Non-uptake of viral load testing among people receiving HIV treatment in Gomba district, rural Uganda.

BACKGROUND: Viral load (VL) testing is the gold-standard approach for monitoring human immunodeficiency virus (HIV) treatment success and virologic failure, but uptake is suboptimal in resource-limited and rural settings. We conducted a cross-sectional study of risk factors for non-uptake of VL testing in rural Uganda. METHODS: We conducted a cross-sectional analysis of uptake of VL testing among randomly selected people with HIV (PWH) receiving anti-retroviral treatment (ART) for at least 6 months at all eight primary health centers in Gomba district, rural Uganda. Socio-demographic and clinical data were extracted from medical records for the period January to December 2017. VL testing was routinely performed 6 months after ART initiation and 12 months thereafter for PWH stable on ART. We used descriptive statistics and multivariable logistic regression to evaluate factors associated with non-uptake of VL testing (the primary outcome). RESULTS: Of 414 PWH, 60% were female, and the median age was 40 years (interquartile range [IQR] 31-48). Most (62.3%) had been on ART > 2 years, and the median duration of treatment was 34 months (IQR 14-55). Thirty three percent did not receive VL testing: 36% of women and 30% of men. Shorter duration of ART (≤2 years) (adjusted odds ratio [AOR] 2.38; 95% CI:1.37-4.12; p = 0.002), younger age 16-30 years (AOR 2.74; 95% CI:1.44-5.24; p = 0.002) and 31-45 years (AOR 1.92; 95% CI 1.12-3.27; p = 0.017), and receipt of ART at Health Center IV (AOR 2.85; 95% CI: 1.78-4.56; p < 0.001) were significantly associated with non-uptake of VL testing. CONCLUSIONS: One-in-three PWH on ART missed VL testing in rural Uganda. Strategies to improve coverage of VL testing, such as VL focal persons to flag missed tests, patient education and demand creation for VL testing are needed, particularly for recent ART initiates and younger persons on treatment, in order to attain the third Joint United Nations Program on HIV/AIDS (UNAIDS) 95-95-95 target - virologic suppression for 95% of PWH on ART.

Impact of Male Partner Involvement on Women's Adherence to the Dapivirine Vaginal Ring During a Phase III HIV Prevention Trial.

Although vaginal microbicides for HIV prevention are designed to be female-initiated, male partner influence has been identified as one of the most significant factors impacting women's willingness and ability to use them. As a result, research teams have sought to increase male partner involvement by encouraging disclosure of product use to male partners, promoting male partner engagement in the study through attendance at the study clinic, and helping women to garner male partner support for product use. This paper aims to assess the impact of these three elements of male partner involvement on women's adherence to the dapivirine vaginal ring during MTN-020/ASPIRE, a phase III randomized placebo-controlled clinical trial involving 2629 women in Malawi, South Africa, Uganda, and Zimbabwe. During the study, 64-80% of participants reported disclosure of ring use at each quarterly visit, and 13% reported that their partners had attended the study clinic at some point during the study. At study exit, 66% reported that their partner was supportive, 18% unsupportive, and 17% were unsure. After adjusting for age, site and time in study, women were more likely to have low ring adherence if they had an unsupportive male partner (aRR 1.29, 95% CI 1.03-1.62). Neither disclosure nor clinic attendance directly predicted ring adherence, but disclosure increased the probability of having a supportive partner (aRRR 24.17, 95% CI 16.38-35.66) or an unsupportive partner (aRRR 4.10, 95% CI 2.70-6.24), relative to an unknown level of partner support. Women were also more likely to have a supportive partner if their partner had attended the clinic (aRRR 3.77, 95% CI 1.36-10.42). This study suggests that although the vaginal ring is relatively discreet, lack of support from male partners remains a relevant barrier to use. Though both disclosure and clinic attendance may increase partner support, disclosure may also increase partner opposition. Interventions to reduce male partner opposition are needed to maximize the potential impact of the ring and other PrEP products for HIV prevention.

Risk of HIV-1 acquisition among South African women using a variety of contraceptive methods in a prospective study.

OBJECTIVE: Observational studies have associated use of intramuscular injectable depot medroxyprogesterone acetate (DMPA-IM) with increased risk of HIV-1 acquisition, but limited data are available to assess HIV-1 risk for alternate contraceptive methods. METHODS: Within a randomized trial of the dapivirine vaginal ring for HIV-1 prevention, we assessed HIV-1 incidence by contraceptive method. We limited analyses to participants from South African sites and to women who used DMPA-IM, the alternative injectable norethisterone enanthate, implants, or copper intrauterine devices (IUDs). Contraceptive method was assessed as a time-dependent exposure and multivariate models adjusted for trial randomization arm, age, sexual behaviour, and incident sexually transmitted infections. RESULTS: A total of 95 incident HIV-1 infections were observed: incidence 5.8 (DMPA-IM, n = 52), 6.2 (norethisterone enanthate, n = 28), 1.9 (implant, n = 3), and 4.5 (IUD, n = 12) cases per 100 woman-years. In multivariable models, there were no statistically significant differences between contraceptive methods in the risk of HIV-1 acquisition. However, compared with the IUD, the three hormonal methods each had point estimates near 1 while the implant had risk that was approximately half that of the IUD. When the three hormonal methods were combined, their relative risk compared with IUD was 0.90 (95% confidence interval 0.45-1.76). CONCLUSION: Among women at risk of HIV-1 infections in South Africa, we found no statistically significant differences in HIV-1 incidence by contraceptive method. Implants had the lowest point estimate for HIV-1 incidence, and IUDs had risk comparable with injectable methods in multivariate models. Large, prospective studies are needed to define better the relative HIV-1 risks across different contraceptive methods.

Preventive Misconception and Risk Behaviors in a Multinational HIV Prevention Trial.

BACKGROUND: Some HIV prevention research participants may hold a "preventive misconception" (PM), an overestimate of the probability or level of personal protection afforded by trial participation. However, these reports typically rely upon small, retrospective qualitative assessments that did not use a standardized approach. METHODS: We administered a measure of PM called PREMIS, during Microbicide Trials Network 020-A Study to Prevent Infection with a Ring for Extended Use, a large, multicenter, placebo-controlled, phase III trial evaluating the safety and efficacy of a dapivirine vaginal ring among women at risk for HIV infection in Malawi, South Africa, Uganda, and Zimbabwe. The maximum follow-up period was 2.6 years. RESULTS: One thousand two hundred sixty-one respondents completed PREMIS at their month 3 visit (M3); 2085 at their month 12 visit (M12); and 1010 at both visits. Most participants expressed high expectations of personal benefit (EPB) and that at least one of the rings used in the trial would reduce the risk of getting HIV (expectation of maximum aggregate benefit or EMAB). There was a moderate positive correlation between EPB and EMAB at M3 (r = .43, 95% CI: .37, .47) and M12 (r = .44, 95% CI: .40, .48). However, there was variability among sites in the strength of the relationship. There was no relationship between either expectation variable and condom use, adherence, or HIV infection. CONCLUSIONS: A majority of trial participants expressed some belief that their risk of HIV infection would be reduced by using a vaginal ring, which may signal PM. However, such beliefs were not associated with adherence, condom use, or subsequent HIV infection, and there was variability across sites. Further work is needed to understand these findings.

Implementation of a Novel Adherence Monitoring Strategy in a Phase III, Blinded, Placebo-Controlled, HIV-1 Prevention Clinical Trial.

BACKGROUND: Placebo-controlled HIV-1 prevention trials of pre-exposure prophylaxis (PrEP) have not generally used concurrent measurement of adherence because of the potential risk of unblinding. However, several pre-exposure prophylaxis trials for HIV-1 prevention among women failed to show effectiveness because of low product adherence. Evaluation of product adherence objectively during a study provides the opportunity for strengthening adherence activities at sites having low adherence. METHODS: During MTN-020/ASPIRE, a phase III, placebo-controlled trial of the dapivirine intravaginal ring, we implemented an adherence monitoring system. Monitoring began in quarter 1 (Q1) 2013 and continued through the conclusion of the trial. Blood plasma was collected quarterly and tested for dapivirine concentrations while maintaining blinding among study team members involved in participant management. Dapivirine concentrations >95 pg/mL, reflecting >8 hours of continuous use, were assessed as signaling product use. Study leadership monitored results on a monthly basis and provided feedback to site investigators. Experiences were shared across sites to motivate staff and counsel participants to strive toward higher adherence levels. RESULTS: An upward trend in adherence was observed (P < 0.0001); the proportion of samples from subjects in the active arm with dapivirine >95 pg/mL increased from 63% in Q1 2013 to 84% by Q1 2015. CONCLUSIONS: Ongoing drug level testing as a marker of adherence in MTN-020/ASPIRE demonstrates the feasibility of real-time adherence monitoring while maintaining study blinding at the level of participants, sites, and study leadership. This approach is novel for large-scale effectiveness studies for HIV-1 prevention.

Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women.

BACKGROUND: Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection. METHODS: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of a monthly vaginal ring containing dapivirine, a non-nucleoside HIV-1 reverse-transcriptase inhibitor, involving women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe. RESULTS: Among the 2629 women who were enrolled, 168 HIV-1 infections occurred: 71 in the dapivirine group and 97 in the placebo group (incidence, 3.3 and 4.5 per 100 person-years, respectively). The incidence of HIV-1 infection in the dapivirine group was lower by 27% (95% confidence interval [CI], 1 to 46; P=0.046) than that in the placebo group. In an analysis that excluded data from two sites that had reduced rates of retention and adherence, the incidence of HIV-1 infection in the dapivirine group was lower by 37% (95% CI, 12 to 56; P=0.007) than that in the placebo group. In a post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 years (56%; 95% CI, 31 to 71; P<0.001) but not among those 21 years of age or younger (-27%; 95% CI, -133 to 31; P=0.45), a difference that was correlated with reduced adherence. The rates of adverse medical events and antiretroviral resistance among women who acquired HIV-1 infection were similar in the two groups. CONCLUSIONS: A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01617096 .).