Table 1.
Summary of recent clinical trials of HIV prevention
| Author | Intervention | Population | Outcome | Strength of association (95% CI) | Comments |
|---|---|---|---|---|---|
| Selected prevention trials in progress with HIV endpoints | |||||
| HPTN 043 Protocol chair: T.J. Coates | Expanded VCT and bridging to care | South Africa; Tanzania; Zimbabwe; Thailand | Seroprevalence surveys (to estimate HIV incidence) | In progress | Project Accept, community- RCT in progress to test impact of expanded HIV testing and community mobilization on HIV incidence |
| HPTN 052 Protocol chair: S. Cohen | Reduce partner transmission via early ART | Malawi; South Africa; Zimbabwe; India; Thailand; Botswana | Seroconversion in discordant couples | In progress | Individual randomization of discordant couples to assess whether or not early treatment of the HIV+ person reduces HIV infections in partner |
| Control of STDs to reduce HIV acquisition | |||||
| Wawer et al. [18] | Periodic mass therapy for STI | Rakai, Uganda | HIV incidence | RR = 0.97 (0.81–1.16) | Mature HIV epidemic, relatively low rates of curable STIs, high HSV-2 rates, mass periodic STD therapy |
| Kamali et al. [19] | STD syndromic management | Masaka, Uganda | HIV incidence | RR = 0.91 (0.56–1.47) | Mature HIV epidemic, relatively low rates of curable STIs, most infections occurred between regular partners |
| Grosskurth et al. [20] | STD syndromic management | Mwanza, Tanzania | HIV incidence | RR = 0.58 (0.42–0.79) | Syndromic management worked to reduce HIV incidence. High curable STI rates among core transmitters. |
| Celum et al. [21••] | HSV-2 suppression | South Africa; Zimbabwe; Zambia; Peru; USA | HIV incidence | RR = 1.16 (0.83–1.62) | The larger of the two HSV-2 suppression studies, it suggests that nose of acyclovir given to participants may not have been sufficient to reduce HIV susceptibility resulting from HSV-2 infection. |
| Watson-Jones et al. [22•] | Herpes simplex virus type 2 (HSV-2) suppression | Tanzania | HIV incidence | RR = 1.08 (0.64–1.83) | HSV-2 suppression trial showed no benefit for HIV prevention. |
| Adult male circumcision | |||||
| Auvert et al. [23] | Adult male circumcision | Orange Farm, South Africa | HIV incidence | RR = 0.49 (0.28–0.84) | All three trials with remarkably similar results, the strongest effect size of any RCTs for prevention with HIV end points. Male circumcision seen as a powerful tool to reduce HIV transmission; its utility in public health practice now being assessed. |
| Gray et al. [24] | Adult male circumcision | Rakai, Uganda | HIV incidence | RR = 0.47 (0.28–0.78) | |
| Bailey et al. [25] | Adult male circumcision | Kisumu, Kenya | HIV incidence | RR = 0.40 (0.24–0.68) | |
| Behavior change-based interventions | |||||
| Gregson et al. [26] | Integrated community and clinical HIV control• | Manicaland, Zimbabwe | HIV incidence | RR = 1.27 (0.92–1.75) | No notable impact on HIV seroincidence. |
| Jewkes et al. [27••] | Stepping Stones behavioral intervention | South Africa | HIV incidence | RR = 0.95 (0.67–1.35) | A significant decrease in HSV- 2 acquisition was observed as well as a decrease in intimate partner violence suggesting that study impacted HIV-risk behaviors but not HIV transmission. |
| Latkin et al. [28] | Network–oriented peer education | Thailand; USA | Behavioral endpoints† | No significant decrease in risk behaviors (sexual or injection) | Incidence rates were not as high as expected in either arm of the study. It was underpowered to determine the effect of peer education on HIV incidence. |
| Cowan et al. [29] | Multicomponent behavioral intervention in adolescents | Zimbabwe | HIV incidence | In progress | Baseline data suggest that the intervention was implemented prior to onset of sexual activity of adolescents. |
| Pronyk et al. [30] | Microfinance-based structural Intervention | South Africa | HIV incidence, unprotected sex, intimate partner violence | RR = 1.06 (0.66–1.69), RR = 0.89 (0.66–1.19), RR = 1.02 (0.85–1.23) | The study lacked the precision necessary to adequately measure effect size. The number of villages included in the study was determined by feasibility of implementing the intervention, and was not necessarily large enough to detect a small effect size. |
| Padian et al. [31] | Diaphragm | South Africa, Zimbabwe | HIV incidence | RR = 1.05 (0.84–1.32) | Condoms were used extensively in the control arm and not in the intervention arm. This suggests that diaphragm was as efficacious as condoms at preventing HIV acquisition given that risk for acquisition was approximately equal. |
| Microbicide trials | |||||
| Halpern et al. [32] | Microbicide (Cellulose sulfate gel) | Nigeria | HIV Incidence | HR = 0.8 (0.3–1.8) | This trial was suspended early due to data from a parallel trial, which suggested that cellulose sulfate increased risk for HIV acquisition. |
| Abdool Karim et al. [41•] | Microbicide (0.5%PRO 2000 gel) | Malawi, South Africa; Zambia; Zimbabwe; United States | HIV incidence | HR = 0.7 (0.4–1.0) | 30% efficacy suggested borderline statistical significance. |
| Feldblum et al. [33] | Microbicide (0.1% SAVVY gel) | Nigeria | HIV incidence | HR = 1.7 (0.9–3.5) | Trial was halted due to lower-than-expected HIV incidence among participants. There was not adequate power to detect effect of SAVVY gel. |
| Peterson et al. [34] | Microbicide (0.1% SAVVY gel) | Ghana | HIV incidence | HR = 0.88 (0.33–2.27) | Trial was halted due to lower-than-expected HIV incidence among participants. There was not adequate power to detect effect of SAVVY gel. |
| Skoler-Karpoff et al. [35] | Microbicide (Carraguard) | South Africa | HIV incidence | HR = 0.87 (0.69–1.09) | Low levels of reported adherence prevented the trial from having the power needed to detect efficacy of Carraguard. |
| Van Damme et al. [36] | Microbicide (6% cellulose sulfate gel) | Benin; South Africa; India; Uganda | HIV incidence | HR = 1.61 (0.86–3.01) | Safety concerns for this product. |
| Vaccine trials | |||||
| Buchbinder et al. [37••] | Cell-mediated immunity vaccine | North America; South America; Caribbean; Australia | HIV incidence | HR = 1.2 (0.6–2.2) | This trial was halted early because protective efficacy was not observed in males in this cohort. Efficacy assess ment could not be determined in women because of low HIV acquisition rates. |
| Flynn et al. [38] | Recombinant glycoprotein vaccine (VaxGen; bivalent subtype B/B rgp120) | North America | HIV incidence | Vaccine efficacy: 0.06 (317–24) | No vaccine benefits or harms noted. |
| Pitisuttithum et al. [39] | Recombinant glycoprotein vaccine (VaxGen; bivalent subtype B/E rgp120) | Thailand | HIV incidence | Vaccine efficacy: 0.1 (330.8–23.8) | No vaccine benefits or harms noted. |
*
This included: peer education, condom distribution, and syndromic management for sexually transmitted infections.
†
The study was terminated early due to insufficient incidence in study sites. Behavioral data were collected for secondary outcome measures and was used in final analysis. VCT, voluntary counseling and testing.