Vaccination is fast becoming a key intervention against the ongoing COVID-19 pandemic. We conducted cross-sectional online surveys to investigate COVID-19 vaccine acceptance across nine Low- and Middle-Income Countries (LMICs; N = 10,183), assuming vaccine effectiveness at 90% and 95%. The prevalence of vaccine acceptance increased from 76.4% (90% effectiveness) to 88.8% (95% effectiveness). Considering a 90% effective vaccine, Malaysia, Thailand, Bangladesh, and five African countries (Democratic Republic of Congo, Benin, Uganda, Malawi, and Mali) had lower acceptance odds compared to Brazil. Individuals who perceived taking the vaccine as important to protect themselves had the highest acceptance odds (aOR 2.49) at 95% effectiveness.Vaccine acceptance was also positively associated with COVID-19 knowledge, worry/fear regarding COVID-19, higher income, younger age, and testing negative for COVID-19. However, chronic disease and female gender reduced the odds for vaccine acceptance. The main reasons underpinning vaccine refusal were fear of side effects (41.2%) and lack of confidence in vaccine effectiveness (15.1%). Further research is needed to identify country-specific reasons for vaccine hesitancy in order to develop mitigation strategies that would ensure high and equitable vaccination coverage across LMICs.

Background: Over 150 000 Malawians have started antiretroviral therapy (ART), in which first-line therapy is stavudine/lamivudine/nevirapine. We evaluated drug resistance patterns among patients failing first-line ART on the basis of clinical or immunological criteria in Lilongwe and Blantyre, Malawi. Methods: Patients meeting the definition of ART failure (new or progressive stage 4 condition, CD4 cell count decline more than 30%, CD4 cell count less than that before treatment) from January 2006 to July 2007 were evaluated. Among those with HIV RNA of more than 1000 copies/ml, genotyping was performed. For complex genotype patterns, phenotyping was performed. Results: Ninety-six confirmed ART failure patients were identified. Median (interquartile range) CD4 cell count, log₁₀ HIV-1 RNA, and duration on ART were 68 cells/μl (23–174), 4.72 copies/ml (4.26–5.16), and 36.5 months (26.6–49.8), respectively. Ninety-three percent of samples had nonnucleoside reverse transcriptase inhibitor mutations, and 81% had the M184V mutation. The most frequent pattern included M184V and nonnucleoside reverse transcriptase inhibitor mutations along with at least one thymidine analog mutation (56%). Twenty-three percent of patients acquired the K70E or K65R mutations associated with tenofovir resistance; 17% of the patients had pan-nucleoside resistance that corresponded to K65R or K70E and additional resistance mutations, most commonly the 151 complex. Emergence of the K65R and K70E mutations was associated with CD4 cell count of less than 100 cells/μl (odds ratio 6.1) and inversely with the use of zidovudine (odds ratio 0.18). Phenotypic susceptibility data indicated that the nucleoside reverse transcriptase inhibitor backbone with the highest activity for subsequent therapy was zidovudine/lamivudine/tenofovir, followed by lamivudine/tenofovir, and then abacavir/didanosine. Conclusion: When clinical and CD4 cell count criteria are used to monitor first-line ART failure, extensive nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor resistance emerges, with most patients having resistance profiles that markedly compromise the activity of second-line ART.

Cabotegravir (CAB) is a novel strand-transfer integrase inhibitor being developed for HIV treatment and prevention. CAB is formulated both as an immediate-release oral tablet for daily administration and as a long-acting injectable suspension (long-acting CAB [CAB LA]) for intramuscular (IM) administration, which delivers prolonged plasma exposure to the drug after IM injection. HIV Prevention Trials Network study 077 (HPTN 077) evaluated the safety, tolerability, and pharmacokinetics of CAB LA in HIV-uninfected males and females at 8 sites in Brazil, Malawi, South Africa, and the United States. HPTN 077 was a double-blind, placebo-controlled phase 2a trial. Healthy individuals age 18–65 years at low HIV risk were randomized (3:1) to receive CAB or placebo (PBO). In the initial oral phase, participants received 1 daily oral tablet (CAB or PBO) for 4 weeks. Those without safety concerns in the oral phase continued and received injections in the injection phase (Cohort 1: 3 injections of CAB LA 800 mg or 0.9% saline as PBO IM every 12 weeks for 3 injection cycles; Cohort 2: CAB LA 600 mg or PBO IM for 5 injection cycles; the first 2 injections in Cohort 2 were separated by 4 weeks, the rest by 8 weeks). The primary analysis included weeks 5 to 41 of study participation, encompassing the injection phase. The cohorts were enrolled sequentially. Primary outcomes were safety and tolerability. Secondary outcomes included pharmacokinetics and events occurring during the oral and injection phases. Between February 9, 2015, and May 27, 2016, the study screened 443 individuals and enrolled 110 participants in Cohort 1 and 89 eligible participants in Cohort 2. Participant population characteristics were as follows: 66% female at birth; median age 31 years; 27% non-Hispanic white, 41% non-Hispanic black, 24% Hispanic/Latino, 3% Asian, and 6% mixed/other; and 6 transgender men and 1 transgender woman. Twenty-two (11%) participants discontinued the oral study product; 6 of these were for clinical or laboratory adverse events (AEs). Of those who received at least 1 CAB LA injection, 80% of Cohort 1 and 92% of Cohort 2 participants completed all injections; injection course completion rates were not different from those in the PBO arm. Injection site reactions (ISRs) were common (92% of Cohort 1 and 88% of Cohort 2 participants who received CAB LA reported any ISR). ISRs were mostly Grade 1 (mild) to Grade 2 (moderate), and 1 ISR event (Cohort 1) led to product discontinuation. Grade 2 or higher ISRs were the only AEs reported more commonly among CAB LA recipients than PBO recipients. Two Grade 3 (severe) ISRs occurred in CAB recipients, 1 in each cohort, but did not lead to product discontinuation in either case. Seven incident sexually transmitted infections were diagnosed in 6 participants. One HIV infection occurred in a participant 48 weeks after last injection of CAB LA: CAB was not detectable in plasma both at the time of first reactive HIV test and at the study visit 12 weeks prior to the first reactive test. Participants in Cohort 2 (unlike Cohort 1) consistently met prespecified pharmacokinetic targets of at least 95% of participants maintaining CAB trough concentrations above PA-IC₉₀, and 80% maintaining trough concentrations above 4× PA-IC₉₀. Study limitations include a modest sample size, a short course of injections, and a low-risk study population. In this study, CAB LA was well tolerated at the doses and dosing intervals used. ISRs were common, but infrequently led to product discontinuation. CAB LA 600 mg every 8 weeks met pharmacokinetic targets for both male and female study participants. The safety and pharmacokinetic results observed support the further development of CAB LA, and efficacy studies of CAB LA for HIV treatment and prevention are in progress. ClinicalTrials.gov Registry: ClinicalTrials.gov Trial number: NCT02178800.

Antiretroviral therapy (ART) in resource-limited settings has expanded in the last decade, reaching >8 million individuals and reducing AIDS mortality and morbidity. Continued success of ART programs will require understanding the emergence of HIV drug resistance patterns among individuals in whom treatment has failed and managing ART from both an individual and public health perspective. We review data on the emergence of HIV drug resistance among individuals in whom first-line therapy has failed and clinical and resistance outcomes of those receiving second-line therapy in resource-limited settings. Resistance surveys among patients initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)–based therapy suggest that 76%–90% of living patients achieve HIV RNA suppression by 12 months after ART initiation. Among patients with detectable HIV RNA at 12 months, HIV drug resistance, primarily due to M184V and NNRTI mutations, has been identified in 60%–72%, although the antiretroviral activity of proposed second-line regimens has been preserved. Complex mutation patterns, including thymidine-analog mutations, K65R, and multinucleoside mutations, are prevalent among cases of treatment failure identified by clinical or immunologic methods. Approximately 22% of patients receiving second-line therapy do not achieve HIV RNA suppression by 6 months, with poor adherence, rather than HIV drug resistance, driving most failures. Major protease inhibitor resistance at the time of second-line failure ranges from 0% to 50%, but studies are limited. Resistance of HIV to first-line therapy is predictable at 12 months when evaluated by means of HIV RNA monitoring and, when detected, largely preserves second-line therapy options. Optimizing adherence, performing resistance surveillance, and improving treatment monitoring are critical for long-term prevention of drug resistance.

Introduction: As a user‐controlled HIV prevention method, oral pre‐exposure prophylaxis (PrEP) holds particular promise for adolescent girls and young women (AGYW). HIV prevention cascades, critical frameworks for the design and evaluation of PrEP programmes, outline the priorities of identifying individuals at greatest HIV risk and motivating them to initiate PrEP through perceived HIV risk. To inform future iterations of these cascades and PrEP delivery for AGYW, the objective of this study was to understand the level of interest in PrEP among AGYW at highest HIV risk, and the potential role of perceived risk in motivating PrEP interest.Methods: Using data from a cohort study of HIV‐negative AGYW in Lilongwe, Malawi (February 2016 to August 2017), we assessed the relationship between epidemiologic HIV risk (risk index developed in a previous analysis) and PrEP interest, and the extent to which perceived risk explains the relationship between HIV risk and PrEP interest. We further aimed to operationalize the pre‐initiation steps of the HIV prevention cascade in the study population.Results: In total, 825 AGYW were included in analyses, of which 43% met the criterion for high epidemiologic HIV risk. While epidemiologic risk scores were positively associated with PrEP interest, high numbers of AGYW both above and below the high‐risk cutoff were very interested in PrEP (68% vs. 63%). Perceived risk partially explained the relationship between HIV risk and PrEP interest; greater epidemiologic HIV risk was associated with high perceived risk, which was in turn associated with PrEP interest. Many more high‐risk AGYW were interested in PrEP (68%) than expressed a high level of perceived HIV risk (26%).Conclusions: These results highlight key relationships between epidemiologic HIV risk, risk perception and interest in PrEP. While risk perception did partially explain the relationship between epidemiologic risk and PrEP interest, there may be other important motivational mechanisms that are not captured in many HIV prevention cascades. The high number of participants with risk scores below the high‐risk cutoff who both expressed high perceived risk and interest in PrEP suggests that demand for PrEP among AGYW may not be well aligned with epidemiologic risk.