons with acute HIV infection (AHI) are highly infectious and responsible for a disproportionate share of incident infections. Immediate antiretroviral therapy (ART) rapidly reduces blood viral loads (VLs), but genital VLs after ART initiation during AHI are less well described. SETTING: Lilongwe, Malawi, 2012-2014. METHODS: HIV-seronegative and HIV-serodiscordant persons aged ≥18 years were screened for AHI (RNA positive) and randomized to standard of care, behavioral intervention, or behavioral intervention plus short-term ART (raltegravir/emtricitabine/tenofovir) (1:2:2). Persons who were ART eligible under Malawi guidelines could receive first-line therapy. Blood and genital VLs were assessed at weeks 1, 4, 8, and 12. Fisher's Exact test was used to compare viral suppression by ART status. RESULTS: Overall, 46 persons with AHI were enrolled; of whom, 17 started ART within 12 weeks. Median blood VL at AHI diagnosis was 836,115 copies/mL. At week 12, 7% (1/14) of those who initiated ART had a blood VL of ≥400 copies/mL, compared with 100% (23/23; P < 0.0001) of those who did not initiate ART (median VL: 61,605 copies/mL). Median genital VL at week 1 was 772 copies/mL, with 13 of 22 (59%) having VL of ≥400 copies/mL. At week 12, 0 of 10 (0%) of those who initiated ART had genital VL of ≥400 copies/mL, compared with 7 of 15 (47%) of those who did not initiate ART (P = 0.02). CONCLUSION: Although highly correlated, VLs in blood and genital fluids occupy discrete biological compartments with distinct virologic dynamics. Our results corroborate the dramatic reduction in both compartments after ART initiation. Increasing AHI screening and rapidly initiating treatment is key to interrupting transmission.


Subject(s)
Anti-HIV Agents , HIV Infections , Adolescent , Adult , Anti-HIV Agents/therapeutic use , Genitalia , HIV Infections/diagnosis , Humans , Malawi , Viral Load
2.
JMIR Public Health Surveill ; 7(10): e26177, 2021 10 27.
Article in English | MEDLINE | ID: mdl-34228627

ABSTRACT

BACKGROUND: Men who have sex with men (MSM) are a key group for HIV interventions in Malawi considering their high HIV prevalence (17.5% compared to 8.4% among men in the general population). The use of oral preexposure prophylaxis (PrEP) presents a new opportunity for MSM to be protected. We present the findings from a qualitative assessment designed to assess awareness of and willingness and barriers to using PrEP among MSM in Malawi. OBJECTIVE: The 3 main objectives of this assessment were to determine: (1) awareness of PrEP, (2) factors that influence willingness to use PrEP, and (3) potential barriers to PrEP use and adherence among MSM in order to guide the design and implementation of a PrEP program in Malawi. METHODS: Ahead of the introduction of PrEP in Malawi, a qualitative study using in-depth interviews (IDIs) and focus group discussions (FGDs) was conducted in October 2018 in Blantyre, Lilongwe, and rural districts of Mzimba North and Mangochi. With support of members of the population, study participants were purposively recruited from 4 MSM-friendly drop-in centers where MSM receive a range of health services to ensure representativeness across sites and age. Participants were asked what they had heard about PrEP, their willingness to use PrEP, their barriers to PrEP use, and their preferences for service delivery. The data were analyzed using a thematic content analysis framework that was predetermined in line with objectives. RESULTS: A total of 109 MSM were interviewed-13 through IDIs and 96 through FGDs. Most participants were aware of PrEP as a new HIV intervention but had limited knowledge related to its use. However, the majority were willing to use it and were looking forward to having access to it. IDI participants indicated that they will be more willing to take PrEP if the dosing frequency were appropriate and MSM were involved in information giving and distribution of the drug. FGD participants emphasized that places of distribution and characteristics of the service provider are the key factors that will affect use. Knowing the benefits of PrEP emerged as a key theme in both the IDIs and FGDs. Participants highlighted barriers that would hinder them from taking PrEP such as side effects which were cited in IDIs and FGDs. Key factors from FGDs include cost, fear of being outed, drug stockouts, fear of being known as MSMs by wives, and lack of relevant information. FGDs cited stigma from health care workers, forgetfulness, and community associated factors. CONCLUSIONS: Despite having inadequate knowledge about PrEP, study participants were largely willing to use PrEP if available. Programs should include an effective information, education, and communication component around their preferences and provide PrEP in MSM-friendly sites.


Subject(s)
HIV Infections , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Focus Groups , HIV Infections/epidemiology , HIV Infections/prevention & control , Homosexuality, Male , Humans , Malawi/epidemiology , Male
3.
Sex Transm Dis ; 48(6): e68-e72, 2021 06 01.
Article in English | MEDLINE | ID: mdl-32925596

ABSTRACT

ABSTRACT: Monitoring the burden of and trends in sexually transmitted infection syndromes is useful in informing syndromic management guidelines. Among sexually transmitted infection clinic patients in Lilongwe, Malawi, between 2006 and 2015, genital discharge, lower abdominal pain, and genital ulcer syndromes were common. Prevalence of most syndromes remained stable during the 10-year period.


Subject(s)
Sexually Transmitted Diseases , Humans , Malawi/epidemiology , Prevalence , Sexually Transmitted Diseases/epidemiology , Syndrome , Ulcer
4.
AIDS Educ Prev ; 32(3): 260-270, 2020 06.
Article in English | MEDLINE | ID: mdl-32749877

ABSTRACT

We implemented HPTN 062, an acceptability and feasibility study of a motivational-interviewing (MI) intervention to reduce HIV transmission among individuals with acute HIV infection (AHI) in Lilongwe, Malawi. Participants were randomly assigned to receive either brief education or the MI intervention over 24 weeks; all participants received the same messages about AHI. We used mixed methods to assess participants' understanding of the association between AHI and viral load, and its connection to sexual behavior at 8 weeks. While most participants understood key aspects of AHI, MI-intervention participants gave substantially more detailed descriptions of their understanding. Nearly all participants, regardless of study arm, understood that they were highly infectious and would be very likely to transmit HIV after unprotected sex during AHI. Our findings suggest that messages about AHI delivered during the period of AHI are likely beneficial for ensuring that those with AHI understand their level of infectiousness and its association with forward transmission.


Subject(s)
Anti-HIV Agents/therapeutic use , Disease Transmission, Infectious/prevention & control , HIV Infections/drug therapy , HIV Infections/psychology , Motivational Interviewing , Patient Education as Topic/methods , Sexual Behavior , Acute Disease , Adult , Feasibility Studies , Female , HIV Infections/prevention & control , HIV Infections/transmission , Health Knowledge, Attitudes, Practice , Humans , Malawi , Male , Middle Aged , Outcome Assessment, Health Care , Sexual Behavior/psychology , Sexual Behavior/statistics & numerical data , Unsafe Sex , Viral Load , Young Adult
5.
Open Forum Infect Dis ; 6(1): ofy341, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30648131

ABSTRACT

BACKGROUND: Persons with acute HIV infection (AHI) have heightened transmission risk. We evaluated potential transmission reduction using behavioral and biomedical interventions in a randomized controlled pilot study in Malawi. METHODS: Persons were randomized 1:2:2 to standard counseling (SC), 5-session behavioral intervention (BI), or behavioral intervention plus 12 weeks of antiretrovirals (ARVs; BIA). All were followed for 26-52 weeks and, regardless of arm, referred for treatment according to Malawi-ARV guidelines. Participants were asked to refer partners for testing. RESULTS: Among 46 persons (9 SC, 18 BI, 19 BIA), the average age was 28; 61% were male. The median viral load (VL) was 5.9 log copies/mL at enrollment. 67% (10/15) of BIA participants were suppressed (<1000 copies/mL) at week 12 vs 25% BI and 50% SC (P = .07). Although the mean number of reported condomless sexual acts in the past week decreased from baseline across all arms (1.5 vs 0.3 acts), 36% experienced incident sexually transmitted infection by 52 weeks (12% SC, 28% BI, 18% BIA). Forty-one percent (19/46) of participants referred partners (44% SC, 44% BI, 37% BIA); 15 of the partners were HIV-infected. CONCLUSIONS: Diagnosis of AHI facilitates behavioral and biomedical risk reduction strategies during a high-transmission period that begins years before people are typically identified and started on ARVs. Sexually transmitted infection incidence in this cohort suggests ongoing risk behaviors, reinforcing the importance of early intervention with ARVs to reduce transmission. Early diagnosis coupled with standard AHI counseling and early ARV referral quickly suppresses viremia, may effectively change behavior, and could have tremendous public health benefit in reducing onward transmission.

6.
Clin Infect Dis ; 69(5): 853-860, 2019 08 16.
Article in English | MEDLINE | ID: mdl-30476007

ABSTRACT

BACKGROUND: Understanding sexual networks involving acute human immunodeficiency virus (HIV)-1 infections (AHI) may lead to prevention opportunities to mitigate high rates of onward transmission. We evaluated HIV-1 phylogenetic and behavioral characteristics among persons with AHI and their referred partners. METHODS: Between 2012 and 2014, 46 persons with AHI in Malawi participated in a combined behavioral and biomedical intervention. Participants referred sexual partners by passive referral. Demographics and sexual behaviors were collected through interviews and HIV-1 genetic relationships were assessed with phylogenetics. RESULTS: Among 45 AHI participants with HIV-1 sequences, none was phylogenetically-linked with another AHI index. There were 19 (42%) AHI participants who referred a single partner that returned for testing. Most partners (n = 17) were HIV-infected, with 15 (88%) presenting with an established infection. There were 14 index-partner pairs that had sequences available; 13 (93%) pairs were phylogenetically-linked dyads. The AHI index was female in 7/13 (54%) dyads. Age-disparate relationships among dyads were common (≥5-year age difference in 67% of dyads), including 3/6 dyads involving a male index and a younger woman. Index participants with a referred partner were more likely to report no casual partners and to be living with their current partner than participants not in dyads. CONCLUSIONS: Passive-partner referral successfully identified partners with genetically-similar HIV infections-the likely source of infection-but only 40% of index cases referred partners who presented for HIV-1 testing. Future work evaluating assisted partner notification may help reach susceptible partners or more people with untreated HIV-1 infections connected to acute transmission. CLINICAL TRIALS REGISTRATION: NCT01450189.


Subject(s)
Demography/statistics & numerical data , HIV Infections/transmission , HIV-1/genetics , Phylogeny , Sexual Behavior/statistics & numerical data , Acute Disease/epidemiology , Adult , Contact Tracing , Female , HIV Infections/epidemiology , HIV-1/classification , Humans , Malawi/epidemiology , Male , Sexual Partners , Young Adult
7.
PLoS One ; 13(7): e0201265, 2018.
Article in English | MEDLINE | ID: mdl-30048496

ABSTRACT

Diagnosis of acute HIV infection (AHI) presents an opportunity to prevent HIV transmission during a highly infectious period. Disclosure is important during AHI as a means to facilitate safer sex practices and notify partners, particularly as those with AHI may be better able to identify the source of their infection because of the recency of HIV acquisition. However, little is known about disclosure during AHI. We conducted 40 semi-structured interviews with Malawians diagnosed with AHI (24 men; 21 married). Most participants reported disclosing to a sexual partner within a month of diagnosis, and knew or had a strong suspicion about the source of their infection. Participants often assumed their source had knowingly infected them, contributing to anger and feeling that disclosure is futile if the source already knew their HIV status. Assisted partner notification, individual and couples counseling, and couples HIV testing may facilitate disclosure during AHI. CLINICAL TRIAL REGISTRATION NUMBER: NCT01450189.


Subject(s)
Contact Tracing , HIV Infections/epidemiology , Sexual Partners , Acute Disease , Adolescent , Adult , Female , HIV Infections/diagnosis , HIV Infections/transmission , Humans , Malawi/epidemiology , Male , Middle Aged , Safe Sex , Sexual Behavior , Truth Disclosure , Young Adult
8.
Sex Transm Dis ; 45(11): 741-746, 2018 11.
Article in English | MEDLINE | ID: mdl-29870501

ABSTRACT

BACKGROUND: Identification of acute HIV infection (AHI) allows for important opportunities for HIV prevention through behavior change and biomedical intervention. Here, we evaluate changes in sexual risk behaviors among persons with AHI enrolled in a combined behavioral and biomedical intervention designed to reduce onward transmission of HIV. METHODS: Participants were randomized to standard HIV counseling, a multisession behavioral intervention, or a multisession behavioral intervention plus antiretrovirals. Sexual behaviors were assessed periodically over 1 year. RESULTS: Four weeks after diagnosis, the predicted probability of reporting multiple sexual partners decreased from 24% to 9%, and the probability of reporting unprotected sex decreased from 71% to 27%. These declines in sexual risk behaviors were sustained over follow-up irrespective of study arm. CONCLUSIONS: Diagnosis of AHI alone may be sufficient to achieve immediate and sustained behavior change during this highly infectious period.


Subject(s)
Counseling , HIV Infections/diagnosis , HIV Infections/prevention & control , Risk-Taking , Sexual Behavior/psychology , Sexual Behavior/statistics & numerical data , Acute Disease , Adult , Behavior Therapy , Female , Humans , Malawi/epidemiology , Male , Mass Screening , Risk Reduction Behavior , Safe Sex/statistics & numerical data , Sexual Partners/psychology , Unsafe Sex/psychology , Unsafe Sex/statistics & numerical data , Young Adult
9.
Patient Educ Couns ; 101(6): 1103-1109, 2018 06.
Article in English | MEDLINE | ID: mdl-29519656

ABSTRACT

OBJECTIVE: Individuals diagnosed with acute HIV infection (AHI) are highly infectious and require immediate HIV prevention efforts to minimize their likelihood of transmitting HIV to others. We sought to explore the relevance of Motivational Interviewing (MI), an evidence-based counseling method, for Malawians with AHI. METHODS: We designed a MI-based intervention called "Uphungu Wanga" to support risk reduction efforts immediately after AHI diagnosis. It was adapted from Options and SafeTalk interventions, and refined through formative research and input from Malawian team members and training participants. We conducted qualitative interviews with counselors and participants to explore the relevance of MI in this context. RESULTS: Intervention adaptation required careful consideration of Malawian cultural context and the needs of people with AHI. Uphungu Wanga's content was relevant and key MI techniques of topic selection and goal setting were viewed positively by counselors and participants. However, rating levels of importance and confidence did not appear to help participants to explore behavior change as intended. CONCLUSION: Uphungu Wanga may have provided some added benefits beyond "brief education" standard of care counseling for Malawians with AHI. PRACTICE IMPLICATIONS: MI techniques of topic selection and goal setting may enhance prevention education and counseling for Malawians with AHI.


Subject(s)
Counseling/methods , HIV Infections/diagnosis , HIV Infections/prevention & control , Motivational Interviewing/methods , Program Development , Program Evaluation/methods , Acute Disease , Adult , Female , HIV Infections/psychology , Humans , Malawi , Male , Middle Aged , Process Assessment, Health Care , Risk Reduction Behavior , Sexual Behavior/psychology
10.
Malawi Med J ; 30(2): 54-60, 2018 06.
Article in English | MEDLINE | ID: mdl-30627329

ABSTRACT

Introduction: Malawi published its first ever HIV and AIDS policy in 2003. The implementation of the policy provided a very necessary and historic step in Malawi's organized response towards HIV and AIDS. Many achievements were registered in the period this policy was implemented. However, some components of the policy were not well-implemented. Our study explored barriers to implementation of provider initiated HIV testing and counseling (PITC) for sexually transmitted infections (STI) within general outpatient settings. Malawi also launched a revised HIV and AIDS Policy in December 2013. Although not part of this policy analysis, future years of implementation may face related issues observed during the implementation of the 2003-2013 policy. Methods: This is a non-experimental, descriptive study using a case study design. We examined the implementation of provider initiated HIV testing and counseling component of the Malawi HIV and AIDS policy from 2003-2013 focusing on STI and outpatient clinic settings. We sought to understand perspectives of various stakeholders and users of the policy. We conducted in-depth interviews with policy makers, health care worker supervisors, health care workers and health rights activists. Results: Major problems which affected the implementation of the 2003-2013 HIV policy were: selective prioritization of policies by government, lack of involvement of implementers in the policy making process, non-awareness of health workers about the existence of the policy, lack of healthcare worker training, unsatisfactory supervision of policy implementation, poor harmonization of policies, lack of clarity about guidance to those directly implementing, unclear roles and reporting authority among the main national coordinating units. Conclusion: Good leadership, effective coordination, involvement of key players in the policy making process, dissemination to primary users and decentralization or empowerment of local supervisors is key to successful policy implementation.


Subject(s)
Delivery of Health Care/methods , HIV Infections/diagnosis , Health Policy , Mass Screening/methods , Policy Making , Sexually Transmitted Diseases/prevention & control , Ambulatory Care Facilities , Female , HIV Infections/prevention & control , Health Personnel , Humans , Malawi , Male
11.
Sci Immunol ; 2(7)2017 Jan 27.
Article in English | MEDLINE | ID: mdl-28783671

ABSTRACT

Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. Antibody 10E8, reactive with the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41, is broadly neutralizing. However, the ontogeny of distal MPER antibodies and the relationship of memory B cell to plasma bnAbs are poorly understood. HIV-1-specific memory B cell flow sorting and proteomic identification of anti-MPER plasma antibodies from an HIV-1-infected individual were used to isolate broadly neutralizing distal MPER bnAbs of the same B cell clonal lineage. Structural analysis demonstrated that antibodies from memory B cells and plasma recognized the envelope gp41 bnAb epitope in a distinct orientation compared with other distal MPER bnAbs. The unmutated common ancestor of this distal MPER bnAb was autoreactive, suggesting lineage immune tolerance control. Construction of chimeric antibodies of memory B cell and plasma antibodies yielded a bnAb that potently neutralized most HIV-1 strains.

12.
Sci Transl Med ; 9(381)2017 03 15.
Article in English | MEDLINE | ID: mdl-28298420

ABSTRACT

A preventive HIV-1 vaccine should induce HIV-1-specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3-glycan bnAb. Two autologous neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3-glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs.


Subject(s)
Antibodies, Neutralizing/metabolism , HIV-1/immunology , Polysaccharides/metabolism , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/genetics , Crystallography, X-Ray , Humans , Male , Mutation/genetics , Neutralization Tests , Phylogeny , Protein Binding , env Gene Products, Human Immunodeficiency Virus/metabolism
13.
Sex Transm Infect ; 92(8): 587-592, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27177775

ABSTRACT

OBJECTIVES: To explore acceptability of recruiting social contacts for HIV and sexually transmitted infection (STI) screening in Lilongwe, Malawi. METHODS: In this observational study, three groups of 'seed' patients were enrolled: 45 HIV-infected patients with STI, 45 HIV-uninfected patients with STI and 45 community controls, who were also tested for HIV as part of the study. Each seed was given five coupons and asked to recruit up to five social contacts to the STI clinic. Seeds were told the programme for contacts would include HIV testing, STI screening and general health promotion. Seeds were asked to return after 1 month to report on the contact recruitment process. Seeds received $2 for each successfully recruited contact. RESULTS: Eighty-nine seeds (66%) returned for 1-month follow-up with no difference between the three seed groups (p=0.9). Returning seeds reported distributing most of their coupons (mean=4.1) and discussing each feature of the programme with most contacts-HIV testing (90%), STI screening (87%) and health promotion (91%). Seeds reported discussing their own HIV status with most contacts (52%), with a lower proportion of HIV-infected seeds discussing their HIV status (22%) than HIV-uninfected seeds (81%) or community seeds (64%) (p<0.001). Contact recruitment did not vary with socioeconomic status. CONCLUSIONS: Most seeds distributed all coupons and reported describing all aspects of the programme to most contacts. Patients with STI are able to act as health promoters within their social networks and may be a critical link to increasing STI and HIV status awareness among high-risk groups.


Subject(s)
HIV Infections/diagnosis , Health Education/methods , Mass Screening/methods , Patient Acceptance of Health Care , Patient Selection , Peer Group , Social Behavior , Adolescent , Adult , Contact Tracing/economics , Contact Tracing/methods , Female , HIV Infections/complications , HIV Infections/transmission , Humans , Malawi , Male , Mass Screening/economics , Middle Aged , Motivation , Program Evaluation , Social Class , Young Adult
14.
J Acquir Immune Defic Syndr ; 71(3): 272-80, 2016 Mar 01.
Article in English | MEDLINE | ID: mdl-26428231

ABSTRACT

BACKGROUND AND OBJECTIVES: Integrating acute HIV-infection (AHI) testing into clinical settings is critical to prevent transmission, and realize potential treatment-as-prevention benefits. We evaluated acceptability of AHI testing and compared AHI prevalence at sexually transmitted infection (STI) clinics and HIV testing and counseling (HTC) clinics in Lilongwe, Malawi. METHODS: We conducted HIV RNA testing for HIV-seronegative patients visiting STI and HTC clinics. AHI was defined as positive RNA and negative/discordant rapid antibody tests. We evaluated demographic, behavioral, and transmission-risk differences between STI and HTC patients and assessed performance of a risk-score for targeted screening. RESULTS: Nearly two-thirds (62.8%, 9280/14,755) of eligible patients consented to AHI testing. We identified 59 persons with AHI (prevalence = 0.64%)-a 0.9% case-identification increase. Prevalence was higher at STI [1.03% (44/4255)] than at HTC clinics [0.3% (15/5025), P < 0.01], accounting for 2.3% of new diagnoses vs 0.3% at HTC clinic. Median viral load (VL) was 758,050 copies per milliliter; 25% (15/59) had VL ≥ 10,000,000 copies per milliliter. Median VL was higher at STI (1,000,000 copies/mL) compared with HTC (153,125 copies/mL, P = 0.2). Among persons with AHI, those tested at STI clinics were more likely to report genital sores compared with those tested at HTC clinics (54.6% vs 6.7%, P < 0.01). The risk score algorithm performed well in identifying persons with AHI at HTC clinics (sensitivity = 73%, specificity = 89%). CONCLUSIONS: The majority of patients consented to AHI testing. AHI prevalence was substantially higher in STI clinics than HTC clinics. Remarkably high VLs and concomitant genital scores demonstrate the potential for transmission. Universal AHI screening at STI clinics, and targeted screening at HTC centers, should be considered.


Subject(s)
Ambulatory Care Facilities/standards , HIV Infections/diagnosis , HIV Infections/epidemiology , Adolescent , Adult , Cross-Sectional Studies , Female , HIV Infections/virology , HIV Seronegativity , Humans , Malawi/epidemiology , Male , Middle Aged , Prevalence , RNA, Viral/blood , Risk Factors , Viral Load , Young Adult
15.
Cell Host Microbe ; 18(3): 354-62, 2015 Sep 09.
Article in English | MEDLINE | ID: mdl-26355218

ABSTRACT

The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3 and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.


Subject(s)
Antibodies, Neutralizing/immunology , CD4-Positive T-Lymphocytes/virology , HIV Antibodies/immunology , HIV Envelope Protein gp120/immunology , HIV-1/immunology , Selection, Genetic , Virus Attachment , Binding Sites , HIV Envelope Protein gp120/genetics , HIV-1/genetics , Molecular Sequence Data , Mutation , RNA, Viral/genetics , Sequence Analysis, DNA
16.
PLoS One ; 10(5): e0124452, 2015.
Article in English | MEDLINE | ID: mdl-25962118

ABSTRACT

OBJECTIVE: We pilot tested a Motivational Interviewing (MI) -based counseling intervention for individuals with Acute HIV Infection (AHI) to reduce risky sexual behavior in Lilongwe, Malawi. METHODS: Twenty-eight individuals diagnosed with AHI were randomized to receive either brief education alone, or the brief education plus the MI-based intervention, called Uphungu Wanga. Participants in Uphungu Wanga received four sessions delivered on the day of diagnosis, three days later and at weeks 1 and 2 with a booster session at week 8; participants were followed for 24 weeks from diagnosis. An interviewer administered quantitative questionnaire was conducted at baseline and at weeks 2, 4, 8, 12, 16, 20 and 24. Semi-structured qualitative interviews (SSI) were conducted at weeks 2, 8, 12, and 24. RESULTS: The majority of participants in both arms reported rapid and sustained behavior change following diagnosis with AHI. Very few participants reported having sex without a condom after diagnosis. Participants reported a trend towards fewer sex partners and abstaining from sex during study follow-up. Participants in the MI-based arm provided concrete examples of risk reduction strategies in the SSIs while those in the brief education arm primarily described reducing risk behavior, suggesting that the MI-based group may have acquired more risk reduction skills. CONCLUSIONS: Individuals in both study arms reduced risky sexual behaviors after diagnosis with AHI. We found few major differences between study arms during the 6-month follow up period in self-reported sexual behaviors therefore a MI-based intervention may not be needed to trigger behavior change following AHI. However, comparing the MI-based intervention to repeated brief education sessions made it difficult to assess the potential benefit of an MI-based intervention in a setting where standard counseling often consists of one post-test session. Nevertheless, provision of counseling immediately following diagnosis with HIV to support behavior change should remain a priority. TRIAL REGISTRATION: ClinicalTrials.gov NCT01197027.


Subject(s)
HIV Infections/psychology , Motivational Interviewing , Sexual Behavior , Adolescent , Adult , Female , HIV Infections/epidemiology , HIV Infections/transmission , Humans , Malawi/epidemiology , Male , Pilot Projects , Risk Factors , Risk Reduction Behavior , Sexual Partners , Surveys and Questionnaires , Young Adult
17.
Afr J Reprod Health ; 19(4): 50-7, 2015 Dec.
Article in English | MEDLINE | ID: mdl-27337853

ABSTRACT

The copper intrauterine device (IUD) is a safe, long-acting, and effective method of contraception that is under-utilized in many countries, including Malawi. A unique cohort of women who had enrolled in a trial of postpartum IUD use one year earlier gave insights into reasons for using, discontinuing, or not using the IUD. We conducted in-depth interviews with 18 women one year after they participated in a pilot study of a randomized controlled trial of postpartum IUD insertion, and 10 of their male partners. Women and their partners expressed a strong desire for family planning, and perceived numerous benefits of the IUD. However, fear of the IUD was common among successful users and non-users alike. This fear arose from rumours from friends and neighbors who were non-users. How women and their partners responded to this fear affected IUD adoption and continuation. Key themes included (1) Trust in information received from health care providers versus rumours from community members; (2) Partner involvement in IUD decision-making; and (3) Experience with side effects from short-term hormonal contraceptive methods. Broad community education about the IUD's benefits and safety, and proactive counseling to address couples' specific fears, may be needed to increase uptake of the method.


Subject(s)
Contraception/methods , Device Removal , Intrauterine Devices, Copper/statistics & numerical data , Sexual Partners , Adult , Contraception/psychology , Contraception/statistics & numerical data , Device Removal/psychology , Device Removal/statistics & numerical data , Family Planning Services/methods , Family Planning Services/statistics & numerical data , Female , Humans , Malawi/epidemiology , Male , Pilot Projects , Postpartum Period , Sexual Partners/psychology
18.
Cell ; 158(3): 481-91, 2014 Jul 31.
Article in English | MEDLINE | ID: mdl-25065977

ABSTRACT

Development of strategies for induction of HIV-1 broadly neutralizing antibodies (bnAbs) by vaccines is a priority. Determining the steps of bnAb induction in HIV-1-infected individuals who make bnAbs is a key strategy for immunogen design. Here, we study the B cell response in a bnAb-producing individual and report cooperation between two B cell lineages to drive bnAb development. We isolated a virus-neutralizing antibody lineage that targeted an envelope region (loop D) and selected virus escape mutants that resulted in both enhanced bnAb lineage envelope binding and escape mutant neutralization-traits associated with increased B cell antigen drive. Thus, in this individual, two B cell lineages cooperated to induce the development of bnAbs. Design of vaccine immunogens that simultaneously drive both helper and broadly neutralizing B cell lineages may be important for vaccine-induced recapitulation of events that transpire during the maturation of neutralizing antibodies in HIV-1-infected individuals.


Subject(s)
AIDS Vaccines/chemistry , AIDS Vaccines/immunology , Antibodies, Neutralizing/immunology , HIV Antibodies/immunology , HIV-1/physiology , Amino Acid Sequence , B-Lymphocytes/immunology , Immune Evasion , Models, Molecular , Molecular Sequence Data , Mutation , Sequence Alignment , env Gene Products, Human Immunodeficiency Virus/genetics , env Gene Products, Human Immunodeficiency Virus/immunology
19.
J Acquir Immune Defic Syndr ; 65(5): e162-9, 2014 Apr 15.
Article in English | MEDLINE | ID: mdl-24759065

ABSTRACT

BACKGROUND: Patients with newly diagnosed HIV may be part of social networks with elevated prevalence of undiagnosed HIV infection. Social network recruitment by persons with newly diagnosed HIV may efficiently identify undiagnosed cases of HIV infection. We assessed social network recruitment as a strategy for identifying undiagnosed cases of HIV infection. METHODS: In a sexually transmitted infection (STI) clinic in Lilongwe, Malawi, 3 groups of 45 "seeds" were enrolled: STI patients with newly diagnosed HIV, STI patients who were HIV-uninfected, and community controls. Seeds were asked to recruit up to 5 social "contacts" (sexual or nonsexual). Mean number of contacts recruited per group was calculated. HIV prevalence ratios (PRs) and number of contacts needed to test to identify 1 new case of HIV were compared between groups using generalized estimating equations with exchangeable correlation matrices. RESULTS: Mean number of contacts recruited was 1.3 for HIV-infected clinic seeds, 1.8 for HIV-uninfected clinic seeds, and 2.3 for community seeds. Contacts of HIV-infected clinic seeds had a higher HIV prevalence (PR: 3.2, 95% confidence interval: 1.3 to 7.8) than contacts of community seeds, but contacts of HIV-uninfected clinic seeds did not (PR: 1.1, 95% confidence interval: 0.4 to 3.3). Results were similar when restricted to nonsexual contacts. To identify 1 new case of HIV, it was necessary to test 8 contacts of HIV-infected clinic seeds, 10 contacts of HIV-uninfected clinic seeds, and 18 contacts of community seeds. CONCLUSIONS: Social contact recruitment by newly diagnosed STI patients efficiently led to new HIV diagnoses. Research to replicate findings and guide implementation is needed.


Subject(s)
HIV Infections/diagnosis , Social Support , Adolescent , Adult , Female , HIV Infections/epidemiology , Humans , Malawi/epidemiology , Male , Middle Aged , Prevalence , Young Adult
20.
AIDS Behav ; 18(9): 1785-800, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24523007

ABSTRACT

Acute HIV infection (AHI) is a relatively brief period of time when individuals are highly infectious and the opportunity to intervene to prevent forward transmission is extremely limited. HPTN 062 partnered with CHAVI 001 to evaluate the feasibility and acceptability of a motivational interviewing (MI)-based counseling intervention to reduce HIV-transmission risk behaviors among individuals with acute and early HIV infection in Lilongwe, Malawi. Participants were randomized to receive either (1) brief education sessions about HIV and AHI; or (2) the same brief education sessions plus an MI-based counseling intervention called Uphungu Wanga. Although Uphungu Wanga was determined to be feasible and acceptable, few major differences existed between the two arms with regard to acceptability, feasibility, and self-reported sexual behaviors. We therefore conclude that an additional MI-based counseling intervention may not be needed during the short period of AHI. Instead, we recommend that individuals with AHI receive frequent, but brief, counseling immediately after diagnosis and then transition to receiving counseling at less frequent intervals until they can initiate antiretroviral therapy. Other recommendations are provided.


Subject(s)
Counseling , HIV Infections/diagnosis , HIV Infections/prevention & control , Patient Acceptance of Health Care , Risk-Taking , Sexual Partners , Acute Disease , Adolescent , Adult , Feasibility Studies , Female , HIV Infections/psychology , HIV Seropositivity , Humans , Malawi , Male , Motivational Interviewing , Pilot Projects , Process Assessment, Health Care , Program Evaluation , Sexual Behavior/psychology
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